Diversity oriented synthesis of 6-nitro- and 6-aminoquinolones and their activity as alkaline phosphatase inhibitors

Abstract

The novel quinolone derivatives synthesized by cyclization of α,β-ynones with primary amines were shown to be promising TNAP and IAP inhibitors. The mechanism of their formation was studied by the isolation of intermediates.

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Introduction

Alkaline phosphatases (APs) are ubiquitous ectoenzymes widely distributed in nature from bacteria to humans, suggesting their involvement in important physiological processes. Their main functions consist of catalyzing dephosphorylation and transphosphorylation reactions on a broad spectrum of physiological and non-physiological substrates.¹ AP isozymes, encoded by four homologous gene loci, are present in humans and mice. Three of them, known as the placental (PLAP), germ cell (GCAP) and intestinal (IAP) types are tissue-specific with highly restricted expression, while the fourth isozyme, tissue nonspecific AP (TNAP) is present in numerous tissues but particularly abundant in mineralizing tissues, the kidneys and the central nervous system (CNS).²

TNAP is encoded in humans by the AP (alkaline phosphatase, liver/bone/kidney) gene and by the Akp2 (alkaline phosphatase 2) gene in mice, both with 12 exons. In both species, two different transcripts derived from the same coding region have been described. Similar to the rest of the mammalian AP family, TNAP is a homodimeric protein anchored to the cytoplasmic membrane via two GPI moieties.³ Each monomer contains three metallic ions (two zinc molecules and one of magnesium) and one phosphate ion. The central core of each subunit consists of an extended β-sheet flanked by α-helices. Other two identifiable regions are the long N-terminal α-helix and an interfacial flexible loop known as the “crown domain”.⁴

TNAP hydrolyzes extracellular inorganic pyrophosphate (PPi), a potent mineralization inhibitor, to enable the physiological deposition of hydroxyapatite in bones and teeth. Deficiency of TNAP due to gene mutation is responsible for the severe disorder of bones and elevated levels of extracellular PPi.⁵ On the other hand unnecessary deposition of hydroxyapatite together with other forms of calcium phosphate in soft tissues results in over expression of TNAP and hipper calcification in smooth muscle cells of kidney and vessels. It provokes the progress of such serious diseases as end-stage renal disease, idiopathic infantile arterial calcification, ankylosis, osteoarthritis and diabetes. Therefore, there is need to develop potent inhibitors of TNAP and IAP which could be useful as therapeutic agents in the treatment of human atherosclerotic lesions.⁶

By keeping in view the literature findings and our continued interest in the development of potent inhibitors of alkaline phosphatases, we report a short, convenient and efficient method for the catalyst-free one-pot synthesis of 6-nitro-4-quinolones, which could be readily transformed to 6-amino-4-quinolones. The synthesized derivatives were investigated as new a class of inhibitors of alkaline phosphatases: tissue-nonspecific alkaline phosphatase (TNAP) and tissue specific intestinal alkaline phosphatase (IAP). 4-Quinolones are of considerable pharmacological relevance and a number of derivatives are used in the clinic.^7–13 A variety of synthetic strategies have been developed for the synthesis of 4-quinolones.^14–21 A general and modern method for the quinolone synthesis relies on cyclization reactions of ynones.^22–25 Recently we have developed a synthetic concept for the assembly of several fused 4-pyridones, namely, fluorinated 4-quinolones,²⁶ 1,8-naphthyridin-4(1H)-ones,²⁷ benzo[b][1,8]naphthyridin-4(1H)-ones,²⁸ pyrido[2,3-b]quinoxalin-4(1H)-ones²⁸ and thieno[3,2-b]pyridin-4(1H)-ones.²⁹ Most of this work relies on transition metal catalysed cyclizations of alkynes with amines. Herein, we report a convenient catalyst-free one-pot synthesis of 6-nitro-4-quinolones which could be readily transformed to 6-amino-4-quinolones. The synthetic strategy has been previously efficiently applied by Shao at all for the synthesis of N-alkyl-substituted quinolone derivatives via tandem C–N bond-forming process.²² Cacchi's group reported a similar methodology for quinolone synthesis, whereas, the intermediates had to be isolated and CuI catalysis was required.²³ However, the information about ring substitution is still lacking. Herein we report the synthesis of nitro- and amino-substituted quinolones which have, to the best of our knowledge, not been prepared. Moreover, considering that an aryl substituent can improve lipophilicity and action period of a drug we include N-aryl- as well as N-alkyl-derivatives to the new batch. The mechanism of the approach reported herein was studied based on the isolation of intermediates. The nitro- and aminoquinolones prepared in the current study show a considerable activity as TNAP and IAP inhibitors.

Results and discussion

Chemistry

Ynones 6a–d were prepared using a known procedure by Sonogashira cross-coupling reaction of benzoic acid chloride 5 with the appropriate acetylenes using Pd(PPh₃)₂Cl₂ and CuI as catalysts (Table 1 and Scheme 1).^30,31 For the isolation of 6a–d, the use of column chromatography was necessary which resulted in some loss of material, due to partial decomposition on silica. The reaction of ynones 6 with aliphatic and aromatic amines afforded a variety of 6-nitro-4-quinolones 7 (Scheme 1 and Table 2). In general, the cyclization proceeded in lower yields with anilines than with aliphatic amines which are more nucleophilic. The best yields of the desired products were obtained when the reactions were carried out at 120 °C in the presence of potassium carbonate (for aliphatic amines) or potassium phosphate (for aromatic amines) in DMF (reaction time: 6–10 h). The hydrogenation of products 7 under classical conditions (H₂, 10% Pd/C, MeOH) readily afforded 6-amino-4-quinolones 8 in generally good to excellent yields. However, brominated quinolone 7aq underwent reduction of the bromine atom to a hydrogen atom to give the dehalogenated product 8ak.

Table 1 Synthesis of α,β-ynones 6

Entry	6	R^1	Isolated yield, %
1	a	4-(Me)C6H4	76
2	b	C6H5	65
3	c	n-C4H9	75
4	d	n-C5H11	78

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Scheme 1 Synthesis of 6-nitro-4-quinolones 7 and 6-amino-4-quinolones 8. Reagents and conditions: (i), Pd(PPh₃)₂Cl₂ (0.01 equiv.), CuI (0.02 equiv.), THF, NEt₃ (1.3 equiv.), appropriate alkyne (1.3 equiv.), 20 °C, 6 h; (ii), appropriate amine (1.7 equiv.), K₂CO₃ (2 equiv.), DMF, 120 °C, 7 h; (iii), H₂, 10% Pd/C, MeOH, 20 °C, 4 h.

Table 2 Synthesis of 6-nitro-4-quinolones 7 and 6-amino-4-quinolones 8

Substrate 6	Amine	Products 7^a, isolated yield	Products 8^c, isolated yield
a Standard conditions for aliphatic amines: 1.7 equiv. appropriate amine, 2 equiv. K2CO3, DMF, 120 °C, 6–8 h.b Alternative conditions for aromatic amines: 1.7 equiv. primary amine, 2 equiv. K3PO4, DMF, 120 °C, 6–10 h.c Standard conditions: methanol, 0.1 equiv. 10% Pd/C, H2, 20 °C, 4–5 h.d Yield of the product 8ak obtained from substrate 7ak.e Yield of the product 8ak obtained from the substrate 7aq.f Experiment was not performed.g Specific conditions for the isolation of 9a and 9b: 1.7 equiv. of the appropriate amine, 2 equiv. KF, DMF, 120 °C, 10 h.h Specific conditions for isolation of 9c and 10a: 1.7 equiv. appropriate amine, 2 equiv. KF, DMF, 120 °C, 4 h.i Specific conditions for isolation of 9d and 10b: 1.7 equiv. cyclohexylamine, 2 equiv. KF, DMF, 60 °C, 10 h. In this case 7 was not formed.
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a			^f
6a
6a
6a			^f
6a
6a			^f
6b			^f
6b
6b
6b
6b
6b
6b			^f
6c			^f
6c			^f
6c			^f
6c		^i	^f
6d

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During the optimization of the conditions of the cyclization, we were able to isolate side-products 9 and 10 (Scheme 2). The quantity of these compounds strongly depends on the conditions (see legend of Table 2). The formation of products 9 can be explained by reaction of 6 with two molecules of the amine, i.e. conjugate addition to the ynone and nucleophilic substitution at the arene. Products 10 are formed by conjugate addition of the amine to the alkynone moiety. Under the standard conditions applied for the synthesis of quinolones 7, side-products 9 and 10 were formed only in very small quantities (1–2%). However, 9a–d could be isolated and spectroscopically characterized when the reaction was carried out at lower temperature. Reduction of the reaction time during the synthesis of nitroquinolone derivatives allowed us to isolate intermediates 10a and 10b. In general, the yields of unwanted side-products 9 and 10 increased when potassium fluoride was employed instead of standard K₂CO₃ and K₃PO₄.

Scheme 2 Side-products 9 and 10. Yields of isolated compounds obtained in reaction conditions specified in footnotes g, h, and i of Table 2.

To study the mechanism of the cyclization, we heated compounds 10 under standard conditions (footnote a of Table 2). In fact, products 10a and 10b were converted into quinolones 7. In contrast, heating of compound 9 resulted in no conversion. This result suggests that mono-adducts 10a and 10b can be regarded as intermediates of the cyclization reaction, whereas bis-adducts 9 are by-products and are not involved in the reaction mechanism. Therefore, it can be anticipated that the first step of the formation of 7 proceeds by conjugate addition of the amine to the ynone. In the second step, the cyclization takes place by an intermolecular nucleophilic substitution of the chlorine atom of the benzene moiety. The leaving group is strongly activated by the nitro group located in para position. The suggested mechanism is also confirmed by the following observation: the reaction of N-methylaniline with ynone 6 afforded product 11 in good yield (Scheme 3). This product cannot undergo a further cyclization because of the complete substitution of the nitrogen atom. The high yield of 11 suggests that the first attack of the amine occurs at the ynone and not at the arene moiety of 6. Indeed, related reactions were previously reported.²³

Scheme 3 Reaction of 6a with a secondary amine. Reagents and conditions: (i) 1.7 equiv. N-methylaniline, 2 equiv. K₃PO₄, DMF, 120 °C, 8 h.

The cyclization of 6a with aliphatic diamines afforded bis(4-quinolones) 12a and 12b in good yields (Scheme 4). The synthesis of bis(quinolones) containing two quinolone fragments using 6-amino-4-quinolones 8 as starting materials was next studied. The reaction of 8ai and 8aj with ynone 6a afforded the desired bis(quinolones) 13a and 13b, albeit, in rather low yield. The low yields can be explained by the low nucleophilicity of the amino group of 6-aminoquinolones 8.

Scheme 4 Bis(quinolones) 12a, b and two-unit chains of 4-quinolones 13a, b.

The structures of 4-nitroquinolones 7ab, 7ac, and 7bd were independently confirmed by X-ray crystallographic analyses (Fig. 1–3).³²

Fig. 1 Molecular structure of compound 7ab.

Fig. 2 Molecular structure of compound 7ac.

Fig. 3 Molecular structure of compound 7bd.

The reaction of 6-aminochromone 8ab with CuBr₂ and t-butyronitrite afforded dibrominated quinolone 14 in 72% yield. The Suzuki–Miaura reaction of 14 with 4-ethylphenylboronic acid afforded diarylated quinolone 15, albeit, in low yield. Due to the low yield, Pd catalyzed cross-coupling reactions of dibromide 14 were not further studied. In contrast, the Suzuki–Miaura reaction of known 3,6-dibromochromone gave product 16 in 48% yield (Scheme 5). The structures of 15 and 16 were independently confirmed by X-ray crystal structure analyses (Fig. 4 and 5). The measured crystal of 15 contains small amounts (about 3%) of the 6-aryl-3-bromo derivative, which was formed as an intermediate product during the Suzuki–Miaura coupling reaction.

Scheme 5 Modification of the C-6 and C-3 positions in 4-quinolone and chromone. Reagents and conditions: (i) t-BuNO₂, CuBr₂, acetonitrile; (ii) 8ab or 3,6-dibromo-4H-chromen-4-one, 1.2 equiv. of aryl boronic acid, 0.1 equiv. of Pd(PPh₃)₄, 10 equiv. K₂CO₃, toluene/H₂O/MeOH = 5.5/1/1.5, 90 °C, 4 h.

Fig. 4 Molecular structure of compound 15.

Fig. 5 Molecular structure of compounds 16.

Alkaline phosphatase inhibition assay

We tested the activity of 6-nitroquinolones 7 and 6-aminoquinolones 8 as inhibitors of bovine kidney alkaline phosphatase enzyme (TNAP) and intestinal alkaline phosphatase enzyme (IAP). A chemiluminescent substrate, CDP-star, was used for the determination of alkaline phosphatase activity. The conditions for the assay were optimized with slight modifications of the previously used spectrophotometric method.³³

Synthesized quinoline derivatives were analysed against two isozymes of alkaline phosphatase, i.e. b-TNAP and c-IAP. By varying the substituents located at the heterocyclic core structure, various derivatives were synthesized, including 6-amino quinoline and 6-nitro quinolones. All these derivatives were active against b-TNAP and c-IAP with some exceptions. All nitroquinolones 7 were active against TNAP and the inhibitory values were in the range of IC₅₀ ± SEM = 1.43 ± 0.08 to 134.1 ± 3.66 μM. Besides the inhibition, the selectivity represents an important issue. Among these, 7ba was found to be a very potent and, in addition, a selective inhibitor of b-TNAP having an inhibitory value of IC₅₀ ± SEM = 6.34 ± 0.23 μM. This compound showed a threefold higher potential as compared to the reference standard used in the assay, i.e. Levamisole with a value of IC₅₀ ± SEM = 19.21 ± 0.001 μM. A detailed study of the structure revealed that the selective activity might be due to the presence of the 3,4-(dimethoxyphenyl)ethyl substituent located at the nitrogen and an aryl group located at position 2 of the 6-nitroquinolone ring. Compound having an alkyl group located at position 2 of the quinolone moiety, i.e. derivatives 7cb and 7db, displayed a significant inhibitory activity against b-TNAP, with IC₅₀ ± SEM = 1.43 ± 0.08 and 1.51 ± 0.006 μM, respectively. Compounds having an alkyl substituent located at the nitrogen atom, such as 7ab, 7ad, 7ag and 7aj, are inactive or show a low activity against TNAP. All these derivatives remain active against c-IAP, except two compounds. All 6-nitroquinolones displayed inhibitory activity against C-IAP in the range of IC₅₀ ± SEM = 1.38 ± 0.01 to 132.4 ± 2.45 μM. Derivative 7af, containing a cyclohexyl and a tolyl substituent, shows a high activity against both TNAP and C-IAP with IC₅₀ ± SEM = 1.74 ± 0.002 and 1.75 ± 0.009 μM, respectively. Compounds bearing aryl substituents at position 2 display a significant activity against c-IAP, irrespective of the type of substituent located at position 1.

All aminoquinolones displayed a remarkable activity against b-TNAP in the range of IC₅₀ ± SEM = 1.14 ± 0.65 to 78.1 ± 1.56 μM. Most of these compounds were found to be selective inhibitors of b-TNAP, however, some compounds were also active against c-IAP. A detailed study of the structure suggested that all compounds showing a potent activity against TNAP contain an aromatic ring located at position 2 of the quinolone. The presence of an alkyl group reduced the bioactivity. The activity against c-IAP were in the range of IC₅₀ ± SEM = 0.443 ± 0.002 to 176.4 ± 2.34 μM. The structure–activity relationship elucidated that the presence of a bulky group or of a hydrophobic group located at the nitrogen atom results in a significant increase of the inhibitory effect against c-IAP. Compound 8an has been found to be the most potent derivative showing a IC₅₀ value of IC₅₀ ± SEM = 0.443 ± 0.002.

Two compounds of the series, i.e. 8ah and 16, contain a chromene substructure. These compounds were found to be more active against c-IAP than against b-TNAP. The inhibitory values against c-IAP were IC₅₀ ± SEM = 0.797 ± 0.01 and 1.41 ± 0.08 μM, respectively. In contrast, against b-TNAP, these compound showed IC₅₀ ± SEM = 5.84 ± 0.99 to 40.9 ± 1.23 μM.

Conclusions

A diversity orientated synthesis of biologically relevant novel 6-nitro- and 6-amino-4-quinolones was reported. The products were obtained in good to excellent yields. The operational simplicity of the methodology is remarkable. The methodology has a broad applicability with regard to the scope. A variety of products show a high and selective inhibition of enzyme alkaline phosphatase.

Experimental section

General information

NMR spectra were recorded on Bruker Avance 250 (250 MHz), Brucker Avance 300 (300 MHz) and Brucker Avance 500 (500 MHz). Chemical shifts (ppm) are given relative to solvent: references for CDCl₃ were 7.26 ppm (¹H NMR) and 77.16 ppm (¹³C NMR); references for DMSO-d₆ were 2.54 ppm (¹H NMR) and 39.50 ppm (¹³C NMR). Multiplets were assigned as s (singlet), d (doublet), t (triplet), q (quartet), p (pentet), m (multiplet), br s (broad singlet). All measurements were carried out at room temperature unless otherwise stated. IR spectra were recorded on a Nicolet 6700 FT-IR spectrometer (ATR). A wavelength is given in cm⁻¹. Abbreviations: s = strong; m = middle; w = weak. Melting points were measured on Stanford Research Systems oder Micro-Hot-Stage GalenTM III Cambridge Instruments. Abbreviation: Mp. The melting points were not corrected. Mass spectra were obtained on a Hewlett-Packard HP GC/MS 5890/5972 instrument (EI, 70 eV) by GC inlet, on a MX-1321 and Finnigan MAT 95 XP instruments (EI, 70 eV) by direct inlet. The data are given as mass units per charge (m/z). Column chromatography was performed on silica gel (63–200 mesh, Merck). Chemical yields refer to pure isolated substances. The CDP-Star chemiluminescent substrate was obtained from Sigma Aldrich while other chemicals used in the assay were of analytical grade.

Alkaline phosphatase inhibition assay

The diethanolamine (8 M DEA (pH 9.8), 2.5 mM MgCl₂ and 0.05 mM ZnCl₂) was used as assay buffer. All the compounds were tested at the final concentration of 0.2 mM with the final DMSO 1% (v/v). The total volume of 50 μL contained 10 μL of a tested compound, followed by the addition of 20 μL of TNAP (1 : 800 times diluted (0.8 units per mL) enzyme in assay buffer). The mixture was pre-incubated for 3–5 minutes at 37 °C and luminescence was observed as pre-read using microplate reader (BioTek FLx800, Instruments, Inc. USA). Then, 20 μL of CDP-star (final concentration of 110 μM) was added to initiate the reaction and the assay mixture was incubated again for 15 min at 37 °C. The change in the luminescence was observed as after-read. The activity of each compound was compared with total activity control (without any inhibitor). Levamisole (2 mM per well) was used as a positive control. For potentially active compounds, exhibited over 50% inhibition, full concentration inhibition curves were produced. For this purpose 6 to 8 serial dilutions of each compound (200 μM to 20 nM) were prepared in assay buffer and their dose response curves were obtained by assaying each inhibitor concentration against TALP using the above mentioned reaction conditions. All experiments were repeated three times. The Cheng Prusoff equation was used to calculate the IC₅₀ values (Table 3), determined by the non-linear curve fitting program PRISM 5.0 (GraphPad, San Diego, California, USA).

Table 3 Tissue non-specific alkaline phosphatase (b-TNAP) and intestinal alkaline phosphatase (c-IAP) inhibition data for the synthesized compounds

Codes	b-TNAP	c-IAP	Codes	b-TNAP	c-IAP
	IC50^a (μM) ± SEM or (% inhibition)^b	IC50^a (μM)± SEM or (% inhibition)^b		IC50^a (μM) ± SEM or (% inhibition)^b	IC50^a (μM)± SEM or (% inhibition)^b
a The IC50 is the concentration at which 50% of the enzyme activity is inhibited.b The % inhibition of the enzyme activity caused by 0.2 mM of the tested compounds.
7aa	11.2 ± 1.11^a	19.1 ± 0.76^a	8aa	31.9 ± 1.23^a	2.63 ± 0.99^a
7ab	132.6 ± 1.78^a	48.65%^b	8ab	9.25 ± 0.88^a	23.3 ± 1.54^a
7ac	17.9 ± 2.45^a	4.75 ± 0.45^a	8ac	2.87 ± 0.04^a	45.21%^b
7ad	59.6 ± 2.67^a	31.2 ± 2.11^a	8ad	1.77 ± 0.001^a	34.5 ± 1.23^a
7ae	12.5 ± 1.06^a	23.1 ± 1.09^a	8ae	78.1 ± 1.56^a	45.67%^b
7af	1.74 ± 0.002^a	1.75 ± 0.009^a	8af	37.4 ± 2.33^a	35.98%^b
7ag	43.2 ± 3.55^a	10.9 ± 0.33^a	8ag	9.74 ± 1.07^a	4.36 ± 0.21^a
7ah	4.56 ± 0.33^a	5.88 ± 0.13^a	8ah	5.84 ± 0.99^a	0.797 ± 0.01^a
7ai	22.9 ± 3.11^a	4.96 ± 0.98^a	8ai	30.4 ± 1.34^a	11.4 ± 1.21^a
7aj	11.6 ± 0.22^a	132.4 ± 2.45^a	8ak	4.33 ± 0.66^a	39.8 ± 1.34^a
7ak	21.9 ± 2.11^a	1.51 ± 0.002^a	8am	7.59 ± 0.56^a	34.56%^b
7al	4.71 ± 0.34^a	10.3 ± 1.56^a	8an	1.98 ± 0.01^a	0.443 ± 0.002^a
7am	20.4 ± 1.98^a	54.7 ± 2.15^a, 34.56%^b	8ap	49.1 ± 2.15^a	16.6 ± 0.76^a
7an	3.13 ± 0.22^a	3.32 ± 0.08^a	8ba	6.61 ± 0.89^a	21.34%^b
7ao	2.91 ± 0.11^a	11.3 ± 0.65^a	8bc	4.45 ± 0.03^a	4.71 ± 0.43^a
7ap	12.8 ± 1.21^a	4.26 ± 0.33^a	8bd	3.24 ± 0.02^a	13.2 ± 0.97^a
7aq	11.8 ± 0.98^a	73.3 ± 1.76^a	8be	10.2 ± 1.76^a	48.98%^b
7ba	6.34 ± 0.23^a	12.33^b	8bf	17.4 ± 1.09^a	154.2 ± 1.34^a
7bc	4.17 ± 0.21^a	54.3 ± 0.43^a	8bg	2.13 ± 0.03^a	48.65%^b
7bd	11.8 ± 0.11^a	10.7 ± 0.44^a	8ca	4.16 ± 0.23^a	18.1 ± 1.21^a
7be	9.72 ± 0.99^a	23.6 ± 1.33^a	8da	29.7 ± 2.11^a	176.4 ± 2.34^a
7bf	7.62 ± 0.22^a	15.4 ± 0.11^a	12a	1.14 ± 0.65^a	1.24 ± 0.04^a
7bg	3.98 ± 0.06^a	2.87 ± 0.02^a	12b	4.17 ± 0.99^a	5.91 ± 0.66^a
7bh	3.39 ± 0.001^a	1.59 ± 0.91^a	13a	2.55 ± 0.03^a	10.7 ± 0.98^a
7ca	134.1 ± 3.66^a	6.44 ± 0.99^a	13b	9.46 ± 1.23^a	0.531 ± 0.01^a
7cb	1.43 ± 0.08^a	21.9 ± 0.87^a	14	6.06 ± 1.01^a	4.75 ± 0.09^a
7cd	11.2 ± 1.23^a	8.32 ± 1.22^a	16	40.9 ± 1.23^a	1.41 ± 0.08^a
7db	1.51 ± 0.006^a	1.38 ± 0.01^a	17a	10.1 ± 1.12^a	8.26 ± 1.45^a
Levamisole	19.21 ± 0.001^a	—
L-Phenyl alanine	—	80.21 ± 0.001^a

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General procedure for the synthesis of 6

A predried Schlenk tube was purged with inert gas, furnished with a mixture of 2-chloro-5-nitrobenzoyl chloride 5 (1.00 g, 1 equiv.), Pd(PPh₃)₂Cl₂ (32 mg, 0.01 equiv.), CuI (18 mg, 0.02 equiv.) and closed with a septum stopper. Then extra dry THF (20 mL) and Et₃N (0.82 mL, 1.3 equiv.) were added to the mixture. The Schlenk tube was threefold refilled with inert gas. Then the acetylene (1.3 equiv.) was added dropwise within 10 min with stirring. The reaction mixture was stirred for 6 h at room temperature. After the consumption of the starting material (TLC control) the solvent was evaporated under reduced pressure. In the case of solid character of the residue, the latter was washed with water, filtered and recrystallized from a mixture of n-heptane and ethanol (2 : 1). In case of an oily character of the residue, the crude reaction mixture was diluted with dichloromethane and washed with water. The organic layer was separated and dried over Na₂SO₄, filtered and purified by column chromatography (silica gel, chloroform/heptane, 3 : 1).

1-(2-Chloro-5-nitrophenyl)-3-p-tolylprop-2-yn-1-one (6a). Brown crystals, yield 76%. Mp 141–143 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 2.44 (s, 3H, –CH₃), 7.27 (d, 2H, ³J = 8.0 Hz, –Tol), 7.59 (d, 2H, ³J = 8.0 Hz, –Tol), 7.70 (d, 1H, ³J = 8.7 Hz, Ar), 8.33 (dd, 1H, ³J = 8.7 Hz, ⁴J = 2.7 Hz, Ar), 8.95 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (300.13 MHz, CDCl₃): δ = 21.80 (–CH₃, –Tol) 87.64 (C, –CC–Tol), 96.91 (C, –CC–Tol), 116.11 (C, Tol), 127.08 (CH, Ar), 127.18 (CH, Ar), 129.62 (2CH, Tol), 132.68 (CH, Ar), 133.40 (2CH, Tol), 136.67 (C-1, Ar), 140.00 (–CO–), 142.55 (C, Tol), 146.25 (C-2, Ar), 174.20 (C-5, Ar). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3108 (w), 2919 (w), 2202 (s), 1602 (s), 1519 (s), 1396 (m), 1342 (s), 1297 (s), 1248 (m), 1176 (m), 1074 (s), 1037 (m), 924 (m), 819 (s), 736 (s), 631 (m), 570 (m), 539 (m). MS (GC, 70 eV): m/z (%) = 301 (M₁⁺, 14), 299 (M₂⁺, 41), 271 (25), 189 (18), 143 (100), 115 (10), 89 (9). HRMS (ESI): calcd for C₁₆H₁₀³⁵ClNO₃: 299.0338, found: 299.0344; calcd for C₁₆H₁₀³⁷ClNO₃: 301.0314, found: 301.0312.

1-(2-Chloro-5-nitrophenyl)-3-phenylprop-2-yn-1-one (6b). Brown crystals, yield 65%. Mp 110–112 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 7.34–7.48 (m, 2H, Ph), 7.49–7.57 (m, 1H, Ph), 7.64–7.70 (m, 2H, Ph + 1H, Ar), 8.32 (dd, 1H, ³J = 8.8 Hz, ⁴J = 2.7 Hz, Ar), 8.93 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (250.13 MHz, CDCl₃): δ = 87.62 (C, –CC–Ph), 96.12 (C, –CC–Ph), 119.28 (C, Ph), 127.23, 127.27 (2CH, Ar), 128.85 (2CH, Ph), 131.60 (CH, Ph), 132.77 (CH, Ar), 133.38 (2CH, Ph), 136.58 (C-1, Ar), 140.11 (–CO–), 146.32 (C-2, Ar), 174.24 (C-5, Ar). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3107 (s), 2189 (m), 1651 (w), 1604 (m), 1573 (m), 1521 (m), 1486 (m), 1440 (m), 1349 (w), 1309 (w), 1270 (m), 1251 (m), 1198 (m), 1107 (m), 1077 (w), 997 (w), 897 (w), 839 (w), 810 (m), 761 (w), 735 (w), 688 (w), 627 (w), 594 (w), 537 (w). MS (GC, 70 eV): m/z (%) = 286 (M⁺, 29), 257 (26), 176 (21), 129 (100), 75 (21). HRMS (ESI): calcd for C₁₅H₈ClNO₃: 286.0266, found: 286.0267.

1-(2-Chloro-5-nitrophenyl)hept-2-yn-1-one (6c). Yellow oil, yield 75%. ¹H NMR (300.13 MHz, CDCl₃): δ = 0.95 (t, 3H, ³J = 7.3 Hz, –C₃H₆CH₃), 1.42–1.56 (m, 2H, –CH₂CH₂CH₂CH₃), 1.59–1.72 (m, 2H, –CH₂CH₂–CH₂CH₃), 2.51 (t, 2H, ³J = 7.0 Hz, –CH₂C₃H₇), 7.64 (d, 1H, ³J = 8.8 Hz, Ar), 8.27 (dd, 1H, ³J = 8.8 Hz, ⁴J = 2.7 Hz, Ar), 8.84 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (300.13 MHz, CDCl₃): δ = 13.40 (–CH₃, –n-But), 19.00, 22.01, 29.42 (3CH₂), 80.33 (C, –CC–n-Bu), 100.16 (C, –CC–n-Bu), 126.99, 127.33, 132.65 (3CH, Ar), 136.51 (C-1, Ar), 139.94 (–CO–), 146.14 (C-2, Ar), 174.35 (C-5, Ar). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2958 (m), 2871 (w), 2209 (m), 1660 (m), 1606 (m), 1524 (s), 1460 (m), 1344 (s), 1231 (s), 1053 (m), 914 (m), 835 (m), 738 (s), 533 (m). MS (GC, 70 eV): m/z (%) = 265 (M⁺, 1), 225 (23), 224 (11), 223 (71), 186 (33), 185 (12), 184 (100), 178 (11), 148 (15), 140 (10), 138 (28), 113 (21), 110 (29), 109 (70), 81 (32), 79 (47), 75 (26), 74 (16), 66 (22), 63 (14), 53 (30), 43 (33), 41 (42), 39 (19). HRMS (ESI): calcd for C₁₃H₁₂ClNO₃: 265.0500, found: 265.0506.

1-(2-Chloro-5-nitrophenyl)oct-2-yn-1-one (6d). Yellow oil, yield 78%. ¹H NMR (300.13 MHz, CDCl₃): δ = 0.94 (t, 3H, ³J = 7.2 Hz, –(CH₂)₄CH₃), 1.34–1.50 (m, 4H, –(CH₂)₂(CH₂)₂CH₃), 1.70 (p, 2H, ³J = 7.2 Hz, –CH₂CH₂C₃H₇), 2.54 (t, 2H, ³J = 7.1 Hz, –CH₂C₄H₉), 7.67 (d, 1H, ³J = 8.8 Hz, Ar), 8.30 (dd, 1H, ³J = 8.8 Hz, ⁴J = 2.7 Hz, Ar), 8.87 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (250.13 MHz, CDCl₃): δ = 13.79 (–C₄H₈–CH₃), 19.29, 22.04, 27.12, 31.03 (4CH₂), 80.34 (C, –COCC–), 100.22 (C, –COCC–), 127.00, 127.33, 132.65 (3CH), 136.52 (C-1, Ar), 139.95 (–CO–), 146.14 (C-2, Ar), 174.36 (C-5, Ar). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2930 (m), 2209 (s), 1660 (s), 1605 (s), 1525 (s), 1459 (m), 1344 (s), 1230 (s), 1130 (m), 1051 (s), 839 (m), 738 (s), 534 (m). MS (GC, 70 eV): m/z (%) = 279 (M⁺, 2), 264 (12), 262 (11), 244 (16), 236 (10), 223 (16), 198 (12), 186 (36), 184 (100), 178 (10), 148 (13), 140 (12), 138 (31), 123 (14), 113 (19), 110 (21), 95 (55), 80 (19), 79 (16), 75 (19), 74 (12), 67 (34), 66 (18), 63 (10), 55 (40), 53 (14), 41 (36), 39 (15), 29 (28). HRMS (ESI-TOF): calcd for C₁₄H₁₄ClNO₃: 279.0656, found: 279.0662.

General procedure for the synthesis of 7

Under a constant flow of an inert gas a pressure tube was charged with a magnetic stirrer, appropriate α,β-ynone 6 (450 mg, 1 equiv.), K₂CO₃ (for aliphatic amines) or K₃PO₄ (for aromatic amines) (2 equiv.), extra dry dimethylformamide (6 mL) and appropriate amine (1.7 equiv.). After the consumption of the starting material (6–10 h; TLC control) at 120 °C the reaction mixture was cooled to room temperature. The solvent was evaporated and the residue was recrystallized from an i-PrOH or purified by a column chromatography (silica gel, heptane/ethyl acetate (5 : 1 to 1 : 1); R_f ≈ 0.30–0.45).

1-(3,4-Dimethoxyphenethyl)-6-nitro-2-p-tolylquinolin-4(1H)-one (7aa). Brown crystals. 51%. Mp 163–165 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 2.43 (s, 3H, –CH₃, –Tol), 2.84 (t, 2H, ³J = 7.2 Hz, –CH₂–CH₂–Ar′), 3.59 (s, 3H, –OCH₃), 3.73 (s, 3H, –OCH₃), 4.37 (t, 2H, ³J = 7.2 Hz, –CH₂–CH₂Ar′), 6.07 (s, 1H, COCH=), 6.27 (d, 1H, ⁴J = 1.9 Hz, Ar′), 6.39 (dd, 1H, ³J = 8.1 Hz, ⁴J = 1.9 Hz, Ar′), 6.79 (d, 1H, ³J = 8.1 Hz, Ar′), 7.28 (d, 2H, ³J = 7.9 Hz, –Tol), 7.34 (d, 2H, ³J = 7.9 Hz, –Tol), 8.28 (d, 1H, ³J = 9.5 Hz, Ar), 8.56 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.9 Hz, Ar), 9.00 (d, 1H, ⁴J = 2.9 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 20.83 (CH₃, –Tol), 33.43, 49.84 (2CH₂), 55.07, 55.56 (2-OCH₃), 111.77, 112.06, 113.08 (3CH), 120.07 (C), 120.66, 121.70 (2CH), 126.01 (C), 126.16 (CH), 128.24, 129.12 (4CH, –Tol), 129.34, 132.10, 139.28, 142.65 (4C), 144.11 (CH), 147.65, 148.64, 156.05, 174.93 (4C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3087 (w), 2952 (w), 1637 (s), 1519 (s), 1470 (s), 1334 (s), 1265 (m), 1148 (m), 1033 (m), 832 (m), 746 (m), 626 (w). MS (GC, 70 eV): m/z (%) = 444 (M⁺, 17), 443 (13), 427 (91), 414 (39), 398 (12), 293 (32), 263 (23), 247 (36), 177 (21), 165 (11), 151 (100), 131 (27), 107 (14). HRMS (ESI): calcd for C₂₆H₂₄N₂O₅: 444.1679, found: 444.1685.

1-(4-Methoxybenzyl)-6-nitro-2-p-tolylquinolin-4(1H)-one (7ab). Yellow crystals, yield 83%. Mp 245–247 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 2.39 (s, 3H, CH₃, –Tol), 3.77 (s, 3H, –OCH₃), 5.27 (s, 2H, –CH₂–), 6.36 (s, 1H, –COCH–), 6.83 (d, 2H, ³J = 8.8 Hz, Ar′), 6.91 (d, 2H, ³J = 8.8 Hz, Ar′), 7.21 (d, 2H, ³J = 8.3 Hz, –Tol), 7.25 (d, 2H, ³J = 8.3 Hz, –Tol + CDCl₃), 7.45 (d, 1H, ³J = 9.4 Hz, Ar), 8.27 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.8 Hz, Ar), 9.28 (d, 1H, ⁴J = 2.8 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 21.29 (–CH₃, –Tol), 52.22 (–CH₂–), 55.26 (–OCH₃), 114.43 (CH), 114.64 (2CH), 118.89, 123.28, 126.13 (3CH), 126.56 (2CH), 126.84, 127.06 (2C), 127.89, 129.53 (4CH), 131.81, 140.38, 143.27, 144.59, 156.35, 159.25, 176.55 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2951 (w), 1634 (s), 1515 (s), 1472 (s), 1332 (s), 1253 (s), 1171 (m), 1114 (m), 1027 (m), 911 (m), 801 (s), 744 (m), 634 (m). MS (GC, 70 eV): m/z (%) = 400 (M⁺, 5), 122 (40), 121 (100), 77 (11). HRMS (ESI): calcd for C₂₄H₂₀N₂O₄: 400.1417, found: 400.1423.

(R)-6-Nitro-1-(1-phenylethyl)-2-p-tolylquinolin-4(1H)-one (7ac). Beige crystals, yield 87%. Decompose near to 365 °C. ¹H NMR (500.13 MHz DMSO-d₆): δ = 2.01 (d, 3H, ³J = 7.0 Hz, –CHCH₃Ph), 2.39 (s, 3H, CH₃, –Tol), 5.74 (q, 1H, ³J = 7.0 Hz, –CHCH₃Ph), 6.19 (s, 1H, –COCH=), 7.31–7.41 (m, 3H, Ar′ + 4H, –Tol), 7.47 (d, 1H, ³J = 9.6 Hz, Ar), 7.57 (d, 2H, ³J = 5.8 Hz, Ar′), 8.20 (dd, 1H, ³J = 9.6 Hz, ⁴J = 2.9 Hz, Ar), 8.95 (d, 1H, ⁴J = 2.9 Hz, Ar). ¹³C NMR (500.13 MHz, DMSO-d₆): δ = 16.89, 20.81 (2CH₃), 58.77 (CH, –CHMePh), 113.38 (CH, –COCH–), 121.65, 121.73, 124.96 (3CH), 125.34 (2CH), 127.18 (C), 127.45 (2CH), 129.07 (3CH), 129.60 (2CH), 132.64, 139.22, 139.61, 142.31, 142.85, 156.79, 174.96 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3084 (w), 1633 (s), 1513 (m), 1471 (s), 1331 (s), 1238 (m), 1085 (m), 911 (m), 864 (s), 835 (s), 749 (s), 695 (s), 652 (m). MS (GC, 70 eV): m/z (%) = 384 (M⁺, 2), 280 (15), 105 (100). HRMS (ESI): calcd for C₂₄H₂₀N₂O₃: 384.1468, found: 384.1461.

1-Heptyl-6-nitro-2-p-tolylquinolin-4(1H)-one (7ad). Brown crystals. 72%. Mp 133–135 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.83 (t, 3H, ³J = 7.0 Hz, –(CH₂)₆CH₃), 1.12 (m, 8H, –(CH₂)₂(CH₂)₄CH₃), 1.60 (p, 2H, ³J = 6.5 Hz, –CH₂CH₂C₅H₁₁), 2.45 (s, 3H, –CH₃, –Tol), 4.15 (t, 2H, ³J = 7.9 Hz, –CH₂C₆H₁₃), 6.12 (s, 1H, –COCH=), 7.42 (d, 2H, ³J = 7.45 Hz, –Tol), 7.49 (d, 2H, ³J = 7.45 Hz, –Tol), 8.13 (d, 1H, ³J = 9.5 Hz, Ar), 8.53 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.9 Hz, Ar), 8.98 (d, 1H, ⁴J = 2.9 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.73, 20.84 (2CH₃), 21.86, 25.42 (2CH₂), 27.62 (2CH₂), 30.75, 48.04 (2CH₂), 113.10, 119.78, 121.70 (3CH), 125.97 (C), 126.14 (CH), 128.21, 129.23 (4CH, Tol), 132.14, 139.33, 142.58, 144.08, 155.90, 174.88 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3058 (w), 2917 (w), 1640 (s), 1509 (m), 1465 (s), 1329 (s), 1192 (m), 1111 (m), 1057 (m), 909 (m), 835 (m), 797 (m), 745 (m), 653 (m). MS (GC, 70 eV): m/z (%) = 378 (M⁺, 57), 377 (55), 363 (12), 349 (15), 293 (100), 287 (20), 280 (73), 247 (57), 204 (15), 177 (24), 131 (26), 57 (14), 43 (20), 41 (23), 29 (16). HRMS (ESI): calcd for C₂₃H₂₆N₂O₃: 378.1937, found: 378.1943.

1-Hexyl-6-nitro-2-p-tolylquinolin-4(1H)-one (7ae). Brown crystals, yield 55%. Mp 160–162 °C. ¹H NMR (300.13 MHz, CDCl₃ : DMSO-d₆ 6 : 1): δ = 0.76 (s, 3H, –C₅H₁₀–CH₃), 1.01–1.17 (m, 6H, –(CH₂)₂–(CH₂)₃–CH₃), 1.62 (p, ³J = 7.0 Hz, 2H, –CH₂–CH₂–C₄H₉), 2.42 (s, 3H, –CH₃, –Tol), 4.08 (t, ³J = 7.9 Hz, 2H, –CH₂–C₅H₁₁), 6.14 (s, 1H, –COCH=), 7.31 (d, ³J = 1.7 Hz, 4H, –Tol), 7.80 (d, 1H, ³J = 9.5 Hz, Ar), 8.45 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.8 Hz, Ar), 9.11 (s, 1H, ⁴J = 2.8 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.69, 20.86 (2CH₃), 21.69, 25.18, 27.66, 30.22, 48.08 (5CH₂), 113.12, 119.76, 121.70 (3CH), 125.96 (C), 126.12 (CH), 128.21, 129.25 (4CH, –Tol), 132.15, 139.36, 142.56, 144.07, 155.89, 174.87 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3077, 2918, 2855, 1640, 1508, 1466, 1240, 854, 833, 798, 745. MS (GC, 70 eV): m/z (%) = 364 (M⁺, 89), 293 (100), 280 (28), 248 (13), 247 (58), 234 (10), 204 (14), 177 (24), 131 (20), 43 (29), 41 (18), 29 (10). HRMS (ESI): calcd for C₂₂H₂₅N₂O₃: 364.1782, found: 364.1787.

6-Nitro-1-cyclohexyl-2-p-tolyl-4-quinolone (7af). Yellow crystals, yield 60%. Mp 260–262 °C. ¹H NMR (300 MHz, CDCl₃) δ = 0.9–1.29 (m, 4H, cyclohexyl), 1.81 (t, J = 12.6 Hz, 4H, cyclohexyl), 2.28 (qd, J = 12.7, 3.7 Hz, 2H, cyclohexyl), 2.39 (s, 3H, –CH₃, –Tol), 4.17 (tt, J = 12.7, 3.7 Hz, 1H, cyclohexyl), 6.17 (s, 1H, –COCH=), 7.2–7.26 (m, 4H, tolyl + CDCl₃), 7.98 (d, ³J = 9.6 Hz, 1H), 8.3 (dd, ^3,4J = 9.6, 2.9 Hz, Ar), 9.2 (d, 1H, ⁴J = 2.9 Hz, Ar). ¹³C NMR (300 MHz, CDCl₃) δ = 21.43 (CH₃), 24.98, 25.65, 26.35, 30.97, 33.96 (5CH₂), 63.93, 114.87, 120.02, 123.58, 124.84 (5CH), 127.40 (C), 127.80, 129.70 (4CH), 133.42, 140.04, 142.80, 144.60, 157.09, 176.29 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2927 (m), 2853 (m), 1607 (m), 1557 (s), 1519 (m), 1499 (m), 1446 (w), 1309 (s), 1254 (s), 1207 (m), 1182 (m), 1141 (m), 1106 (s), 1034 (m), 821 (m), 792 (m), 748 (m), 678 (m), 653 (m). MS (GC, 70 eV): m/z (%) = 362 (M⁺, 31), 281 (31), 280 (100), 234 (911), 204 (12), 190 (10), 83 (18), 55 (50), 41 (26). HRMS (EI): calcd for C₂₂H₂₂N₂O₃: 362.1624, found: 362.1630.

6-Nitro-1-pentyl-2-p-tolylquinolin-4(1H)-one (7ag). Pale yellow crystals, yield 71%. Mp 164–166 °C. ¹H NMR (250.13 MHz, DMSO-d₆): δ = 0.74 (s, 3H, –C₄H₈–CH₃), 1.07 (s, 4H, –C₂H₄–(CH₂)₂–CH₃), 1.61 (s, 2H, –CH₂–CH₂–C₃H₇), 2.44 (s, 3H, –Tol), 4.12 (s, 2H, –CH₂–C₄H₉), 6.08 (s, 1H, –COCH=), 7.41 (d, 2H, ³J = 7.2 Hz, –Tol), 7.47 (d, 2H, ³J = 7.2 Hz, –Tol), 8.09 (d, 1H, ³J = 8.4 Hz, Ar), 8.49 (d, 1H, ³J = 8.4 Hz, Ar), 8.91 (s, 1H, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.54, 20.86 (2CH₃), 21.26, 27.51, 27.72, 48.17 (4CH₂), 113.14, 119.75, 121.69 (3CH), 125.96 (C), 126.12 (CH), 128.18, 129.25 (4CH, –Tol), 132.16, 139.37, 142.56, 144.06, 155.90, 174.86 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2912 (w), 1634 (s), 1464 (s), 1329 (s), 1109 (m), 1056 (m), 911 (m), 832 (s), 745 (s), 652 (m). MS (GC, 70 eV): m/z (%) = 351 (M⁺¹, 21), 350 (M⁺, 100), 349 (M⁻¹, 14), 295 (10), 294 (19), 293 (98), 248 (10), 247 (45), 204 (14), 177 (22), 131 (21), 43 (20), 41 (11). HRMS (EI): calcd for C₂₁H₂₂N₂O₃: 350.1625, found: 350.1625.

1-n-Butyl-6-nitro-2-p-tolyl-4-quinolone (7ah). Light brown powder, yield 79%. Mp 192–194 °C. ¹H NMR (250.13 MHz, DMSO): δ = 0.69 (t, 3H, ³J = 7.0 Hz, –C₃H₆–CH₃), 1.11 (m, 2H, CH₃CH₂CH₂CH₂–), 1.6 (s, 2H, CH₃CH₂CH₂CH₂–), 2.44 (s, 3H, –CH₃, –Tol), 4.14 (s, 2H, CH₃CH₂CH₂CH₂–), 6.09 (s, 1H, –COCH=), 7.45 (dd, 4H, –Tol, ³J = 7.3 Hz), 8.1 (d, 1H, ³J = 8.5 Hz, Ar), 8.5 (d, 1H, ³J = 8.5 Hz, Ar), 8.93 (s, 1H, Ar). ¹³C NMR (75.47 MHz, DMSO): δ = 13.11, 18.92 (2CH₃), 20.86, 29.95, 47.96 (3CH₂), 113.13, 119.74, 121.67 (3CH), 125.94 (C) 126.01 (CH), 128.20, 129.25 (4CH_Ar), 132.15, 139.36, 142.52, 144.05, 155.89, 174.85 (6C). IR (ATR): [small nu, Greek, tilde] = 1638 (m), 1625 (m), 1606 (s), 1582 (m), 1508 (w), 1472 (s), 1394 (w), 1329 (s), 1251 (w), 1206 (m), 1172 (m), 1147 (w), 1135 (m), 1107 (w), 1014 (w), 975 (w), 931 (w), 911 (w), 838 (s), 825 (s), 798 (s), 767 (w), 747 (s), 730 (w), 701 (w). 672 (w), 654 (m), 628 (w), 579 (w), 537 (w). MS (GS): m/z (%) = 336 (M⁻¹, 100), 294 (19), 293 (98), 247 (44), 204 (15), 190 (10), 177 (20), 131 (20), 76 (10), 41 (13), 29 (14). HRMS (ESI): calcd for C₂₀H₂₁N₂O₃: 337.15467, found: 337.15457.

6-Nitro-1-n-propyl-2-p-tolyl-4-quinolone (7ai). Light brown powder, yield 87%. Mp 117–118 °C. ¹H NMR (250.13 MHz, DMSO): δ = 0.69 (t, 3H, Ar–CH₃, ³J = 7.1 Hz), 1.65 (d, 2H, CH₃CH₂CH₂–, ³J = 7.1 Hz), 2.45 (s, 3H, CH₃CH₂CH₂–), 4.08–4.13 (m, 2H, CH₃CH₂CH₂–), 6.11 (s, 1H, –COCH=), 7.45 (dd, 4H, –Tol, ³J = 7.6 Hz), 8.13 (d, 1H, 8-H, ³J = 8.4 Hz), 8.52 (d, 1H, 7-H, ³J = 8.4 Hz), 8.97 (d, 1H, 5-H, ⁴J = 2.0 Hz). ¹³C NMR (75.47 MHz, DMSO): δ = 10.51, 20.89 (2CH₃), 21.42, 49.69 (2CH₂), 113.11, 119.86, 121.70 (3CH), 125.97 (C), 126.10 (CH), 128.18, 129.31 (4CH), 132.23, 139.39, 142.60, 144.09, 156.03, 174.88 (C). IR (ATR): [small nu, Greek, tilde] = 2972 (w), 1626 (s), 1605 (s), 1575 (m), 1509 (m), 1470 (s), 1390 (m), 1332 (s), 1293 (s), 1222 (w), 1179 (m), 1138 (m), 1106 (m), 1056 (m), 1014 (w), 964 (w), 924 (m), 914 (w), 847 (m), 824 (s), 798 (s), 746 (s), 700 (w), 672 (w), 653 (m), 576 (w), 542 (m). MS (GS): m/z (%) = 322 (M⁻¹, 100), 294 (22), 293 (97), 248 (10), 247 (50), 204 (16), 190 (12), 177 (22), 131 (20), 76 (10), 41 (10). HRMS (ESI): calcd for C₁₉H₁₉N₂O₃: 323.13902, found: 323.13931.

1-Iso-propyl-6-nitro-2-p-tolyl-4-quinolone (7aj). Yellow powder, yield 82%. Mp 280–282 °C. ¹H NMR (250.13 MHz, CDCl₃): δ = 1.61 (s, 3H, CH₃), 1.63 (s, 3H, CH₃), 2.44 (s, 3H, Ar–CH₃), 4.69–4.84 (m, 1H, Alk-CH), 6.23 (s, 1H, –COCH=), 7.27–7.34 (m, 4H, –Tol), 7.91 (d, ³J = 9.6 Hz, 1H, 8-H), 8.37 (dd, ^3,4J = 9.6, 2.8 Hz, 1H, 7-H), 9.25 (d, ⁴J = 2.8 Hz, 1H, 5-H). ¹³C NMR (75.47 MHz, CDCl₃): δ = 21.30 (2CH₃, -Alk), 21.36 (CH₃, –Tol), 54.21 (CH, Alk), 114.55, 119.68, 123.70, 125.07 (4CH), 127.50 (2CH), 127.76 (C), 129.80 (2CH), 133.17, 140.14, 142.93, 143.76, 156.92, 176.12 (6C). IR (ATR): [small nu, Greek, tilde] = 3146 (w), 1633 (m), 1603 (s), 1506 (w), 1455 (m), 1405 (w), 1375 (w), 1332 (s), 1288 (s), 1247 (w), 1161 (m), 1136 (m), 1093 (w), 1055 (m), 1022 (w), 997 (w), 928 (w), 911 (w), 847 (s), 820 (s), 793 (m), 776 (w), 747 (s), 726 (w), 695 (w), 644 (m), 544 (w). MS (GS): m/z (%) = 322 (M⁻¹, 72), 323 (16), 281 (19), 280 (100), 252 (14), 234 (38), 206 (12), 205 (13), 204 (17), 191 (18), 190 (17), 115 (10), 43 (30), 41 (16). HRMS (ESI): calcd for C₁₉H₁₉N₂O₃: 323.1390, found: 323.1396.

6-Nitro-1-phenyl-2-p-tolyl-4-quinolone (7ak). Brown powder, yield 64%. Mp 337–338 °C. ¹H NMR (300.13 MHz, CF₃COOD, DMSO): δ = 1.95 (s, 3H, CH₃), 6.84 (dd, ³J = 8.4 Hz, 4H, Ar), 6.91–7.07 (m, 2H, Ar), 7.09–7.36 (m, 5H, Ar), 8.30 (dd, ^3,4J = 9.7 Hz, 2.5 Hz, 1H, Ar), 9.12 (d, ⁴J = 2.5 Hz, 1H, Ar). ¹³C NMR (75.47 MHz, CF₃COOD, DMSO-d₆): δ = 23.25 (–CH₃, –Tol) 113.00 (CH), 123.55 (C), 124.30, 125.56 (2CH), 131.51 (2CH), 131.85 (CH), 132.21, 132.60 (4CH), 132.79 (C), 133.70 (2CH), 134.57 (CH), 140.40, 145.77, 147.88, 149.47, 167.42, 173.74 (6C). IR (ATR): [small nu, Greek, tilde] = 3058 (w), 2334 (w), 2139 (w), 1639 (s), 1608 (s), 1508 (s), 1492 (s), 1462 (s), 1379 (s), 1332 (s), 1252 (m), 1194 (m), 1157 (w), 1146 (m), 1114 (m), 1061 (m), 1026 (m), 970 (w), 929 (w), 908 (m), 859 (s), 829 (s), 794 (s), 781 (s), 744 (s), 725 (s), 702 (s), 662 (m), 634 (m), 585 (w), 540 (s). MS (GS): m/z (%) = 356 (M⁺, 41), 328 (13), 278 (46), 277 (100), 201 (14), 199 (15), 183 (12), 119 (10), 93 (10), 77 (19), 43 (11). HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₆O₃N₂: 356.1155, found: 356.1154.

6-Nitro-2-p-tolyl-2,4,6-trimethylphenyl-4-quinolone (7al). Brown powder, yield 65%. Mp 234–236 °C. ¹H NMR (250.13 MHz, CDCl₃): δ = 1.90 (s, 6H, CH₃–Ar), 2.28 (s, 3H, o-CH₃–Ar), 2.30 (s, 3H, o-CH₃–Ar), 6.53 (s, 1H, –COCH=), 6.81 (d, ³J = 9.4 Hz, 1H, 8-H), 6.89 (s, 2H, Ar), 7.07–6.97 (m, 4H, Ar), 8.23 (dd, ^3,4J = 9.4, 2.7 Hz, 1H, 7-H), 9.34 (d, J = 2.7 Hz, 1H, 5-H). ¹³C NMR (75.47 MHz, CDCl₃): δ = 17.84 (2CH₃), 21.09, 21.27 (2CH₃), 114.46, 118.48, 123.41 (3CH), 125.72 (C), 126.47 (CH), 128.12, 128.71, 130.03 (6CH), 131.39, 133.91 (2C), 135.79 (2C), 139.78, 139.98, 143.74, 144.64, 155.34, 176.95 (6C). IR (ATR): [small nu, Greek, tilde] = 2921 (w), 1634 (s), 1608 (s), 1556 (w), 1505 (m), 1455 (w), 1372 (m), 1330 (s), 1294 (m), 1261 (m), 1245 (m), 1210 (m), 1184 (m), 1146 (w), 1129 (w), 1116 (w), 1060 (w), 1034 (w), 1017 (w), 971 (w), 938 (m), 906 (w), 852 (m), 831 (m), 817 (s), 793 (m), 747 (s), 723 (m), 671 (w), 648 (m), 632 (w), 563 (m). MS (GS): m/z (%) = 398 (M⁺, 100), 399 (27), 370 (24), 352 (11). HRMS (ESI): calcd for C₂₅H₂₂O₃N₂: 398.1625, found: 398.1625.

1-(3,5-Dimethylphenyl)-6-nitro-2-p-tolylquinolin-4(1H)-one (7am). Yellow crystals, yield 61%. Mp 303–307 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 2.27 (s, 9H, 3CH₃), 6.44 (s, 1H, –COCH=), 6.77 (s, 2H, Ar′), 6.96–7.09 (m, 1H, Ar + 1H, Ar′ + 4H, –Tol), 8.21 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.7 Hz, Ar), 9.30 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 21.08 (2CH₃, Ar′), 21.21 (CH₃, –Tol), 113.81, 119.74, 122.98 (3CH), 125.51 (C), 125.71 (CH), 127.04, 128.62, 128.86 (6CH), 131.06 (CH, –Tol), 131.96, 138.27, 139.10 (3C), 139.87 (2C), 143.37, 145.88, 155.35, 176.85 (4C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3080 (w), 2918 (w), 1640 (s), 1608 (s), 1510 (s), 1511 (m), 1462 (s), 1332 (s), 1188 (m), 1188 (m), 1118 (m), 1063 (m), 928 (m), 826 (s), 745 (s), 709 (m), 667 (m), 602 (m), 532 (s). MS (GC, 70 eV): m/z (%) = 385 (M⁺¹, 27), 384 (M⁺, 100), 356 (29), 338 (16), 295 (13). HRMS (ESI): calcd for C₂₄H₂₀N₂O₃: 384.1468, found: 384.1476.

1-(2,3-Dihydro-1H-inden-5-yl)-6-nitro-2-p-tolylquinolin-4(1H)-one (7an). Yellow crystals, yield 62%. Mp 261–263 °C. ¹H NMR (500.13 MHz CDCl₃ : DMSO-d₆ 9 : 1): δ = 1.96–2.08 (m, 2H, –CH₂CH₂CH₂–), 2.24 (s, 3H, –CH₃, –Tol), 2.74–2.90 (m, 4H, –CH₂CH₂CH₂–), 6.32 (s, 1H, –COCH=), 6.91 (d, 1H, ³J = 7.8 Hz, Ar′), 6.98–7.07 (m, 1H, Ar′ + 4H, –Tol + 1H, Ar + CDCl₃), 7.20 (d, 1H, ³J = 7.8 Hz, Ar′), 8.17 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.7 Hz, Ar), 9.15 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (500.13 MHz CDCl₃ : DMSO-d₆ 9 : 1): δ = 20.63 (CH₃), 24.75, 31.87, 32.05 (3CH₂), 112.94, 119.58, 121.90 (3CH), 124.64 (C), 124.84, 124.89, 125.08, 126.61 (4CH), 128.11 (2CH, –Tol), 128.31 (2CH, –Tol), 131.44, 135.78, 138.40, 142.62, 145.24, 145.63, 145.77, 155.16, 175.97 (9C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3044 (w), 2917 (w), 1608 (s), 1456 (s), 1333 (s), 1129 (m), 1060 (m), 911 (m), 825 (s), 745 (m), 568 (m). MS (GC, 70 eV): m/z (%) = 397 (M⁺¹, 27), 396 (M⁺, 100), 368 (24), 350 (13), 115 (13). HRMS (ESI): calcd for C₂₅H₂₀N₂O₃: 396.1468, found: 396.1474.

1-(3-Methoxyphenyl)-6-nitro-2-p-tolylquinolin-4(1H)-one (7ao). Brown crystals, yield 55%. Mp 272–274 °C. ¹H NMR (300.13 MHz CDCl₃ : DMSO-d₆ 6 : 1): δ = 2.25 (s, 3H, –CH₃, –Tol), 3.70 (s, 3H, –OCH₃), 6.32 (s, 1H, –COCH=), 6.74 (s, 1H, Ar′), 6.81 (d, 1H, ³J = 8.1 Hz, Ar′), 6.90 (dd, 1H, ³J = 8.1 Hz, ⁴J = 1.7 Hz, Ar′), 6.98–7.03 (m, 2H, –Tol), 7.09 (d, 2H, ³J = 7.9 Hz, –Tol + 1H, Ar), 7.30 (t, 1H, ³J = 8.1 Hz, Ar′), 8.23 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.6 Hz, Ar), 9.13 (d, 1H, ⁴J = 2.6 Hz, Ar). ¹³C NMR (300.13 MHz CDCl₃ : DMSO-d₆ 6 : 1): δ = 20.64 (–CH₃, –Tol), 55.02 (–OCH₃), 112.88, 114.72, 114.81, 119.47, 121.14, 121.81 (6CH), 124.80 (C), 125.31 (CH), 128.15, 128.25 (4CH, –Tol), 130.08 (CH), 131.29, 138.48, 138.70, 142.71, 145.26, 154.80, 160.03, 175.85 (8C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3055 (w), 1600 (s), 1470 (s), 1333 (s), 1177 (m), 1050 (m), 914 (w), 829 (s), 790 (s), 745 (m), 691 (s), 584 (w), 535 (m). MS (GC, 70 eV): m/z (%) = 387 (M⁺¹, 49), 386 (M⁺, 100), 385 (M⁻¹, 10), 358 (44), 356 (28), 340 (23), 312 (12). HRMS (EIHR): calcd for C₂₃H₁₈N₂O₄: 386.1261, found: 386.1261.

1-(4-Methoxyphenyl)-6-nitro-2-p-tolylquinolin-4(1H)-one (7ap). Brown crystals. 71%. Mp 252–254 °C. ¹H NMR (300.13 MHz, CDCl₃/DMSO-d₆ 8 : 1): δ = 2.01 (s, 3H, –CH₃, –Tol), 3.55 (s, 3H, –OCH₃), 6.11 (s, 1H, –COCH=), 6.78 (m, 9H, Ar), 7.95 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.8 Hz, Ar), 8.93 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (300.13 MHz, CDCl₃/DMSO-d₆ 8 : 1): δ = 20.54, 54.86 (2CH₃), 112.91 (CH), 114.38 (2CH), 119.20, 121.94 (2CH), 124.38 (C), 125.06 (CH), 128.11, 128.21, 129.88 (6CH), 130.24, 131.29, 138.38, 142.58, 145.64, 155.19, 159.14, 175.96. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2917 (w), 1633 (s), 1506 (s), 1462 (s), 1326 (s), 1246 (s), 1182 (m), 1025 (m), 825 (s), 746 (m), 532 (m). MS (GC, 70 eV): m/z (%) = 387 (M⁺¹, 55), 386 (M⁺, 100), 358 (39), 356 (23), 340 (24), 312 (11). HRMS (EIHR): calcd for C₂₃H₁₈N₂O₄: 386.1261, found: 386.1263.

6-Nitro-1-(3-bromphenyl)-2-p-tolyl-4-quinolone (7aq). Pale brown crystals, yield 48%. Mp 320–322 °C. ¹H NMR (300.13 MHz, CDCl₃/DMSO (8 : 1)) δ = 1.86 (s, 3H, CH₃), 5.95 (s, 1H, Ar), 6.62–6.65 (m, 5H, Ar), 6.81 (d, ³J = 7.0 Hz, 1H, Ar), 6.91 (t, ³J = 7.9 Hz, 1H, Ar), 7.02 (s, 1H, Ar), 7.12 (d, ³J = 7.6 Hz, 1H, Ar), 7.86 (dd, ³J = 9.3 Hz, ⁴J = 2.7 Hz, 1H, Ar), 8.75 (d, ⁴J = 2.7 Hz, 1H, Ar). ¹³C NMR (75 MHz, CDCl₃) δ = 20.19 (CH₃), 112.59, 118.64, 121.54 (3CH), 122.02, 124.42 (2C), 125.11, 127.62 (2CH), 127.83, 127.86 (4CH), 130.30 (CH), 130.39 (C), 131.66, 131.81 (2CH), 138.32, 138.51, 142.40, 144.61, 154.11, 175.41 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3075 (w), 1644 (m), 1609 (m), 1586 (m), 1506 (m), 1471 (s), 1377 (m), 1334 (s), 1191 (w), 1060 (w), 909 (w), 859 (M), 828 (s), 794 (s), 745 (m), 702 (m), 656 (m), 533 (m). MS (GC, 70 eV): m/z (%) = 437 (M⁺¹, 28), 436 (M⁺, C₂₂H₁₅N₂O₃⁸⁰Br, 99), 435 (M⁺¹, 34), 434 (M⁺, C₂₂H₁₅N₂O₃⁸¹Br, 100), 408 (26), 390 (12), 388 (15), 281 (12), 280 (26), 278 (13), 266 (10), 265 (14), 164 (14), 139 (15), 115 (16), 75 (12). HRMS (EI): calcd for C₂₂H₁₅N₂O₃⁸⁰Br: 434.0261, found: 434.0265; calcd for C₂₂H₁₅N₂O₃⁸¹Br: 436.0240, found: 436.0246.

1-(3,4-Dimethoxyphenethyl)-6-nitro-2-phenylquinolin-4(1H)-one (7ba). Dark gray crystals, yield 89%. Mp 156–158 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 2.84 (t, 2H, ³J = 7.1 Hz, –CH₂CH₂Ar), 3.60 (s, 3H, –OCH₃), 3.72 (s, 3H, –OCH^′₃), 4.34 (br s, 2H, –CH₂CH₂Ar), 6.09 (s, 1H, –COCH=), 6.25–6.40 (m, 2H, Ar′), 6.77 (d, 1H, ³J = 8.1 Hz, Ar′), 7.34–7.64 (m, 5H, Ph), 8.28 (d, 1H, ³J = 9.4 Hz, Ar), 8.56 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.7 Hz, Ar), 8.99 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 33.40, 49.87 (2-CH₂–), 55.24, 55.52 (2-OCH₃), 111.83, 112.16, 113.01, 119.99, 120.56, 121.68 (6CH, Ar), 125.96 (C), 126.18 (CH), 128.28, 128.59 (4CH, Ph), 129.29 (C), 129.62 (CH, Ph), 134.85, 142.64, 144.03, 147.64, 148.63, 155.83, 174.92 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2936 (w), 1634 (s), 1609 (m), 1515 (s), 1471 (s), 1421 (w), 1392 (w), 1332 (s), 1296 (m), 1264 (s), 1237 (s), 1189 (m), 1171 (m), 1144 (s), 1112 (m), 1065 (w), 1030 (m), 934 (w), 910 (w), 840 (m), 806 (s), 762 (m), 745 (s), 703 (m), 675 (m), 626 (w), 542 (w). MS (GC, 70 eV): m/z (%) = 430 (M⁺, 15), 413 (48), 400 (33), 277 (57), 249 (45), 233 (20), 206 (12), 199 (18), 183 (16), 178 (32), 1643 (89), 151 (86), 141 (21), 131 (11), 78 (40), 65 (26), 63 (100), 57 (15), 44 (57). HRMS (ESI): calcd for C₂₅H₂₂N₂O₃: 430.1523, found: 430.1529.

1-(4-Methoxybenzyl)-6-nitro-2-phenylquinolin-4(1H)-one (7bb). Brown crystals, yield 61%. Mp 227–229 °C. ¹H NMR (300.13 MHz; DMSO-d₆): δ = 3.67 (s, 3H, –OCH₃), 5.33 (s, 2H, –CH₂–), 6.20 (s, 1H, –COCH=), 6.83 (d, 2H, ³J = 8.5 Hz, Ar′), 6.98 (d, 2H, ³J = 8.5 Hz, Ar′), 7.50 (s, 5H, –Ph), 7.80 (d, 1H, ³J = 9.5 Hz, Ar), 8.37 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.7 Hz, Ar), 8.92 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 51.229 (CH₂), 54.96 (CH₃), 113.27 (CH), 114.22 (2CH), 120.34, 121.53 (2CH), 126.11 (C), 126.13 (CH), 126.94 (2CH), 127.50 (C), 128.10, 128.74 (4CH), 129.90 (CH), 134.69, 142.75, 144.36, 156.09, 158.49, 175.12 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2952 (w), 1608 (s), 1512 (s), 1470 (m), 1332 (s), 1245 (s), 1172 (m), 1028 (s), 802 (s), 709 (s). MS (GC, 70 eV): m/z (%) = 386 (M⁺, 4), 122 (38), 121 (100), 78 (12), 77 (14). HRMS (ESI): calcd for C₂₃H₁₈N₂O₄: 386.1260, found: 386.1267.

6-Nitro-1-phenethyl-2-phenylquinolin-4(1H)-one (7bc). Yellow crystals, yield 79%. Mp 263–265 °C. ¹H NMR (300.13 MHz DMSO-d₆/CF₃COOD): δ = 2.90 (s, 2H, –CH₂CH₂Ph), 4.75 (s, 2H, –CH₂CH₂Ph), 6.47 (d, 2H, ³J = 6.5 Hz, Ph′), 6.87–7.15 (m, 3H, Ph′ + 3H, Ph), 7.27–7.49 (m, 2H, Ph + 1H, –COCH=), 8.28 (d, 1H, ³J = 9.2 Hz, Ar), 8.67 (d, 1H, ³J = 9.2 Hz, Ar), 9.20 (s, 1H, Ar). ¹³C NMR (300.13 MHz DMSO-d₆/CF₃COOD): δ = 37.10, 55.30 (2CH₂), 112.65, 123.44, 124.22 (3CH), 124.28 (C), 129.91 (CH), 130.33, 131.07 (4CH), 131.15 (CH), 131.44, 131.67 (4CH), 133.72 (CH), 135.60, 138.28, 145.07, 148.22, 165.60, 173.50 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3055 (s), 1634 (w), 1600 (m), 1557 (s), 1519 (m), 1494 (m), 1468 (w), 1443 (m), 1391 (s), 1368 (s), 1329 (w), 1294.3 (m), 1255 (m), 1192 (m), 1166 (m), 1145 (m), 1114 (m), 1078 (m), 1030 (s), 984 (m), 924 (m), 857 (w), 822 (w), 800 (m), 761 (w), 734 (w), 706 (w), 671 (m), 631 (m), 591 (m), 545 (m). MS (GC, 70 eV): m/z (%) = 370 (M⁺, 43), 279 (100), 233 (54), 177 (17), 131 (21). HRMS (EI): calcd for C₂₃H₁₈N₂O₃: 370.1312, found: 370.1312.

6-Nitro-4-oxo-2-phenyl-1-(3-phenylpropyl)quinoline (7bd). Yellow crystals, yield 66%. Mp 180 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 1.94 (br s, 2H, –CH₂CH₂CH₂Ph), 2.47 (m, 2H, –CH₂CH₂CH₂Ph), 4.10 (br s, 2H, –CH₂CH₂CH₂Ph), 6.09 (s, 1H, –COCH=), 6.90–7.30 (m, 5H, Ph′), 7.56 (s, 5H, Ph), 8.05 (d, 1H, ³J = 8.6 Hz, Ar), 8.47 (d, 1H, ³J = 8.6 Hz, Ar), 8.93 (s, 1H, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 29.09, 31.60, 47.92 (3C, –n-C₃H₆Ph), 113.08, 119.58, 121.71, 125.88 (4CH, Ar), 125.95 (1C, Ph), 126.01 (1C, Ar), 127.90, 128.26 (4CH, Ph), 128.11, 128.73 (4CH, Ph′), 129.69 (1CH, Ph′), 134.77, 140.09, 142.56, 144.07, 155.67, 174.91 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3055 (w), 2939 (w), 1627 (s), 1609 (s), 1580 (m), 1556 (w), 1516 (w), 1494 (w), 1465 (m), 1389 (m), 1331 (s), 1296 (m), 1211 (w), 1188 (m), 1167 (m), 1144 (m), 1113 (m), 1069 (m), 1050 (m), 1031 (w), 1013 (w), 933 (w), 910 (w), 846 (m), 814 (w), 763 (m), 746 (m), 735 (s), 704 (m), 692 (s), 674 (s). MS (GC, 70 eV): m/z (%) = 384 (M⁺, 100), 354 (11), 280 (18), 279 (92), 266 (20), 233 (45), 177 (20), 131 (15), 118 (15), 91 (81). HRMS (ESI): calcd for C₂₄H₂₂N₂O₃: 385.1547, found: 385.1547.

1-Heptyl-6-nitro-2-phenylquinolin-4(1H)-one (7be). Dark crystals, yield 90%. Mp 142–144 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.81 (t, 3H, ³J = 6.7 Hz, –C₆H₁₂–CH₃), 0.98–1.20 (br m, 8H, –C₂H₄–C₄H₈–CH₃), 1.61 (br s, 2H, –CH₂–CH₂–C₅H₁₁), 4.11 (t, 2H, ³J = 7.4 Hz, –CH₂–C₆H₁₃), 6.12 (s, 1H, –COCH=), 7.61 (s, 5H, Ph), 8.11 (d, 1H, ³J = 9.5 Hz, Ar), 8.51 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.5 Hz, Ar), 8.94 (d, 1H, ⁴J = 2.5 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.77 (–C₆H₁₂–CH₃), 21.84, 25.46, 27.63, 27.70, 30.79, 48.15 (6CH₂, –C₆H₁₂–CH₃), 113.07, 119.72, 121.69 (3CH), 125.95 (C), 126.14 (CH), 128.27 (2CH, Ph), 128.73 (2CH, Ph), 129.70 (CH, Ph), 134.94, 142.57, 144.03, 155.69, 174.88 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3062 (w), 2924 (w), 2853 (w), 1640 (m), 1602 (m), 1583 (m), 1515 (m), 1468 (s), 1393 (w), 1328 (s), 1188 (w), 1170 (w), 1140 (w), 1110 (m) 1057 (w), 1014 (w), 935 (w), 910 (w), 852 (m), 823 (m), 802 (m), 765 (s), 745 (s), 705 (s), 674 (m), 633 (w). MS (GC, 70 eV): m/z (%) = 364 (M⁺, 70), 293 (14), 287 (19), 279 (100), 266 (75), 245 (18), 233 (62), 204 (10), 191 (12), 177 (29), 131 (21), 57 (10), 43 (11), 41 (12). HRMS (EI): calcd for C₂₂H₂₄N₂O₃: 364.1781, found: 364.1773.

1-Cyclohexane-6-nitro-4-oxo-2-phenylquinoline (7bf). Yellow crystals, yield 60%. Mp 272–274 °C. ¹H NMR (300.13 MHz DMSO-d₆/CF₃COOD): δ = 0.80–2.50 (m, 10H, cyclohexyl), 4.55 (t, 1H, ³J = 11.6 Hz, cyclohexyl), 6.95 (s, 1H, –COCH=), 7.40–7.70 (m, 5H, Ph), 8.62 (s, 2H, Ar), 9.20 (s, 1H, Ar). ¹³C NMR (250.13 MHz DMSO-d₆/CF₃COOD): δ = 25.86 (1-CH₂–), 27.80, 32.17 (4-CH₂–), 69.15, 112.96, 123.54, 124.18 (4CH), 125.46 (1C), 128.67 (1CH), 128.94, 131.12 (4CH), 132.72 (1CH), 136.80, 144.92, 146.51, 163.94, 174.20 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2938 (s), 2854 (s), 1645 (m), 1610 (s), 1581 (s), 1513 (s), 1469 (m), 1442 (m), 1383 (s), 1330 (w), 1278 (s), 1262 (s), 1225 (s), 1188 (s), 1167 (s), 1141 (s), 1099 (s), 1067 (s), 1031 (s), 984 (s), 934 (s), 913 (s), 857 (m), 829 (s), 793 (s), 767 (m), 744 (m), 706 (w), 677 (s), 636 (s), 573 (s), 543 (s). MS (GC, 70 eV): m/z (%) = 348 (M⁺, 24), 266 (100), 190 (11), 83 (14), 55 (27), 41 (11). HRMS (EI): calcd for C₂₁H₂₀N₂O₃: 348.1467, found: 348.1468.

1-Hexyl-6-nitro-2-phenylquinolin-4(1H)-one (7bg). Red-Brown crystals, yield 81%. Mp 159–160 °C. ¹H NMR (300.13 MHz; DMSO-d₆): δ = 0.77 (t, 3H, ³J = 7.0 Hz, –CH₃), 0.97–1.16 (br m, 6H, –(CH₂)₂–(CH₂)₃–CH₃), 1.53–1.64 (m, 2H, –CH₂–CH₂–C₄H₉), 4.11 (t, 2H, ³J = 7.9 Hz, –CH₂–C₅H₁₁), 6.12 (s, 1H, –COCH=), 7.62 (s, 5H, Ph), 1.05 (d, 1H, ³J = 9.5 Hz, Ar), 8.51 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.9 Hz, Ar), 8.94 (d, 1H, ⁴J = 2.9 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.68 (–CH₃), 21.70, 25.19, 27.69, 30.19, 48.19 (5CH₂), 113.08, 119.76, 121.72 (3CH), 125.96 (C), 126.19 (CH), 128.30, 128.77 (4CH, Ph), 129.73 (CH, Ph), 134.96, 142.60, 144.05, 155.74, 174.92 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2922 (w), 1641 (m), 1602 (m), 1583 (m), 1515 (w), 1469 (s), 1394 (w), 1328 (s), 1249 (w), 1188 (w), 1172 (m), 1111 (m), 1056 (m), 1019 (w), 991 (w), 935 (w), 911 (w), 853 (m), 823 (w), 801 (w), 766 (s), 745 (s), 707 (s), 674 (m), 633 (w), 539 (w). MS (GC, 70 eV): m/z (%) = 350 (M⁺, 95), 279 (100), 273 (12), 266 (25), 233 (69), 221 (12), 204 (15), 190 (14), 177 (17), 165 (11), 131 (25), 76 (10), 43 (30), 41 (24). HRMS (ESI): calcd for C₂₁H₂₂N₂O₃: 350.1624, found: 350.1630.

1-(3,5-Dimethoxybenzen)-6-nitro-4-oxo-2-phenylquinoline (7bh). Yellow crystals, yield 47%. Mp 248–251 °C. ¹H NMR (300.13 MHz DMSO-d₆/CDCl₃ 1 : 5): δ = 3.38 (s, 6H, 2CH₃O-), 6.05 (d, 3H, ⁴J = 2.5 Hz, Ar), 6.10 (s, 1H, –COCH=), 6.88 (d, 1H, ³J = 9.4 Hz, Ar), 6.95 (s, 5H, Ph), 7.93 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.6 Hz, Ar), 8.85 (d, 1H, ⁴J = 2.6 Hz, Ar). ¹³C NMR (300.13 MHz DMSO-d₆/CDCl₃ 1 : 5): δ = 55.07 (2CH₃), 100.73 (1CH), 107.41 (2CH), 112.91, 119.41, 121.91 (3CH), 124.77 (1C), 125.29 (1CH), 127.46, 128.16 (4CH), 128.64 (1CH), 134.06, 138.98, 142.73, 145.01, 154.40 (5C), 160.91 (2C), 175.93 (1C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3078 (w), 2937 (w), 1583 (s), 1456 (s), 1330 (s), 1193 (m), 1155 (s), 1058 (m), 922 (w), 820 (m), 745 (m), 698 (m), 588 (m). MS (GC, 70 eV): m/z (%) = 403 (M⁺¹, 29), 402 (M⁺, 100), 356 (14). HRMS (EI): calcd for C₂₃H₁₈N₂O₅: 402.1210, found: 402.1212.

6-Nitro-1-(3,4-dimethoxyphenethyl)-2-p-tolyl-4-quinolone (7ca). Yellow crystals, yield 82%. ¹H NMR (300 MHz, CDCl₃) δ = 0.93 (t, ³J = 7.3 Hz, 3H, –CH₂CH₂CH₂CH₃), 1.32–1.45 (m, 2H, –CH₂CH₂CH₂CH₃), 1.53–1.63 (m, 2H, –CH₂CH₂CH₂CH₃), 2.43 (t, 2H, ³J = 7.1 Hz, –CH₂CH₂CH₂CH₃), 3.04 (t, ³J = 7.1 Hz, 2H, –NCH₂CH₂–), 3.79 (s, 3H, –OCH₃), 3.84 (s, 3H, –OCH₃), 4.41 (t, ³J = 7.2 Hz, 2H, –NCH₂CH₂–), 6.20 (s, 1H, Ar), 6.52 (d, ⁴J = 1.9 Hz, 1H, Ar), 6.62 (dd, ³J = 8.1 Hz, ⁴J = 1.9 Hz, 1H, Ar), 6.79 (d, ³J = 8.2 Hz, 1H, Ar), 7.65 (d, ⁴J = 9.5 Hz, 1H, Ar), 8.40 (dd, ³J = 9.5 Hz, ⁴J = 2.8 Hz, 1H, Ar), 9.22 (d, ⁴J = 2.8 Hz, 1H, Ar). ¹³C NMR (63.00 MHz, CDCl₃) δ = 13.66 (CH₃), 22.36, 30.51, 33.47, 34.45, 47.87 (5CH₂), 55.96 (2CH₃), 111.70, 111.77, 112.43, 117.04, 120.73, 123.55, 126.09 (7CH), 126.45, 128.89, 142.96, 144.18, 148.48, 149.34, 156.12, 176.50 (8C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2955 (w), 2935 (w), 1632 (s), 1606 (m), 1576 (m), 1515 (s), 1466 (s), 1446 (m), 1421 (m), 1399 (w), 1334 (s), 1283 (m), 1265 (s), 1237 (s), 1213 (m), 1189 (w), 1159 (s), 1142 (s), 1101 (m), 1023 (m), 939 (w), 930 (m), 912 (w), 840 (s), 821 (s), 804 (m), 761 (m), 744 (s), 671 (w), 648 (m), 625 (m), 560 (w), 542 (w). MS (GC, 70 eV): m/z (%) = 410 (M⁺, 5), 409 (M⁺, 5), 151 (100). HRMS (ESI): calcd for C₂₃H₂₆N₂O₅: 410.1828, found: 410.1836.

2-Butyl-1-(3,5-dimethoxyphenyl)-6-nitroquinolin-4(1H)-one (7cb). Brown crystals, yield 39%. Mp 162–164 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.79 (t, 3H, ³J = 7.1 Hz, –C₃H₆–CH₃), 1.18–1.29 (m, 2H, –C₂H₄–CH₂–CH₃), 1.48–1.59 (m, 2H, –CH₂–CH₂–C₂H₅), 2.40 (t, 2H, ³J = 7.5 Hz, –CH₂–C₃H₇), 3.85 (s, 6H, 2-OCH₃), 6.28 (s, 1H, –COCH=), 6.83 (s, 3H, Ar′), 7.00 (d, 1H, ³J = 9.3 Hz, Ar), 8.31 (d, 1H, ³J = 9.3 Hz, Ar), 8.85 (s, 1H, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 13.40 (–CH₃), 21.65, 30.03, 32.46 (3CH₂–), 55.79 (2OCH₃), 101.92 (CH), 107.20 (2CH, Ar′), 110.26, 120.09, 121.10, 124.28 (4CH), 125.78, 139.13, 142.47, 145.68, 156.39 (5C), 161.72 (2C, Ar′), 175.51 (C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2959 (w), 1632 (m), 1607 (s), 1584 (s), 1515 (w), 1467 (s), 1326 (s), 1297 (m), 1256 (m), 1195 (s), 1156 (s), 1060 (s), 992 (w), 930 (w), 910 (w), 860 (w), 844 (m), 814 (m), 746 (m), 710 (m), 670 (w), 618 (w), 591 (m), 536 (m). MS (GC, 70 eV): m/z (%) = 382 (M⁺, 39), 340 (100), 325 (10), 323 (18), 311 (71), 297 (11), 283 (10), 265 (10). HRMS (ESI): calcd for C₂₁H₂₂N₂O₅: 382.1518, found: 382.1529.

2-Butyl-1-(4-methoxyphenyl)-6-nitroquinolin-4(1H)-one (7cc). Brown crystals, yield 72%. Mp 171–173 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.76 (t, 3H, ³J = 7.3 Hz, –CH₃), 1.14–1.27 (m, 2H, –CH₂CH₃), 1.48 (m, 2H, –CH₂CH₂CH₃), 2.34 (t, 2H, ³J = 8.1 Hz, =NCH₂–), 3.92 (s, 3H, –OCH₃), 6.31 (s, 1H, –COCH=), 6.89 (d, 1H, ³J = 9.4 Hz, Ar), 7.26 (d, 2H, ³J = 8.9 Hz, Ar), 7.52 (d, 2H, ³J = 8.9 Hz, Ar), 8.30 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.8, Ar), 8.88 (d, 1H, ⁴J = 2.8, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.32 (CH₃), 21.59, 29.79, 32.84 (CH₂), 55.57 (CH₃), 110.46 (CH), 115.57 (2CH), 119.93, 121.22 (2CH), 124.47 (C), 125.72 (CH), 129.98 (C), 130.27 (2CH), 142.46, 146.35, 156.97, 159.97, 175.52 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2930 (w), 1610 (s), 1506 (s), 1464 (s), 1330 (s), 1244 (s), 1031 (m), 918 (m), 823 (m), 745 (m), 549 (m). MS (GC, 70 eV): m/z (%) = 352 (M⁺, 22), 311 (18), 310 (100), 309 (23), 121 (33). HRMS (EI): calcd for C₂₀H₂₀N₂O₄: 352.1418, found: 352.1419.

2-Butyl-1-(4-tert-butylphenyl)-6-nitroquinolin-4(1H)-one (7cd). Brown crystals, yield 42%. Mp 127–129 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.67 (t, 3H, ³J = 7.3 Hz, –CH₃), 0.83–1.30 (br m, 6H), 1.41 (s, 9H, 3CH₃), 2.31 (t, 2H, ³J = 8.0 Hz, –CH₂), 6.34 (s, 1H, COCH=), 6.86 (d, 1H, ³J = 9.4 Hz, Ar), 7.50 (d, 2H, ³J = 8.5 Hz, Ph), 7.75 (d, 2H, ³J = 8.5 Hz, Ph), 8.33 (dd, 1H, ³J = 9.4 Hz, ⁴J = 2.8 Hz, Ar), 8.91 (d, 1H, ⁴J = 2.4 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO): δ = 13.01 (1CH₃), 21.45, 29.82 (2CH₂), 30.97 (3CH₃), 32.67 (CH₂), 34.67 (C), 110.61, 119.80, 121.27 (3CH), 124.46 (C), 125.83 (CH), 127.25, 128.60 (4CH), 134.85, 142.51, 145.98, 152.80, 156.67, 175.49. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2958 (m), 1633 (m), 1610 (m), 1520 (m), 1464 (m), 1335 (s), 1107 (m), 919 (w), 837 (m), 745 (m), 569 (m). MS (GC, 70 eV): m/z (%) = 378 (M⁺, 15), 337 (13), 336 (66), 322 (21), 321 (100), 275 (10). HRMS (EI): calcd for C₂₃H₂₆N₂O₃: 378.1938, found: 378.1938.

6-Nitro-(3,4-dimethoxyphenethyl)-2-pentyl-4-quinolone (7da). Yellow crystals, yield 60%. Mp 170–172 °C. ¹H NMR (300 MHz, CDCl₃) δ = 0.89 (t, ³J = 9.3, 3H, –(CH₂)₄CH₃), 1.31–1.36 (m, 4H, –(CH₂)₄CH₃), 1.58–1.63 (m, 2H, –(CH₂)₄CH₃), 2.42 (t, ³J = 7.2 Hz, 2H, –(CH₂)₄CH₃), 3.04 (t, ³J = 7.2 Hz, 2H, –NCH₂CH₂–), 3.79 (s, 3H, –OCH₃), 3.85 (s, 3H, –OCH₃), 4.41 (t, ³J = 7.2 Hz, 2H, –NCH₂CH₂–), 6.21 (s, 1H, Ar), 6.52 (d, ⁴J = 2.0 Hz, 1H, Ar), 6.62 (dd, ³J = 8.1 Hz, ⁴J = 2.0 Hz, 1H, Ar), 6.79 (d, J = 8.2 Hz, 1H, Ar), 7.65 (d, ³J = 9.5 Hz, 1H, Ar), 8.41 (dd, ³J = 9.5 Hz, ⁴J = 2.8 Hz, 1H, Ar), 9.18 (d, ⁴J = 2.8 Hz, 1H, Ar). ¹³C NMR (300 MHz, CDCl₃) δ = 13.85 (CH₃), 22.26, 28.14, 31.36, 33.73, 34.46, 47.86 (6CH₂), 55.95 (2CH₃), 111.68, 111.76, 112.44, 117.01, 120.72, 123.59, 126.10 (7CH), 126.47, 128.86, 142.98, 144.17, 148.50, 149.35, 156.11, 176.52 (8C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2953 (w), 1633 (s), 1608 (m), 1575 (m), 1516 (s), 1464 (m), 1414 (w), 1332 (s), 1298 (w), 1284 (w), 1264 (m), 1237 (s), 1208 (w), 1158 (s), 1142 (m), 1099 (s), 1026 (m), 932 (w), 912 (w), 845 (w), 832 (m), 821 (w), 802 (2), 765 (w), 744 (m), 673 (w), 650 (w), 627 (w), 601 (w), 561 (w), 542 (w). MS (GC, 70 eV): m/z (%) = 424 (M⁻¹, 3), 407 (23), 152 (11), 151 (100). HRMS (EI): calcd for C₂₄H₂₉N₂O₅: 425.2071, found: 425.2071.

1-(4-Methoxybenzyl)-6-nitro-2-pentylquinolin-4(1H)-one (7db). Pale pink crystals, yield 51%. Mp 120–122 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 0.87 (t, 3H, ³J = 7.1 Hz, –C₄H₈–CH₃), 1.30–1.40 (m, 4H, –C₂H₄–C₂H₄–CH₃), 1.70 (p, 2H, ³J = 7.5 Hz, –CH₂–CH₂–C₃H₇), 2.68 (t, 2H, ³J = 7.8 Hz, –CH₂–C₄H₉), 3.77 (s, 3H, –OCH₃), 5.39 (s, 2H, –CH₂–), 6.34 (s, 1H, –COCH–), 6.86 (d, 2H, ³J = 8.8 Hz, Ar′), 6.95 (d, 2H, ³J = 8.8 Hz, Ar′), 7.40 (d, 1H, ³J = 9.5 Hz, Ar), 8.23 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.8 Hz, Ar), 9.21 (d, 1H, ⁴J = 2.8 Hz, Ar). ¹³C NMR (300 MHz, CDCl₃): δ = 13.77 (CH₃), 22.23, 28.21, 31.22, 33.78, 49.76 (5CH₂), 55.29 (CH₃), 112.44 (CH), 114.86 (2CH), 117.88, 123.13 (2CH), 126.04 (2CH), 126.17, 126.28 (2C), 126.32 (2CH), 143.05, 144.87, 156.18, 159.48, 176.77. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2931 (w), 1632 (s), 1609 (s), 1514 (m), 1471 (s), 1334 (s), 1289 (s), 1248 (s), 1176 (s), 1099 (m), 1034 (m), 831 (m), 800 (m), 743 (s), 668 (m), 553 (m). MS (GC, 70 eV): m/z (%) = 380 (M⁺, 3), 121 (100). HRMS (ESI-TOF): calcd for C₂₂H₂₄N₂O₄: 380.1731, found: 380.1734.

General procedure for the synthesis of 8

A predried Schlenk flask was charged with a magnetic stirrer, 4-quinolone 7 (200 mg, 1 equiv.), 10% Pd/C (0.1 wt equiv.) and a fresh distilled methanol (20 mL). The Schlenk tube was threefold refilled with hydrogen. After 4–5 h in an atmosphere of hydrogen and an intense stirring at room temperature (TLC control) the reaction mixture was filtered through a fine silica gel pad and purified by a column chromatography (silica gel, methanol/ethyl acetate, 1 : 80) or recrystallized from a solution of ethyl acetate and n-heptane.

6-Amino-1-(3,4-dimethoxyphenethyl)-2-p-tolylquinolin-4(1H)-one (8aa). Yellow crystals, yield 64%. Mp 219–221 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 2.41 (s, 3H, –Tol), 2.82 (t, 2H, ³J = 9.4 Hz, =N–CH₂–CH₂–), 3.59 (s, 3H, Ar′ + H₂O), 3.73 (s, 3H, Ar′), 4.21 (t, 2H, ³J = 9.4 Hz, =N–CH₂–CH₂–), 5.40 (br s, 2H, –NH₂), 5.74 (s, 1H, –COCH=), 6.24 (d, 1H, ⁴J = 1.8 Hz, Ar), 6.40 (dd, 1H, ⁴J = 1.8 Hz, ³J = 8.1 Hz, Ar), 6.78 (d, 1H, ³J = 8.1 Hz, Ar), 7.15–7.21 (m, 2H, –Tol + 1H, Ar′), 7.32 (d, 2H, ³J = 7.9 Hz, –Tol), 7.42 (d, 2H, ³J = 2.8 Hz, Ar′), 7.79 (d, 1H, ³J = 9.2 Hz, Ar′). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 21.20 (CH₃), 34.49, 49.34 (2CH₂), 55.52, 55.89 (2CH₃), 109.37, 111.21, 111.30, 111.52, 117.59, 120.61, 121.57 (7CH), 128.31 (2CH), 128.61 (C), 129.02 (2CH), 129.49, 133.18, 133.47, 138.99, 143.09, 147.93, 148.93, 153.59, 176.52 (9C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3314 (w), 2915 (w), 1589 (s), 1564.9 (s), 1511 (s), 1485 (s), 1418 (m), 1311 (m), 1253 (s), 1236 (s), 1177 (m), 1153 (s), 1030 (s), 942 (w), 834 (s), 806 (s), 757 (m), 624 (m), 556 (m). MS (GC, 70 eV): m/z (%) = 415 (M⁺¹, 18), 414 (M⁺, 75), 413 (M⁻¹, 11), 264 (30), 263 (100), 262 (10), 249 (10), 248 (65), 165 (11), 147 (15). HRMS (EI): calcd for C₂₆H₂₆N₂O₃: 414.1938, found: 414.1930.

6-Amino-1-(4-methoxybenzyl)-2-p-tolylquinolin-4(1H)-one (8ab). Yellow crystals, yield 89%. Mp 267–269 °C. ¹H NMR (250 MHz, DMSO-d₆): δ = 2.36 (s, 3H, –CH₃, –Tol), 3.71 (s, 3H, –OCH₃, –Ar′), 5.25 (s, 2H, –CH₂–), 5.39 (s, 2H, –NH₂), 5.89 (s, 1H, –COCH=), 6.83–6.98 (m, 5H, Ar), 7.25–7.40 (m, 6H, Ar). ¹³C NMR (300 MHz, DMSO-d₆): δ = 21.24 (CH₃), 51.68 (CH₂), 55.21 (CH₃), 108.92, 111.43 (2CH), 114.29 (2CH), 118.78, 121.54 (2CH), 126.62, 128.06 (4CH), 128.36, 128.53 (2C), 129.20 (2CH), 132.91, 134.21, 139.52, 143.06, 154.06, 158.83, 176.75 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3213 (w), 1557 (s), 1486 (s), 1417 (m), 1300 (m), 1248 (s), 1180 (s), 1023 (m), 811 (s), 560 (m). MS (GC, 70 eV): m/z (%) = 370 (M⁺, 22), 250 (15), 122 (10), 121 (100). HRMS (EI-HR): calcd for C₂₄H₂₂N₂O₂: 370.1676, found: 370.1672.

6-Amino-1-(1-phenylethyl)-2-p-tolylquinolin-4(1H)-one (8ac). Yellow crystals, yield 62%. Mp 153–155 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 1.93 (t, 3H, ³J = 6.5 Hz, PhCH₃CH), 2.36 (s, 3H, –CH₃, –Tol), 3.15–5.50 (–NH₂ + H₂O), 5.62 (q, 1H, ³J = 6.8 Hz, PhCH₃CH), 5.79 (solvent CH₂Cl₂), 5.88 (s, 1H, –COCH=), 6.75 (dd, 1H, ³J = 9.2 Hz, ⁴J = 2.8 Hz, Ar), 6.98 (d, 1H, ³J = 9.2 Hz, Ar), 7.24 (d, 2H, ³J = 7.8 Hz, Ar), 7.29–7.37 (m, 5H, Ar), 7.41 (d, 1H, ⁴J = 2.8 Hz, Ar), 7.48 (d, 2H, ³J = 7.8 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 17.32, 20.73 (2CH₃), 57.75 (CH, –CHCH₃Ph), 106.34, 109.84, 119.58, 120.82 (4CH), 125.22 (2CH), 126.95, 127.40, 127.51 (3CH), 127.59 (C), 128.77, 129.37 (4CH), 130.20, 133.82, 138.82, 140.46, 144.72, 153.30, 174.95 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3222 (w), 2919 (m), 1588 (s), 1563 (s), 1487 (s), 1415 (m), 1377 (m), 1282 (m), 1258 (s), 1179 (m), 1075 (m), 1018 (m), 814 (s), 558 (m). MS (GC, 70 eV): m/z (%) = 355 (M⁺¹, 6), 349 (50), 348 (100), 347 (11), 264 (22), 263 (92), 251 (10), 250 (53), 249 (19), 248 (50), 147 (11). HRMS (EIHR): calcd for C₂₄H₂₂N₂O: 354.4401, found: 354.4398.

6-Amino-1-heptyl-2-p-tolylquinolin-4(1H)-one (8ad). Yellow crystals, yield 77%. Mp 177–178 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.81 (t, 3H, ³J = 6.9 Hz, C₆H₁₂–CH₃), 0.90–1.25 (br m, 8H, CH₂–(CH₂)₄–CH₃), 1.56 (br s, 2H, –CH₂–CH₂–C₅H₁₁), 2.41 (s, 3H, Tol–CH₃), 4.00 (t, 2H, ³J = 7.1 Hz, –CH₂–C₆H₁₃), 5.43 (s, 2H, NH₂), 5.77 (s, 1H, –COCH=), 7.14 (dd, 1H, ³J = 9.0 Hz, ⁴J = 2.2 Hz, Ar), 7.36 (s, 4H, –Tol), 7.40 (d, 1H, ⁴J = 2.2 Hz, Ar), 7.58 (d, 1H, ³J = 9.0 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 13.74, 20.80 (2CH₃), 21.89, 25.54, 27.72, 28.09, 30.81, 47.10 (6CH₂), 106.28, 109.57, 118.26, 120.88 (4CH), 128.24 (2CH, –Tol), 128.39 (C), 129.06 (2CH, –Tol), 131.89, 133.36, 138.52, 145.12, 152.33, 174.84 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3382 (w), 3224 (m), 2918 (m), 1644 (w), 1588 (s), 1562 (s), 1493 (s), 1415 (m), 1379 (m), 1282 (m), 1179 (m), 1107 (w), 937 (w), 822 (s), 717 (m), 558 (m). MS (GC, 70 eV): m/z (%) = 349 (M⁺¹, 25), 348 (M⁺, 100), 263 (64), 250 (31), 248 (33), 221 (12), 147 (10), 41 (11). HRMS (ESI): calcd for C₂₃H₂₈N₂O: 348.2196, found: 348.2202.

6-Amino-1-hexyl-2-p-tolylquinolin-4(1H)-one (8ae). Yellow crystals, yield 82%. Mp 196–197 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.77 (t, 3H, ³J = 7.0 Hz, –C₅H₁₀–CH₃), 0.97–1.15 (m, 6H, –C₂H₄–(CH₂)₃CH₃), 1.56 (br s, 2H, –CH₂–CH₂–C₄H₉), 2.42 (s, 3H, –CH₃, –Tol), 4.01 (t, 2H, ³J = 7.4 Hz, –CH₂C₅H₁₁), 5.42 (s, 2H, NH₂), 5.77 (s, 1H, COCH=), 7.13 (dd, 1H, ³J = 9.0 Hz, ⁴J = 2.5 Hz, Ar), 7.37 (s, 4H, Tol), 7.39 (d, 1H, ⁴J = 2.5 Hz, Ar), 7.59 (d, 1H, ³J = 9.0 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 13.69, 20.82 (2CH₃), 21.72, 25.28, 28.11, 30.31, 47.14 (5CH₂), 106.27, 109.57, 118.28, 120.90 (4CH), 128.26 (2CH, –Tol), 128.39 (C), 129.07 (2CH, –Tol), 131.90, 133.37, 138.56, 145.12, 152.37, 174.84 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3329 (w), 3223 (m), 2918 (m), 1644 (w), 1587 (s), 1562 (s), 1491 (s), 1413 (m), 1372 (m), 1279 (m), 1179 (m), 1107 (m), 1016 (m), 936 (m), 823 (s), 720 (m), 559 (m). MS (GC, 70 eV): m/z (%) = 335 (M⁺¹, 25), 334 (M⁺, 100), 263 (61), 250 (23), 248 (32), 221 (10), 147 (9), 43 (11). HRMS (ESI): calcd for C₂₂H₂₆N₂O: 334.2040, found: 334.2043.

6-Amino-1-cyclohexyl-2-p-tolylquinolin-4(1H)-one (8af). Brown powder, yield 68%. Mp 108–110 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.90 (br d, 2H, ³J = 6.9 Hz, cyclohexyl), 1.26 (br s, 2H, cyclohexyl), 1.52 (br d, 2H, ³J = 12.0 Hz, cyclohexyl), 1.78 (t, 4H, ³J = 10.1 Hz, cyclohexyl), 2.43 (s, 3H, –Tol), 4.07 (t, 1H, ³J = 12.3 Hz, cyclohexyl), 5.41 (br s, 2H, –NH₂), 5.72 (s, 1H, –COCH=), 7.08 (dd, 1H, ³J = 9.2 Hz, ⁴J = 2.8 Hz, Ar), 7.38 (s, 5H, Ar), 7.91 (d, 1H, ³J = 9.2 Hz, Ar). ¹³C NMR (300.13 MHz DMSO-d₆): δ = 20.87 (CH₃, –Tol), 24.20 (CH₂), 26.22, 30.22 (4CH₂), 62.55 (CH, cyclohexyl), 106.35, 109.98, 119.95, 120.42 (4CH), 127.51, 129.19 (4CH), 129.26, 131.79, 134.54, 138.54, 144.79, 153.39, 174.69 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3326 (w), 2922 (m), 2851 (w), 1584 (s), 1557 (s), 1510 (m), 1482 (s), 1446 (m), 1394 (m), 1254 (m), 1167 (m), 1113 (w), 1052 (w), 822 (s), 596 (m), 563 (m). MS (GC, 70 eV): m/z (%) = 332 (M⁺, 33), 251 (17), 250 (100), 249 (13), 55 (12). HRMS (EIHR): calcd for C₂₂H₂₄N₂O: 332.1883, found: 332.1885.

6-Amino-1-pentyl-2-p-tolylquinolin-4(1H)-one (8ag). Yellow crystals, yield 99%. Mp 218–219 °C. ¹H NMR (300, 13 MHz, DMSO-d₆): δ = 0.73 (t, 3H, –CH₃, –C₄H₈–CH₃), 1.05 (s, 4H, –C₂H₄–C₂H₂–CH₃), 1.56 (s, 2H, –CH₂–CH₂–C₃H₇), 2.41 (s, 3H, CH₃, –Tol), 3.99 (t, 2H, –CH₂–C₄H₉), 5.40 (s, 2H, NH₂), 5.74 (s, 1H, –COCH=), 7.11 (d, 1H, ³J = 7.0 Hz, Ar), 7.36 (s, 4H, –Tol + 1H, Ar), 7.57 (d, 1H, ³J = 9.0 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.58, 20.83 (2CH₃), 21.33, 27.84, 27.94, 47.21 (4CH₂), 106.26, 109.59, 118.29, 120.88 (4CH), 128.25 (2CH), 128.39 (C), 129.08 (2CH), 131.88, 133.38, 138.57, 145.11, 152.38, 174.82 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3379 (w), 3221 (m), 2921 (m), 1588 (s), 1563 (s), 1492 (s), 1414 (m), 1377 (m), 1281 (m), 1179 (m), 1019 (m), 822 (s), 558 (m). MS (GC, 70 eV): m/z (%) = 321 (M⁺¹, 23), 320 (M⁺, 100), 264 (13), 263 (78), 262 (10), 250 (27), 249 (17), 248 (43), 221 (11), 207 (10), 147 (13). HRMS (ESI-TOF): calcd for C₂₁H₂₄N₂O: 320.1882, found: 320.1889.

6-Amino-1-n-butyl-2-p-tolyl-4-quinolone (8ah). Yellow crystals, yield 99%. Mp 206–208 °C. ¹H NMR (250.13 MHz, DMSO): δ = 0.69 (t, ³J = 7.3 Hz, 3H, CH₃CH₂CH₂CH₂–), 1.08 (dd, J = 14.7, 7.3 Hz, 2H, CH₃CH₂CH₂CH₂–), 1.51–1.61 (m, 2H, CH₃CH₂CH₂CH₂–), 2.42 (s, 3H, Ar–CH₃), 3.99–4.04 (m, 2H, CH₃CH₂CH₂CH₂–), 5.42 (s, 2H, –NH₂), 5.76 (s, 1H, Ar), 7.12 (dd, ^3,4J = 9.1, 2.7 Hz, 1H, Ar), 7.38 (s, 5H, Ar), 7.60 (d, ³J = 9.1 Hz, 1H, Ar). ¹³C NMR (75 MHz, DMSO) δ = 13.23 (CH₃), 19.00 (CH₂), 20.84 (CH₃), 30.44, 47.04 (2CH₂), 106.24, 109.59, 118.35, 120.91 (4CH), 128.28 (2CH), 128.38 (C), 129.10 (2CH), 131.90, 133.37, 138.59, 145.12, 152.43, 174.84 (7C). IR (ATR): [small nu, Greek, tilde] = 3376 (w), 3330 (w), 3222 (w), 2951 (w), 2855 (w), 1650 (w), 1612 (w), 1587 (s), 1562 (s), 1542 (s), 1510 (m), 1492 (s), 1456 (m), 1416 (s), 1375 (m), 1328 (m), 1307 (m), 1283 (s), 1256 (m), 1231 (w), 1207 (w), 1180 (s), 1155 (w), 1109 (w), 1072 (w), 1016 (m), 935 (w), 867 (w), 852 (w), 835 (s), 824 (s), 815 (s), 789 (w), 776 (m), 738 (w), 700 (w), 688 (w), 595 (m), 555 (s), 533 (s). MS (GS): m/z (%) = 306 (M⁻¹, 100), 307 (25), 264 (15), 263 (74), 253 (10), 250 (18), 249 (18), 248 (30), 209 (11), 208 (14), 207 (24), 147 (12). HRMS (ESI): calcd for C₂₀H₂₃N₂O: 307.18049, found: 307.18102.

6-Amino-1-n-propyl-2-p-tolyl-4-quinolone (8ai). Pale brown crystals, yield 97%. Mp 210–212 °C. ¹H NMR (250.13 MHz, DMSO): δ = 0.66 (t, ³J = 7.4 Hz, 3H, CH₃CH₂CH₂–), 1.60 (dd, J = 14.8, 7.4 Hz, 2H, CH₃CH₂CH₂–), 2.42–2.55 (m, 3H, Ar–CH₃), 3.94–3.99 (m, 2H, –NH₂), 5.42 (s, 2H, CH₃CH₂CH₂–), 5.76 (s, 1H, –COCH=), 7.12 (dd, ^3,4J = 9.1, 2.7 Hz, 1H, Ar), 7.37–7.39 (m, 5H, Ar), 7.60 (d, ³J = 9.1 Hz, 1H, Ar). ¹³C NMR (75 MHz, DMSO) δ = 10.57, 20.84 (2CH₃), 21.80, 48.80 (2CH₂), 106.22, 109.55, 118.39, 120.93 (4CH), 128.23 (2CH), 128.33 (C), 129.13 (2CH), 131.90, 133.40, 138.60, 145.15, 152.51, 174.87 (6C). IR (ATR): [small nu, Greek, tilde] = 3428 (w), 3329 (w), 3226 (w), 2938 (w), 1622 (w), 1582 (s), 1566 (s), 1510 (w), 1483 (s), 1376 (w), 1360 (w), 1316 (w), 1281 (m), 1259 (w), 1179 (m), 1112 (w), 1070 (w), 1014 (w), 934 (w), 902 (w), 876 (w), 845 (w), 808 (s), 741 (w), 715 (w), 688 (w), 625 (w), 593 (m), 568 (m), 550 (m), 531 (m). MS (GS): m/z (%) = 292 (M⁻¹, 100), 293 (21), 264 (16), 263 (78), 250 (11), 249 (18), 248 (42), 221 (10), 147 (11). HRMS (ESI): calcd for C₁₉H₂₁N₂O: 293.16484, found: 293.16533.

6-Amino-1-isopropyl-2-p-tolylquinolin-4(1H)-one (8aj). Yellow crystals, yield 85%. Mp 323–324 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 1.54 (d, 6H, ³J = 7.1 Hz, 2CH₃, i-PrOH), 2.42 (s, 3H, CH₃, –Tol), 4.57 (m, 1H, CH, i-PrOH), 5.44 (br s, 2H, NH₂), 5.71 (s, 1H, –COCH=), 7.09 (dd, 1H, ³J = 9.2 Hz, ⁴J = 2.8 Hz, Ar), 7.38 (m, 1H, Ar + 4H, –Tol), 7.80 (d, 1H, ³J = 7.1 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO) δ = 20.82 (2CH₃), 53.06 (CH₃, –Tol), 106.54, 109.78, 119.98, 120.19 (4CH), 127.63 (2CH), 127.72 (C), 129.32 (2CH), 129.39 (CH), 131.08, 134.43, 138.57, 144.83, 153.12, 174.70 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3318 (w), 2919 (w), 1586 (s), 1568 (s), 1485 (m), 1454 (m), 1393 (m), 1373 (m), 1248 (m), 1170 (m), 1109 (m), 1076 (m), 995 (m), 824 (s), 595 (m). MS (GC, 70 eV): m/z (%) = 293 (M⁺¹, 14), 292 (M⁺, 63), 251 (28), 250 (100), 222 (22), 221 (21), 206 (13). HRMS (ESI): calcd for C₁₉H₂₀N₂O: 292.1570, found: 292.1570.

6-Amino-1-phenyl-2-p-tolylquinolin-4(1H)-one (8ak). Brown powder, 81% (yield of the product 8ak obtained from the substrate 7ak) 56% (yield of the product 8ak obtained from the substrate 7aq). Mp 253–255 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 2.24 (–CH₃, –Tol), 5.42 (br s, 2H, –NH₂), 5.97 (s, 1H, –COCH=), 6.59 (d, 1H, ³J = 9.1 Hz, Ar), 6.92 (dd, 1H, ³J = 2.8 Hz, ³J = 9.1 Hz, Ar), 7.05 (d, 2H, ³J = 8.0 Hz, –Tol), 7.19 (d, 2H, ³J = 8.0 Hz, –Tol), 7.32–7.35 (m, 1H, Ar), 7.36–7.38 (m, 2H, Ar), 7.40 (d, 2H, ³J = 2.8 Hz, Ar), 7.42–7.44 (m, 1H, Ar). ¹³C NMR (300.13 MHz, DMSO) δ = 20.65 (CH₃), 105.66, 109.43, 119.01, 120.57 (4CH), 127.07 (C), 128.25 (2CH), 128.29 (C), 128.68 (CH), 129.04, 129.33, 130.07 (6CH), 133.11, 134.18, 137.66, 139.24, 145.35, 151.92, 175.48 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3326 (w), 1587 (s), 1568 (s), 1506 (m), 1480 (s), 1403 (m), 1373 (m), 1319 (m), 1293 (m), 1022 (m), 926 (w), 853 (m), 820 (s), 769 (m), 698 (s), 578 (m), 544 (m). MS (GC, 70 eV): m/z (%) = 327 (M⁺¹, 22), 326 (M⁺, 100), 298 (27). HRMS (ESI-TOF): calcd for C₂₂H₁₈N₂O: 326.1414, found: 326.1409.

6-Amino-1-(3,5-dimethylphenyl)-2-p-tolylquinolin-4(1H)-one (8am). Yellow crystals, yield 85%. Mp 332–334 °C. ¹H NMR (300 MHz, DMSO-d₆): δ = 2.23 (s, 6H, 2CH₃, Ar′), 2.25 (s, 3H, –CH₃, –Tol), 5.42 (s, 2H, –NH₂), 5.95 (s, 1H, –COCH=), 6.64 (d, 1H, ³J = 9.1 Hz, Ar), 6.93 (dd, 1H, ³J = 9.1 Hz, ⁴J = 2.7 Hz, Ar), 6.96–7.00 (m, 3H, Ar′), 7.06 (d, 2H, ³J = 8.0 Hz, –Tol), 7.21 (d, 2H, ³J = 8.0 Hz, –Tol), 7.40 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (250 MHz, DMSO-d₆): δ = 20.55, 20.68, 48.57 (3CH₃), 105.59, 109.44, 119.23, 120.56 (4CH), 127.06 (C), 127.49, 128.21, 128.99 (6CH), 130.03 (CH), 133.18, 134.21, 137.64 (3C), 138.53 (2C), 139.05, 145.31, 151.87, 175.43 (4C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3324 (m), 1584 (s), 1510 (m), 1478 (s), 1409 (m), 1323.9 (m), 1310 (m), 1180 (m), 1019 (m), 843 (m), 816 (m), 707 (m), 600 (m), 562 (m). MS (GC, 70 eV): m/z (%) = 355 (M⁺¹, 29), 354 (M⁺, 100), 353 (M⁻¹, 28), 115 (11). HRMS (ESI-TOF): calcd for C₂₄H₂₂N₂O: 354.1727, found: 354.1725.

6-Amino-1-(2,3-dihydro-1H-inden-5-yl)-2-p-tolylquinolin-4(1H)-one (8an). Brown powder, yield 31%. Mp 333–335 °C. ¹H NMR (300, 13 MHz, DMSO-d₆): δ = 0.84 (br s, 2H, Alk), 1.43 (br s, 2H, Alk), 2.39 (s, 3H, CH₃, –Tol), 3.90 (t, 2H, ³J = 7.1 Hz, Alk), 5.41 (s, 2H, –NH₂), 5.73 (s, 1H, –COCH=), 7.10 (dd, 1H, ³J = 9.1 Hz, Ar), 7.23–7.42 (m, 8H, Ar), 7.51 (d, 1H, ³J = 9.1 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 22.01 (CH₃), 26.92, 30.67, 53.12 (3CH₂), 111.50, 121.98 (2CH), 122.57 (CH + CF₃COOD), 122.82 (CH), 123.38, 123.76 (2C), 129.40 (2CH), 129.51, 129.54 (2CH), 131.76 (2CH), 132.06 (C), 132.31 (CH), 141.49, 144.20, 159.84, 161.72, 163.15, 164.08, 170.39 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3322 (w), 2938 (w), 1586 (s), 1568 (s), 1485 (s), 1470 (s), 1380 (m), 1283 (m), 1259 (m), 1176 (m), 1017 (m), 933 (w), 811 (s), 553 (m), 531 (m). HRMS (ESI-TOF): calcd for C₂₅H₂₂N₂O: 366.4508, found: 366.4485.

6-Amino-1-(4-methoxyphenyl)-2-p-tolylquinolin-4(1H)-one (8ap). Yellow powder, yield 85%. Mp 228–230 °C. ¹H NMR (500.13 MHz, DMSO-d₆): δ = 2.24 (s, 3H, –CH₃, –Tol), 3.76 (s, 3H, –OCH₃), 5.37 (br s, NH₂), 5.98 (s, 1H, –COCH=), 6.62 (d, 1H, ³J = 9.0 Hz, Ar), 6.93 (d, 2H, ³J = 8.9 Hz, –Tol), 6.94 (d, 1H, ³J = 9.0 Hz, Ar), 7.06 (d, 2H, ³J = 7.9 Hz, Ar′), 7.18 (d, 2H, ³J = 7.9 Hz, Ar′), 7.24 (d, 2H, ³J = 8.9 Hz, –Tol), 7.41 (d, 1H, ⁴J = 2.7 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 20.68, 55.26 (2CH₃), 105.67, 109.43 (2CH), 114.38 (2CH), 119.13, 120.61 (2CH), 127.14 (C), 128.31, 129.03, 131.08 (6CH), 131.90, 133.30, 134.63, 137.61, 145.34, 152.30, 158.70, 175.51 (8C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2918 (w), 1588 (s), 1568 (s), 1505 (s), 1481 (s), 1393 (m), 1361 (m), 1295 (m), 1245 (s), 1107 (m), 1023 (m), 818 (s), 546 (m). MS (GC, 70 eV): m/z (%) = 357 (M⁺¹, 29), 356 (M⁺, 100), 355 (M⁻¹, 13), 328 (12), 197 (10). HRMS (ESI-TOF): calcd for C₂₃H₂₀N₂O₂: 356.1519, found: 356.1525.

6-Amino-1-(3,4-dimethoxyphenethyl)-2-phenylquinolin-4(1H)-one (8ba). Yellow crystals, yield 81%. Mp 217–219 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 2.81 (t, 2H, ³J = 7.2 Hz, –CH₂–Ar), 3.58 (s, 3H, –OCH₃), 3.71 (s, 3H, –OCH₃), 4.19 (t, 2H, ³J = 7.2 Hz, –CH₂–CH₂Ar), 5.49 (br s, 2H, –NH₂), 5.75 (s, 1H, COCH=), 6.27 (d, 1H, ⁴J = 1.8 Hz, Ar′), 6.34 (dd, 1H, ³J = 8.1 Hz, ⁴J = 1.8 Hz, Ar′), 6.76 (d, 1H, ³J = 8.1 Hz, Ar′), 7.21 (dd, 1H, ³J = 9.1 Hz, ⁴J = 2.8 Hz, Ar), 7.30 (m, 2H, Ph), 7.44 (d, 1H, ⁴J = 2.8 Hz, Ar), 7.52 (m, 3H, Ph), 7.79 (d, 1H, ³J = 9.1 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 33.86, 49.07 (2CH₂), 55.20, 55.52 (2OCH₃), 106.30, 109.46, 111.82, 112.10, 118.49, 120.47, 121.13 (7CH), 128.32 (2CH, Ph), 128.36 (C), 128.38 (2CH, Ph), 128.96 (CH, Ph), 129.88, 131.76, 136.03, 145.24, 147.53, 148.59, 152.41, 174.93 (8C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3383 (w), 3310 (w), 3216 (w), 2953 (w), 1633 (w), 1589 (s), 1564 (s), 1489 (s). 1418 (m), 1311 (m), 1235 (s), 1177 (m), 1153 (s), 1028 (s), 938 (m), 883 (w), 807 (s), 754 (s), 706 (s), 623 (m), 543 (m). MS (GC, 70 eV): m/z (%) = 400 (M⁺, 28), 250 (15), 249 (100), 248 (16). HRMS (ESI): calcd for C₂₅H₂₄N₂O₃: 400.1778, found: 400.1787.

6-Amino-1-phenethyl-2-phenylquinolin-4(1H)-one (8bc). Yellow crystals, yield 99%. Mp 253–254 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 2.90 (t, 2H, ³J = 7.5 Hz, –CH₂–CH₂–, Ar′), 4.20 (t, 2H, ³J = 7.5 Hz, –CH₂–CH₂–, Ar′), 5.47 (s, 2H, –NH₂), 5.74 (s, 1H, –COCH=), 6.80–6.87 (m, 2H, Ar), 7.15–7.25 (m, 4H, Ar), 7.30–7.37 (m, 2H, Ar), 7.43 (d, 1H, ⁴J = 2.7 Hz, Ar), 7.49–7.56 (m, 3H, Ar), 7.78 (d, 1H, ³J = 9.1 Hz, Ar). ¹³C NMR (0.13 MHz, DMSO-d₆): δ = 34.30, 48.82 (2CH₂), 106.37, 109.53, 118.41, 121.13, 126.54 (5CH), 128.32, 128.39, 128.48, 128.53 (8CH, C), 129.06 (CH), 131.72, 135.99, 137.54, 145.26, 152.36, 174.90 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3368 (w), 1583 (s), 1488 (s), 1420 (m), 1371 (w), 1311 (m), 1177 (m), 1073 (w), 810 (m), 757 (m), 702 (s). MS (GC, 70 eV): m/z (%) = 341 (M⁺¹, 12), 340 (M⁺, 48), 250 (17), 249 (100), 248 (21). HRMS (ESI): calcd for C₂₃H₂₀N₂O: 340.1571, found: 340.1576.

6-Amino-1-phenethyl-2-phenylquinolin-4(1H)-one (8bd). Yellow crystals, yield 99%. Mp 223–225 °C. ¹H NMR (300.13 MHz, CDCl₃/DMSO-d₆ 9 : 1): δ = 1.92 (p, 2H, ³J = 7.5 Hz, –CH₂–CH₂–CH₂–Ph), 2.36–2.45 (m, 2H, –C₂H₄–CH₂–Ph), 3.30 (br s, NH₂ + H₂O) 3.94 (t, 2H, ³J = 7.8 Hz, –CH₂–C₂H₄–Ph), 5.98 (s, 1H, –COCH=), 6.90–7.61 (m, 13H, Ar). ¹³C NMR (300.13 MHz, CDCl₃/DMSO-d₆ 9 : 1): δ = 29.47, 31.87, 46.81 (3CH₂), 107.56, 110.14, 117.01, 121.04, 125.58 (5CH), 127.52, 127.59, 127.86 (6CH), 127.93 (C), 128.10 (2CH), 128.69 (CH), 132.45, 135.43, 139.46, 143.57, 152.36, 175.65. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3225 (w), 1562 (s), 1489 (s), 1417 (m), 1369 (m), 1283 (m), 1186 (m), 838 (s), 741 (m), 698 (s), 561 (m). MS (GC, 70 eV): m/z (%) = 355 (M⁺¹, 27), 354 (M⁺, 100), 250 (12), 249 (82), 248 (19), 236 (16), 235 (10), 147 (10), 91 (38). HRMS (ESI-TOF): calcd for C₂₄H₂₂N₂O: 354.1721, found: 354.1732.

6-Amino-1-heptyl-2-phenylquinolin-4(1H)-one (8be). Yellow crystals, yield 75%. Mp 178–180 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.81 (t, 3H, ³J = 6.9 Hz, –CH₃), 0.99–1.29 (m, 8H, –(CH₂)₂(CH₂)₄CH₃), 1.57 (br s, 2H, –CH₂–CH₂–C₅H₁₁), 3.26–3.66 (br s, 2H, –NH₂ + H₂O), 4.00 (t, 2H, ³J = 7.1 Hz, –CH₂–C₆H₁₃), 5.79 (s, 1H, –COCH=), 7.13 (d, 1H, ³J = 7.1 Hz, Ar), 7.39 (d, 1H, ⁴J = 1.8 Hz, Ar), 7.47–7.67 (m, 1H, Ar + 5H, Ph). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 13.78 (CH₃), 21.85, 25.55, 27.70, 28.14, 30.82, 47.25 (6CH₂), 106.22, 109.50, 118.30, 121.04 (4CH), 128.35 (C + 2CH, Ph), 128.55 (2CH, Ph), 129.07 (CH, Ph), 131.89, 136.14, 145.19, 152.27, 174.82 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3387 (w), 3328 (w), 3222 (m), 3061 (w), 2918 (m), 2852 (m), 1643 (w), 1605 (m), 1585 (s), 1558 (s), 1538 (s), 1489 (s), 1440 (m), 1415 (s), 1376 (m), 1328 (m), 1307 (m), 1282 (s), 1254 (m), 1229 (m), 1153 (m), 1116 (m), 1073 (m), 1020 (m), 938 (m), 868 (m), 837 (s), 815 (s), 787 (m), 758 (m), 721 (m), 702 (s), 662 (m), 623 (m), 558 (s), 538 (s). MS (GC, 70 eV): m/z (%) = 335 (M⁺¹, 33), 334 (M⁺, 100), 250 (18.39), 249 (89), 236 (34), 235 (14), 41 (10). HRMS (ESI): calcd for C₂₂H₂₆N₂O: 334.2039, found: 334.2045.

6-Amino-1-cyclohexyl-2-phenylquinolin-4(1H)-one (8bf). Yellow crystals, yield 99%. Mp 261–263 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.86 (q, 2H, ³J = 12.6 Hz, cyclohexyl), 1.26 (q, 1H, ³J = 12.8 Hz, cyclohexyl), 1.51 (d, 1H, ³J = 12.7 Hz, cyclohexyl), 1.78 (t, 4H, ³J = 12.4 Hz, cyclohexyl), 2.40 (q, 2H, ³J = 12.1 Hz, cyclohexyl), 4.02 (t, 1H, ³J = 12.6 Hz, cyclohexyl), 5.42 (s, 2H, –NH₂), 5.74 (s, 1H, –COCH=), 7.09 (dd, 1H, ³J = 9.2 Hz, ⁴J = 2.9 Hz, Ar), 7.40 (d, 1H, ⁴J = 2.9 Hz, Ar), 7.43–7.70 (m, 5H, –Ph), 7.91 (d, 1H, ³J = 9.2 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆ 9 : 1): δ = 24.19 (CH₂), 26.23, 30.18 (4CH₂), 62.62, 106.35, 109.84, 120.00, 120.41 (5CH), 127.60, 128.66 (4CH), 129.08 (CH), 129.19, 131.74, 137.34, 144.84, 153.24, 174.68 (6C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3314 (w), 2939 (w), 1583 (s), 1486 (s), 1402 (m), 1348 (m), 1260 (m), 1167 (m), 1053 (m), 779 (s), 702 (s), 565 (m). MS (GC, 70 eV): m/z (%) = 318 (M⁺, 23), 237 (18), 236 (100), 235 (9), 208 (10), 41 (8). HRMS (ESI-TOF): calcd for C₂₁H₂₂N₂O: 318.1726, found: 318.1732.

6-Amino-1-hexyl-2-phenylquinolin-4(1H)-one (8bg). Yellow crystals, yield 80%. Mp 197–199 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.77 (t, 3H, ³J = 7.0 Hz, –(CH₂)₅–CH₃), 0.96–1.11 (m, 6H, –(CH₂)₂–(CH₂)₃–CH₃), 1.57 (br s, 2H, –CH₂–CH₂–C₄H₉), 3.98 (t, 2H, ³J = 7.2 Hz, –CH₂–C₅H₁₁), 5.43 (s, 2H, –NH₂), 5.78 (s, 1H, –COCH=), 7.13 (dd, 1H, ³J = 9.0 Hz, ⁴J = 2.2 Hz, Ar), 7.39 (d, 1H, ⁴J = 2.2 Hz, Ar), 7.49–7.61 (m, 1H, Ar + 5H, Ph). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 13.68 (–CH₃), 21.71, 25.27, 28.12, 30.25, 47.22 (5CH₂), 106.25, 109.50, 118.30, 120.95 (4CH), 128.37, 128.57 (4CH, –Tol), 129.07 (CH, –Tol), 131.87, 136.17, 145.16, 152.25 (4C), 174.83 (–CO–). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3222 (w), 2916 (w), 1558 (s), 1489 (s), 1416 (m), 1376 (m), 1283 (m), 1178 (m), 837 (s), 760 (m), 702 (s), 558 (m). MS (GC, 70 eV): m/z (%) = 321 (M⁺¹, 24), 320 (M⁺, 100), 250 (14), 249 (77), 248 (17). HRMS (ESI-TOF): calcd for C₂₁H₂₄N₂O: 320.1882, found: 320.1889.

6-Amino-2-butyl-1-(3,4-dimethoxyphenethyl)quinolin-4(1H)-one (8ca). Brown oil, yield 99%. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.91 (t, 3H, ³J = 7.2 Hz, –(CH₂)₃–CH₃), 1.30–1.40 (m, 2H, –(CH₂)₂–CH₂–CH₃), 1.52 (p, 2H, ³J = 7.2 Hz, –CH₂–CH₂–C₂H₅), 2.44 (t, 2H, ³J = 7.5 Hz, –CH₂–C₃H₇), 2.96 (t, 2H, ³J = 6.0 Hz, –CH₂–CH₂–Ar′), 3.71 (s, 3H, –OCH₃), 3.75 (s, 3H, –OCH₃), 4.36 (br s, 2H, –CH₂–CH₂–Ar′), 5.35 (br s, 2H, –NH₂), 5.82 (s, 1H, –COCH=), 6.69–6.79 (m, 2H, Ar′), 6.90 (d, 1H, ³J = 7.9 Hz, Ar′), 7.12 (dd, 1H, ³J = 9.1 Hz, ⁴J = 2.7 Hz, Ar), 7.36 (d, 1H, ⁴J = 2.7 Hz, Ar), 7.68 (d, 1H, ³J = 9.1 Hz, Ar). ¹³C NMR (300 MHz, DMSO-d₆): δ = 13.55 (–(CH₂)₃–CH₃), 21.87, 30.38, 32.41, 33.93, 46.82 (5CH₂), 55.34, 55.53 (2OCH₃), 106.48, 107.84, 111.96, 112.72, 117.83, 120.73, 120.79 (7CH), 127.98, 130.30, 132.17, 144.74, 147.65, 148.69, 152.89, 175.28. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3325 (w), 3211 (w), 2929 (w), 1587 (s), 1481 (s), 1362 (w), 1323 (w), 1235 (s), 1139 (m), 1024 (s), 808 (m), 761 (m), 557 (m). MS (GC, 70 eV): m/z (%) = 381 (M⁺¹, 15), 380 (M⁺, 55), 379 (M⁻¹, 14), 230 (16), 229 (100), 214 (12), 174 (11), 159 (12), 151 (18). HRMS (ESI-TOF): calcd for C₂₃H₂₈N₂O₃: 380.2091, found: 380.2099.

6-Amino-1-(3,4-dimethoxyphenethyl)-2-pentylquinolin-4(1H)-one (8da). Brown oil, yield 98%. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.89 (t, 3H, ³J = 7.2 Hz, –(CH₂)₄–CH₃), 1.28–1.34 (m, 4H, –(CH₂)₂–(CH₂)₂–CH₃), 1.53 (br s, 2H, –CH₂–CH₂–C₃H₇), 2.43 (t, 2H, ³J = 7.5 Hz, –CH₂–C₄H₉), 2.96 (t, 2H, ³J = 6.4 Hz, –CH₂–CH₂–Ar′), 3.71 (s, 3H, –OCH₃), 3.75 (s, 3H, –OCH₃), 4.36 (br s, 2H, –CH₂–CH₂–Ar′), 5.35 (br s, 2H, –NH₂), 5.82 (s, 1H, –COCH=), 6.69–6.79 (m, 2H, Ar′), 6.89 (d, 1H, ³J = 7.9 Hz, Ar′), 7.12 (dd, 1H, ³J = 9.1 Hz, ⁴J = 2.7 Hz, Ar), 7.36 (d, 1H, ⁴J = 2.7 Hz, Ar), 7.68 (d, 1H, ³J = 9.1 Hz, Ar). ¹³C NMR (300 MHz, DMSO-d₆): δ = 13.82 (–(CH₂)₃–CH₃), 21.75, 27.91, 30.91, 32.65, 33.93, 46.80 (6CH₂), 55.32, 55.52 (2OCH₃), 106.48, 107.81, 111.93, 112.71, 117.83, 120.73, 120.79 (7CH), 127.98, 130.30, 132.16, 144.74, 147.65, 148.69, 152.88, 175.28. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3328 (w), 3213 (w), 2928 (w), 1588 (s), 1482 (s), 1362 (w), 1323 (w), 1235 (s), 1139 (m), 1024 (s), 808 (m), 761 (m), 557 (m). MS (GC, 70 eV): m/z (%) = 395 (M⁺¹, 19), 394 (M⁺, 47), 281 (18), 267 (13), 244 (11), 243 (100), 237 (11), 228 (20), 208 (12), 188 (13), 187 (28), 175 (10), 174 (10), 165 (13), 164 (22), 160 (11), 159 (19), 151 (31), 133 (12), 107 (11), 106 (11), 105 (17), 103 (15), 79 (19), 77 (17), 73 (11). HRMS (ESI-TOF): calcd for C₂₄H₃₀N₂O₃: 394.2245, found: 394.2256.

6-Amino-1-(4-methoxybenzyl)-2-pentylquinolin-4(1H)-one (8db). Beige crystals, yield 99%. Mp 201–202 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.86 (t, 3H, ³J = 7.0 Hz, –C₄H₈–CH₃), 1.19–1.39 (m, 4H, –C₂H₄–C₂H₄–CH₃), 1.60 (p, 2H, ³J = 7.7 Hz, –CH₂–CH₂–C₃H₇), 2.67 (t, 2H, ³J = 7.7 Hz, –CH₂–C₄H₉), 3.73 (s, 3H, –OCH₃), 5.30 (s, 2H, –NH₂), 5.42 (s, 2H, –CH₂–Ar′), 5.98 (s, 1H, –COCH=), 6.86–7.04 (m, 5H, 1H, Ar + 4H, Ar′), 7.25–7.38 (m, 2H, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 13.74 (–C₄H₈–CH₃), 21.76, 28.07, 30.74, 32.95, 48.15 (5CH), 55.01 (–OCH₃), 106.20, 108.18 (2CH), 114.18 (2CH), 118.20, 120.47 (2CH), 126.65 (2CH), 127.87, 128.88, 132.79, 144.79, 153.01, 158.34, 175.47 (7C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3320 (w), 2951 (w), 1587 (s), 1564 (s), 1486 (s), 1366 (m), 1244 (m), 1174 (s), 1106 (m), 1027 (m), 818 (s), 622 (m), 555 (s). MS (GC, 70 eV): m/z (%) = 350 (M⁺, 11), 292 (8), 174 (16), 121 (100). HRMS (ESI-TOF): calcd for C₂₂H₂₆N₂O₂: 350.1988, found: 350.1994.

Specific procedure for the synthesis of 9a and 9b

Under a constant flow of an inert gas a pressure tube was charged with a magnetic stirrer, 6a (450 mg, 1 equiv.), KF (2 equiv.), extra dry dimethylformamide (6 mL) and appropriate amine (1.7 equiv.). After stirring for 10 h at 120 °C the solvent was evaporated under reduced pressure. Residue was purified by a column chromatography (silica gel, heptane/ethyl acetate, 25 : 1). On the TLC compound 9 appears as an upper spot (R_f ≈ 0.8) in comparison to 7 (R_f ≈ 0.4).

Specific procedure for the synthesis of 9c and 10a

Under a constant flow of an inert gas a pressure tube was charged with a magnetic stirrer, 6c (450 mg, 1 equiv.), KF (2 equiv.), extra dry dimethylformamide (6 mL) and 2-(3,4-dimethoxyphenyl)ethanamine (1.7 equiv.). After stirring for 4 h at 120 °C the solvent was evaporated under reduced pressure. Residue was purified by a column chromatography (silica gel, heptane/ethyl acetate, 25 : 1). On the TLC compound 9 and 10 appear as upper spots (R_f ≈ 0.8 for 9, R_f ≈ 0.75 for 10) in comparison to 7 (R_f ≈ 0.4).

Specific procedure for the synthesis of 9d and 10b

Under a constant flow of an inert gas a pressure tube was charged with a magnetic stirrer, 6c (450 mg, 1 equiv.), KF (2 equiv.), extra dry dimethylformamide (6 mL) and cyclohexylamine (1.7 equiv.). After stirring for 4 h at 120 °C the solvent was evaporated under reduced pressure. Residue was purified by a column chromatography (silica gel, heptane/ethyl acetate, 25 : 1).

(Z)-3-(4-Methoxybenzylamino)-1-(2-(4-methoxybenzylamino)-5-nitrophenyl)-3-p-tolylprop-2-en-1-one (9a). Yellow crystals, yield 8%. Mp 166–167 °C. ¹H NMR (300 MHz, CDCl₃) δ = 2.42 (s, 3H, CH₃), 3.80 (s, s, 6H, 2OCH₃), 4.41 (d, d, 6.0 Hz, 4H, 2CH₂), 5.79 (s, 1H, –CH=C), 6.59 (d, J = 9.4 Hz, 1H, Ar), 6.85–6.90 (m, 4H, Ar), 7.13–7.16 (m, 2H, Ar), 7.25–7.33 (m, 6H, Ar), 8.05 (dd, J = 9.3, 2.5 Hz, 1H, Ar), 8.58 (d, J = 2.6 Hz, 1H, Ar), 9.88 (t, J = 5.5 Hz, 1H, NH), 11.28 (t, J = 6.1 Hz, 1H, NH). ¹³C NMR (300 MHz, CDCl₃) δ = 21.34 (CH₃), 46.43, 48.08 (CH₂), 55.25, 94.20, 110.94, 114.16 (d, J = 4.9 Hz), 119.48, 126.32, 127.63, 128.40–127.75 (m), 129.38 (d, J = 10.8 Hz), 130.26, 132.26, 135.74, 139.97, 154.34, 158.97 (d, J = 1.7 Hz), 167.26, 189.67. IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3225 (w), 2838 (w), 1609 (m), 1576 (m), 1556 (m), 1514 (s), 1494 (m), 1456 (m), 1428 (w), 1369 (w), 1324 (s), 1303 (m), 1278 (m), 1253 (s), 1200 (m), 1176 (m), 1140 (m), 1106 (s), 1078 (m), 1020 (m), 927 (w), 911 (m), 848 (w), 819 (s), 806 (m), 786 (m), 762 (m), 739 (s), 723 (w), 712 (w), 690 (m), 666 (w), 651 (m), 631 (m), 611 (w), 557 (w), 550 (w). MS (GC, 70 eV): m/z (%) = 537 (M⁺, 2), 417 (34), 416 (100), 283 (61), 121 (88). HRMS (EI): calcd for C₃₂H₃₂N₃O₅: 538.2336, found: 538.2343.

(Z)-3-(Isopropylamino)-1-(2-(isopropylamino)-5-nitrophenyl)-3-p-tolylprop-2-en-1-one (9b). Brown oil, yield 7%. ¹H NMR (250 MHz, CDCl₃) δ = 1.22 (d, J = 6.5 Hz, 6H, CH(CH₃)₂), 1.34 (d, J = 6.4 Hz, 6H, CH(CH₃)₂), 2.42 (s, 3H, CH₃), 3.60–3.86 (m, 2H, CH(CH₃)₂), 5.61 (s, 1H, –CH=C), 6.61 (d, J = 9.5 Hz, 1H, Ar), 7.26–7.28 (m, 4H, tolyl), 8.08 (dd, J = 9.4, 2.6 Hz, 1H, Ar), 8.52 (d, J = 2.6 Hz, 1H, Ar), 9.51 (d, J = 7.1 Hz, 1H, NH), 10.88 (d, J = 9.3 Hz, 1H, NH). ¹³C NMR (250 MHz, CDCl₃) δ = 21.34, 22.52, 24.19, 43.89, 46.31 (5CH₃), 93.73, 110.52 (CH), 119.07 (C), 126.73, 127.33, 127.95, 129.26 (CH), 132.98, 134.94, 139.61, 153.60, 166.33, 189.50 (C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2930 (w), 1596 (s), 1572 (s), 1520 (s), 1475 (m), 1315 (s), 1241 (m), 1142 (m), 1137 (m), 1060 (m), 922 (w), 896 (w), 860 (w), 739 (s), 651 (w), 577 (w). HRMS (EI): calcd for C₂₂H₂₇N₃O₃: 381.4724, found: 381.4731.

(Z)-3-(3,4-Dimethoxyphenethylamino)-1-(2-(3,4-dimethoxyphenethylamino)-5-nitrophenyl)hept-2-en-1-one (9c). Brown oil, yield 9%. ¹H NMR (300 MHz, CDCl₃) δ = 0.94 (t, ³J = 7.2 Hz, 3H, –(CH₂)₃CH₃), 1.36–1.57 (m, 4H, –(CH₂)₃CH₃), 2.22 (t, ³J = 7.62, 2H, –(CH₂)₃CH₃), 2.91 (dt, ³J = 14.6, ³J = 7.2 Hz, 4H, 2(–NHCH₂CH₂–)), 3.45–3.60 (m, 4H, 2(–NHCH₂CH₂–)), 3.85 (s, 12H, –OCH₃), 5.59 (s, 1H, –CH=), 6.60 (d, ³J = 9.4 Hz, 1H, Ar), 6.75–6.84 (m, 6H, Ph), 8.10 (dd, ³J = 9.3 Hz, ⁴J = 2.6 Hz, 1H, Ar), 8.52 (d, ⁴J = 2.6 Hz, 1H, Ar), 9.52 (t, ³J = 5.2 Hz, 1H, NH), 11.21 (t, ³J = 5.8 Hz, 1H, NH). ¹³C NMR (75 MHz, CDCl₃) δ = 13.80 (CH₃), 22.70, 30.41, 32.45, 35.00, 36.56, 44.85, 45.05 (7CH₂), 55.83, 55.92 (4CH₃), 91.84, 110.20, 111.45, 111.47, 112.19, 112.22 (6CH), 119.59 (C), 120.68, 120.78, 126.09, 127.83 (4CH), 130.70, 131.35, 135.51, 147.81, 147.97, 148.99, 149.05, 154.19, 169.32, 189.04 (10C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2931 (w), 1602 (m), 1574 (m), 1513 (s), 1463 (m), 1417 (w), 1318 (m), 1258 (s), 1233 (s), 1139 (s), 1123 (s), 1023 (s), 914 (w), 804 (m), 762 (m), 747 (m), 635 (w). MS (GC, 70 eV): m/z (%) = 591 (M⁻¹, 2), 441 (24), 440 (88), 281 (13), 208 (10), 207 (46), 169 (20), 166 (14), 165 (100), 164 (42), 152 (22), 151 (75), 150 (15), 131 (13), 119 (13), 107 (16), 105 (18), 103 (10), 98 (12), 97 (16), 91 (21), 85 (10), 84 (15), 83 (15), 82 (13), 81 (25), 80 (12), 79 (23), 78 (15), 77 (20), 73 (26), 71 (13), 70 (13), 69 (49), 68 (15), 67 (16), 66 (11), 65 (12), 64 (10), 60 (42), 57 (25), 56 (21), 55 (40), 54 (14), 53 (12), 52 (18), 51 (14), 50 (10), 48 (10), 46 (29). HRMS (ESI): calcd for C₃₃H₄₂N₃O₇: 592.3017, found: 592.3018.

(Z)-3-(Cyclohexylamino)-1-(2-(cyclohexylamino)-5-nitrophenyl)hept-2-en-1-one (9d). Brown oil, yield 36%. ¹H NMR (500 MHz, CDCl₃) δ = 0.98 (t, ³J = 7.3 Hz, 3H, CH₃), 1.37–1.47 (m, 11H, cyclohexyl), 1.59–1.64 (m, 5H, cyclohexyl), 1.79–1.83 (m, 4H, cyclohexyl), 1.92–1.94 (d, m, 2H, –CH₂CH₂CH₂CH₃), 2.03–2.04 (m, 2H, –CH₂CH₂CH₂CH₃), 2.30–2.34 (m, 2H, –CH₂CH₂CH₂CH₃), 3.42–3.46 (m, 2H, cyclohexyl), 5.55 (s, 1H, –CH=C), 6.58 (d, J = 9.7 Hz, 1H, Ar), 8.05 (dd, ³J = 9.4 Hz, ⁴J = 2.7 Hz, 1H, Ar), 8.52 (d, ⁴J = 2.7 Hz, 1H, Ar), 9.50 (d, J = 7.2 Hz, 1H, NH), 11.19 (d, J = 8.8 Hz, 1H, NH). ¹³C NMR (500 MHz, CDCl₃) δ = 13.83 (CH₃), 22.75, 24.69, 25.27, 25.69, 31.23, 32.40, 32.57, 34.28 (13CH₂), 51.12, 51.88, 91.48, 110.37 (4CH), 119.47 (C), 126.47, 127.67 (2CH), 134.85, 153.50, 168.08, 188.96 (4C). IR (ATR): [small nu, Greek, tilde] = 2926 (m), 2852 (w), 1598 (s), 1570 (s), 1522 (m), 1489 (m), 1448 (w), 1310 (s), 1256 (s), 1206 (m), 1150 (m), 1121 (s), 1097 (s), 921 (w), 888 (w), 816 (m), 747 (m), 718 (m), 650 (m). MS (GS): m/z (%) = 427 (M⁺, 34), 410 (23), 345 (23), 344 (100), 327 (13), 326 (50), 302 (12), 245 (37), 203 (10), 180 (20), 165 (11), 84 (11), 55 (34), 41 (19). HRMS (ESI): calcd for C₂₅H₃₇O₃N₃: 427.2829, found: 427.2827.

(Z)-1-(2-Chloro-5-nitrophenyl)-3-(3,4-dimethoxyphenethylamino)hept-2-en-1-one (10a). Brown oil, yield 39%. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.92 (t, 3H, ³J = 7.2 Hz, –CH₃, –n-But), 1.33–1.38 (m, 2H, –CH₂–, –n-But), 1.44–1.52 (m, 2H, –CH₂–, –n-But), 2.13–2.21 (m, 2H, –CH₂–, –n-But), 2.89 (t, 3H, –CH₂–, R₁), 2.99 (3H, –OCH₃), 3.51–3.58 (m, 3H, –CH₂–, R₁), 3.82–3.86 (m, 3H, –OCH₃), 5.32 (s, 1H, –CH=), 6.73–6.82 (m, 4H, Ar), 8.06 (dd, 1H, Ar), 8.23 (d, 1H, Ar), 11.29 (br s, 1H, N). ¹³C NMR (500 MHz, CDCl₃) δ = 13.71 (CH₃), 22.54, 29.95, 31.82, 36.34 (4CH₂), 42.60 (CH₃), 44.88 (CH₂), 55.86 (CH₃), 94.13, 111.38, 112.12, 113.95, 120.79, 125.51, 126.51 (7CH), 129.37, 130.72, 137.25, 147.87, 148.98, 153.87, 169.25, 190.15 (8C). MS (GC, 70 eV): m/z (%) = 447 (M⁺, 31), 411 (58), 231 (16).

(Z)-1-(2-Chloro-5-nitrophenyl)-3-(cyclohexylamino)hept-2-en-1-one (10b). Brown oil, yield 12%. ¹H NMR (500 MHz, CDCl₃) δ = 0.95 (t, ³J = 7.3 Hz, 3H, CH₃), 1.37–1.47 (m, 6H, cyclohexyl), 1.56–1.63 (m, 3H, cyclohexyl), 1.81–1.84 (m, 2H, –CH₂CH₂CH₂–), 1.92–1.94 (m, 2H, –CH₂CH₂CH₂–), 2.30–2.33 (m, 2H, –CH₂CH₂CH₂–), 3.47–3.53 (m, 1H, cyclohexyl), 5.23 (s, 1H, –CH=C), 7.51 (d, ³J = 8.7 Hz, 1H, Ar), 8.08 (dd, ³J = 8.7 Hz, ⁴J = 2.8 Hz, 1H, Ar), 8.33 (d, ⁴J = 2.7 Hz, 1H, Ar), 11.45 (d, J = 8.1 Hz, 1H, NH). ¹³C NMR (500 MHz, CDCl₃) δ = 13.79 (CH₃), 22.61, 24.48, 25.21, 30.62, 31.73, 33.96 (8CH₂), 51.95, 94.32, 123.94, 124.49, 131.05 (5CH), 137.85, 142.82, 146.34, 169.08, 184.68. IR (ATR): [small nu, Greek, tilde] = 2928 (w), 2854 (w), 1591 (s), 1573 (s), 1519 (s), 1451 (w), 1401 (w), 1336 (s), 1247 (m), 1189 (w), 1151 (w), 1122 (m), 1097 (m), 1040 (m), 917 (w), 890 (w), 866 (w), 831 (m), 739 (s), 650 (w), 578 (w), 532 (w). MS (GS): m/z (%) = 366 (M⁺, C₁₉H₂₅O₃N₂³⁷Cl, 10), 364 (M⁺, C₁₉H₂₅O₃N₂³⁵Cl, 29), 335 (12), 322 (24), 307 (13), 294 (23), 287 (26), 283 (25), 253 (14), 243 (34), 241 (100), 215 (12), 213 (36), 186 (25), 184 (76), 180 (39), 139 (10), 138 (48), 126 (10), 124 (23), 83 (11), 82 (15), 81 (11), 67 (16), 55 (50), 41 (37). HRMS (ESI): calcd for C₁₉H₂₅O₃N₂³⁵Cl: 364.1548, found: 364.1544; C₁₉H₂₅O₃N₂³⁷Cl: 366.1518, found: 366.1521.

General procedure for the synthesis of 11

Under a constant flow of an inert gas a pressure tube was charged with a magnetic stirrer, 6a (450 mg, 1 equiv.), K₃PO₄ (2 equiv.), extra dry dimethylformamide (6 mL) and methylaniline (1.7 equiv.). After stirring for 8 h at 120 °C the solvent was evaporated under reduced pressure. Residue was purified by a column chromatography (silica gel, heptane/ethyl acetate, 25 : 1).

(Z)-1-(2-Chloro-5-nitrophenyl)-3-(methyl(phenyl)amino)-3-p-tolylprop-2-en-1-one (11). Brown powder, yield 58%. Mp 118–120 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 2.08 (s, 3H, –NPhCH₃), 3.37 (s, 3H, –CH₃, –Tol), 5.61 (s, 1H, –COCH=), 6.81 (d, 2H, ³J = 7.9 Hz, –Tol), 7.05 (d, 2H, ³J = 7.9 Hz, –Tol), 7.13–7.33 (m, 5H, Ph), 7.48 (d, 1H, ³J = 8.8 Hz, Ar), 7.73 (d, 1H, ⁴J = 2.8 Hz, Ar), 7.96 (dd, 1H, ³J = 8.8 Hz, ⁴J = 2.8 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 20.53, 42.40 (2CH₃), 103.37, 123.33, 123.44, 126.43 (4CH), 127.12, 128.05, 129.18, 129.57 (8CH), 130.65 (CH), 131.67, 136.30, 138.33, 142.69, 145.34, 145.67, 164.28, 187.40 (8C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2920 (m), 1597 (m), 1488 (s), 1390 (m), 1340 (s), 1272 (m), 1093 (m), 1032 (m), 898 (m), 819 (m), 739 (s), 696 (s). MS (GC, 70 eV): m/z (%) = 406 (M⁺, 27), 391 (18), 390 (13), 389 (43), 250 (31), 223 (14), 222 (87), 221 (10), 207 (35), 194 (11), 184 (11), 138 (14), 133 (10), 132 (100), 115 (12), 110 (12), 106 (11), 91 (11), 77 (18). HRMS (EIHR): calcd for C₂₃H₁₉N₂O₃: 406.1078, found: 406.1084.

General procedure for the synthesis of 12

Under a constant flow of an inert gas a pressure tube was charged with a magnetic stirrer, 1-(2-chloro-5-nitrophenyl)-3-p-tolylprop-2-yn-1-one 6a (500 mg, 1 equiv.), K₂CO₃ (462 mg, 2 equiv.), extra dry dimethylformamide (9 mL) and diaminobutane (for 12a) or diaminohexane (for 12b) (0.51 equiv.). After stirring for 8 h at 120 °C the solvent was evaporated. Residue was recrystallized from toluene.

1,1′-(Butane-1,4-diyl)bis(6-nitro-2-p-tolylquinolin-4(1H)-one) (12a). Yellow crystals, yield 75%. Mp 370–372 °C. ¹H NMR (250.13 MHz DMSO-d₆): δ = 1.55 (br s, 4H, –CH₂–(CH₂)₂–CH₂–), 2.22 (s, 6H, –CH₃, –Tol), 4.25 (br s, 4H, =NCH₂(CH₂)₂CH₂N=), 6.98 (s, 2H, 2COCH=), 7.05 (d, 4H, ³J = 8.0 Hz, –Tol, –Tol′), 7.16 (d, 4H, ³J = 8.0 Hz, –Tol, –Tol′), 7.98 (d, 2H, ³J = 9.7 Hz, Ar, Ar′), 8.54 (dd, 2H, ³J = 9.7 Hz, ⁴J = 2.4 Hz, Ar, Ar′), 9.12 (d, 2H, ⁴J = 2.4 Hz, Ar, Ar′). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 23.00 (2CH₃, –Tol, Tol′), 28.31, 53.17 (4CH₂), 113.21, 123.19 (4CH), 124.23 (2C), 124.46 (2CH), 130.20, 131.59 (4CH), 132.69 (2C), 132.84 (2CH), 145.19, 145.49, 148.63, 166.11, 173.26 (10C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2919 (s), 1631 (s), 1470 (s), 1334 (s), 1171 (m), 1112 (m), 910 (m), 823 (s), 749 (s), 651 (m), 538 (m). HRMS (ESI-TOF): calcd for C₃₆H₃₀N₄O₆: 614.2159, found: 614.2165.

1,1′-(Hexane-1,6-diyl)bis(6-nitro-2-p-tolylquinolin-4(1H)-one) (12b). Yellow-green crystals, yield 92%. Mp 333–335 °C. ¹H NMR (300.13 MHz DMSO-d₆): δ = 0.84 (br s, 4H, =N–(CH₂)₂(CH₂)₂(CH₂)₂–N=), 1.53 (br s, 4H, =N–CH₂CH₂(CH₂)₂CH₂CH₂–N=), 2.23 (s, 6H, Tol–CH₃), 4.34 (t, 4H, ³J = 7.6 Hz, =N–CH₂(CH₂)₄CH₂–N=), 7.03 (s, 2H, 2COCH=), 7.17 (d, 4H, ³J = 8.3 Hz, –Tol, –Tol′), 7.21 (d, 4H, ³J = 8.3 Hz, –Tol, –Tol′), 8.06 (d, 2H, ³J = 9.7 Hz, Ar, Ar′), 8.58 (dd, 2H, ³J = 9.7 Hz, ⁴J = 2.6 Hz, Ar, Ar′), 9.14 (d, 2H, ⁴J = 2.6 Hz, Ar, Ar′). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 22.75 (2CH₃), 27.59, 31.23, 53.92 (6CH₂), 112.79, 123.17, 124.07 (6CH), 124.44 (2C), 130.13 (4CH), 131.11 (2CH), 132.44 (4CH), 132.77, 144.90, 145.03, 148.26, 165.70, 172.97 (12C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 3057 (w), 2936 (w), 1640 (s), 1469 (s), 1330 (s), 1113 (m), 1057 (m), 910 (m), 832 (m), 745 (m), 653 (w). 528 (m). MS (GC, 70 eV): m/z (%) = 642 (M⁺, 5), 204 (22), 177 (51), 163 (14), 162 (100), 152 (13), 148 (11), 146 (15), 137 (22), 136 (18), 135 (13), 134 (18), 123 (11), 121 (26), 120 (23), 119 (40), 117 (13), 115 (10), 107 (10), 105 (18), 91 (30), 79 (11), 77 (25), 71 (10), 69 (15), 67 (11), 66 (56), 65 (33), 57 (16), 55 (15), 44 (100), 43 (37), 41 (22), 40 (12), 39 (24). HRMS (ESI): calcd for C₃₈H₃₄N₄O₆: 642.2472, found: 642.2478.

General procedure for the synthesis of 13

Under a constant flow of an inert gas a pressure tube was charged with magnetic stirrer, 1-(2-chloro-5-nitrophenyl)-3-p-tolylprop-2-yn-1-one 6a (250 mg, 1 equiv.), K₃PO₄ (354 mg, 2 equiv.), extra dry dimethylformamide (4 mL) and 6-amino-1-n-propyl-2-p-tolyl-4-quinolone 8ai (for 13a) or 6-amino-1-isopropyl-2-p-tolylquinolin-4(1H)-one 8aj (for 13b) (0.91 equiv.) under inert gas flow. After stirring for 8 h at 120 °C the solvent was evaporated. Residue was purified by a column chromatography (silica gel, heptane/ethyl acetate, 6 : 1 to 1 : 1).

6-Nitro-1′-propyl-2,2′-di-p-tolyl-4H-1,6′-biquinoline-4,4′(1′H)-dione (13a). Brown crystals, yield 11%. Mp 350–352 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 0.91–5.00 (m, 13H, Alk), 5.91 (s, 1H, –COCH=), 8.39–8.90 (m, 9H, Ar), 9.44 (s, 1H, Ar), 9.66 (s, 1H, Ar), 9.97 (s, 1H, Ar), 10.79 (s, 1H, Ar), 14.27 (CF₃COOD). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 10.81, 21.56, 21.77 (3CH₃), 24.43, 55.37 (2CH₂), 112.01, 112.08, 123.19, 123.23 (4CH), 123.60 (2CH), 126.30 (C), 128.01 (CH), 129.19, 130.75 (4CH), 130.92 (CH), 131.42 (2CH), 131.53 (C), 131.85 (2CH), 136.48, 138.34, 142.24 (3C), 144.85, 144.86 (4C), 146.18, 148.08, 165.96, 169.66, 173.43 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 1638 (s), 1601 (s), 1469 (s), 1337 (s), 1176 (m), 1063 (m), 822 (s), 745 (m), 582 (m). MS (GC, 70 eV): m/z (%) = 556 (M⁺¹, 39), 555 (M⁺, 100), 554 (M⁻¹, 38), 526 (11). HRMS (EIHR): calcd for C₃₅H₂₉N₃O₄: 555.2153, found: 555.2136.

1′-Isopropyl-6-nitro-2,2′-di-p-tolyl-4H-1,6′-biquinoline-4,4′(1′H)-dione (13b). Pale brown crystals, yield 19%. Mp 325–327 °C. ¹H NMR (250.13 MHz, DMSO-d₆): δ = 1.49 (d, 3H, ³J = 7.1 Hz, CH₃, i-Pr), 1.60 (d, 3H, ³J = 7.1 Hz, CH₃, i-Pr), 2.23 (s, 3H, CH₃, –Tol), 2.43 (s, 3H, CH₃, –Tol), 4.63 (m, 1H, i-Pr), 5.93 (s, 1H, –COH=), 6.32 (s, 1H, –COH=), 7.06 (d, 1H, ³J = 9.5 Hz, Ar), 7.11 (d, 2H, ³J = 8.2 Hz, –Tol), 7.33 (d, 2H, ³J = 7.9 Hz, –Tol), 7.40 (d, 2H, ³J = 8.2 Hz, –Tol), 7.47 (d, 2H, ³J = 7.9 Hz, –Tol), 7.86 (dd, 1H, ³J = 9.2 Hz, ⁴J = 2.6 Hz, Ar′), 8.13 (d, 1H, ³J = 9.2 Hz, Ar′), 8.25 (d, 1H, ⁴J = 2.6 Hz, Ar′), 8.38 (dd, 1H, ³J = 9.5 Hz, ⁴J = 2.8 Hz, Ar), 9.02 (d, 1H, ⁴J = 2.8 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 20.28 (CH₃), 20.68 (2CH₃), 20.85 (CH₃), 53.92 (CH), 112.39, 112.90, 120.26, 121.23, 121.45 (5CH), 124.99 (C), 126.26, 127.13 (2CH), 127.63 (2CH), 128.16 (C), 128.52, 129.07, 129.45 (6CH), 131.98 (C), 132.47 (CH), 133.52, 133.73, 138.54, 139.19, 139.76, 142.86, 146.08, 155.35, 156.16, 174.60, 175.59 (11C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2922 (w), 1639 (s), 1602 (s), 1509 (m), 1469 (s), 1376 (m), 1335 (s), 1166 (m), 1063 (m), 823 (s), 746 (m), 533 (w). MS (EI, 70 eV): m/z (%) = 556 (M⁺¹, 30), 555 (M⁺, 100), 514 (18), 513 (69), 512 (67), 482 (10), 467 (11), 466 (21), 44 (22). HRMS (EIHR): calcd for C₃₅H₂₉N₃O₄: 555.2153, found: 555.2145.

General procedure for the synthesis of 14

Preliminarily the 6-amino-4-quinolone 8b (0.2 g, 1 equiv.) was dissolved in 2 mL of acetonitrile. Under the flow of argon a three-necked round-bottom flask equipped with a reflux condenser and a bubble counter was charged with a magnetic stirrer, CuBr₂ (1.2 equiv., 145 mg), t-BuNO₂ (1.5 equiv., 0.1 mL) and 2 mL of acetonitrile. After that it was closed with a septum stopper and stirred for 15 min. After 15 min the solution of 8b was injected to the flask. The stirring was held overnight at room temperature. For product isolation the acetonitrile was evaporated under the reduced pressure and purified by the column chromatography (eluent heptane : ethylacetate 4 : 1; R_f ≈ 0.5). The by-product is 6-bromo-4-quinolone, yield 17%, R_f ≈ 0.25.

3,6-Dibromo-1-(4-methoxybenzyl)-2-p-tolylquinolin-4(1H)-one (14). Wight crystals, yield 72%. Mp 185–186 °C. ¹H NMR (250.13 MHz, DMSO-d₆): δ = 2.38 (s, 3H, –CH₃, –Tol), 3.71 (s, 3H, –OCH₃), 5.28 (s, 2H, –CH₂–), 6.86 (d, 2H, ³J = 8.8 Hz, Ar′), 7.00 (d, 2H, ³J = 8.8 Hz, Ar′), 7.34 (s, 4H, –Tol), 7.56 (d, 1H, ³J = 9.3 Hz, Ar), 7.84 (dd, 1H, ³J = 9.3 Hz, ⁴J = 2.5 Hz, Ar), 8.41 (d, 1H, ⁴J = 2.5 Hz, Ar). ¹³C NMR (250.13 MHz, DMSO-d₆): δ = 20.88 (CH₃), 52.59 (CH₂), 54.97 (CH₃), 108.93 (C), 114.16 (2CH), 117.14 (C), 121.09 (CH), 125.92 (C), 126.74 (2CH), 127.49 (C), 127.69 (2CH), 128.05 (CH), 129.48 (2CH), 132.53 (C), 135.11 (CH), 138.50, 139.38, 153.82, 158.41, 169.96 (5C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2919 (w), 1610 (s), (1588 (s), 1504 (s), 1454 (s), 1247 (s), 1175 (s), 1098 (m), 1029 (m), 888 (m), 804 (s), 748 (m), 657 (m), 536 (m). MS (GC, 70 eV): m/z (%) = 513 (M⁺, 5), 122 (26), 121 (100), 78 (10). HRMS (ESI): calcd for C₂₄H₁₉⁸⁰Br₂NO₂: 510.9777, found: 510.9759; calcd for C₂₄H₁₉⁸⁰Br⁸¹Br NO₂: 512.9757, found: 512.9749; calcd for C₂₄H₁₉⁸¹Br₂NO₂: 514.9736, found: 514.9737.

General procedure for the synthesis of 15

A two-necked round bottom flask, where one neck was equipped with an airproof water condenser, was charged with a magnetic stirrer, 14 (1 equiv., 200 mg), appropriate boronic acid (2.4 equiv.), tetrakis(triphenylphosphine)palladium(0) (0.2 equiv., 96 mg) and closed with a rubber septa. This mixture was threefold vacuumized and filled with argon and afterwards 11 mL of toluene were injected to the flask through the rubber septa. K₂CO₃ (20 equiv., 1154 mg) dissolved in a mixture of H₂O (2 mL) and MeOH (3 mL) was injected to the flask. After that the reaction was stirred under an inert atmosphere at 90 °C for 4 hours. The product was purified by column chromatography (silica gel, heptanes–ethyl acetate eluent).

3,6-Bis(4-ethylphenyl)-1-(4-methoxybenzyl)-2-p-tolylquinolin-4(1H)-one (15). Pale yellow crystals, yield 10%. Mp 232–234 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 1.15 (t, 3H, ³J = 7.5 Hz, –CH₂–CH₃), 1.24 (t, 3H, ³J = 7.5 Hz, –CH₂–CH₃), 2.22 (s, 3H, –Tol), 2.50 (1/2 q, 2H + DMSO-d₆, ³J = 7.5 Hz, –CH₂–CH₃), 2.68 (q, 2H, ³J = 7.5 Hz, –CH₂–CH₃), 5.244 (s, 2H, –CH₂–, Ar′), 6.89 (d, 2H, ³J = 8.7 Hz, Ar), 6.95–7.10 (m, 8H, Ar), 7.19 (d, 2H, ³J = 7.8 Hz, Ar), 7.36 (d, 2H, ³J = 7.8 Hz, Ar), 7.64 (d, 1H, ³J = 9.1 Hz, Ar), 7.68 (d, 2H, ³J = 8.1 Hz, Ar), 7.97 (dd, 1H, ³J = 9.1 Hz, ⁴J = 2.3 Hz, Ar), 8.54 (d, 1H, ⁴J = 2.3 Hz, Ar). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 15.34, 15.52, 20.72 (3CH₃), 27.74, 27.78 (2CH₂), 51.06 (CH₂), 54.97 (CH₃), 114.15 (2CH), 118.96, 122.82 (2CH), 123.60 (C), 126.48 (4CH), 126.82, 128.52 (4CH), 128.57 (C), 128.59, 128.99 (4CH), 130.40 (CH), 131.29 (2CH), 131.59, 133, 69, 134.99, 136.29, 137.93, 139.32, 140.88, 143.27, 152, 30 (8C), 158.30 (2C), 175.09 (C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2924 (w), 1591 (s), 1505 (s), 1479 (m), 1454 (m), 1327 (w), 1288 (m), 1244 (s), 1174 (m), 1113 (m), 1032 (m), 907 (m), 811 (m), 747 (m), 657 (m), 534 (m). MS (GC, 70 eV): m/z (%) = 564 (M⁺¹, 12), 563 (M⁺, 32), 540 (25), 539 (72), 538 (25), 537 (70), 459 (11), 458 (11), 443 (29), 442 (64), 441 (11), 419 (19), 417 (19), 339 (11), 338 (11), 337 (11), 322 (20), 122 (77), 121 (100), 91 (12), 77 (13). HRMS (ESI-TOF): calcd for C₄₀H₃₇NO₂: 563.2818, found: 563.2824.

General procedure for the synthesis of 16

Compound 16 was synthesized analogously to 15.

3,6-Bis(4-ethylphenyl)-4H-chromen-4-one (16). White crystals, yield 48%. Mp 135–137 °C. ¹H NMR (300.13 MHz, DMSO-d₆): δ = 1.25 (dt, 6H, ³J = 7.6 Hz, 2CH₃–CH₂–C₄H₄–), 2.69 (dq, 4H, ³J = 7.6 Hz, 2CH₃–CH₂–C₄H₄–), 7.31 (d, 2H, ³J = 8.2 Hz, Ar′), 7.37 (d, 2H, ³J = 8.2 Hz, Ar′), 7.56 (d, 2H, ³J = 8.2 Hz, Ar′), 7.69 (d, 2H, ³J = 8.2 Hz, Ar′), 7.77 (d, 1H, ³J = 8.8 Hz, Ar), 8.12 (dd, 1H, ³J = 8.8 Hz, ⁴J = 2.3 Hz, Ar), 8.33 (d, 1H, ⁴J = 2.3 Hz, Ar), 8.55 (s, 1H, –CH=). ¹³C NMR (300.13 MHz, DMSO-d₆): δ = 15.44, 15.58 (2CH₃), 27.75, 27.92 (2CH₂), 119.03, 122.29 (2CH), 123.79, 123.98 (2C), 126.73, 127.55, 128.51, 128.81 (8CH), 129.12 (C), 132.36 (CH), 135.89, 137.31, 143.53, 143.60 (4C), 154.25 (CH), 154.88, 175.13 (2C). IR (ATR, cm⁻¹): [small nu, Greek, tilde] = 2961 (w), 1640 (s), 1610 (s), 1475 (s), 1329 (m), 1267 (s), 1229 (m), 1186 (m), 1115 (m), 1048 (m), 899 (m), 816 (s), 666 (m), 551 (m). MS (GC, 70 eV): m/z (%) = 354 (M⁺, 100), 339 (45), 162 (11), 115 (18). HRMS (ESI): calcd for C₂₅H₂₂O₂: 354.1614, found: 354.1620.

Acknowledgements

Financial support by the State of Mecklenburg-Vorpommern and by the DAAD (program Zusammenarbeit deutscher und pakistanischer Hochschulen) is gratefully acknowledged. J. Iqbal is thankful to the Organization for the Prohibition of Chemical Weapons (OPCW), The Hague, The Netherlands and Higher Education Commission of Pakistan for the financial support through Project No. 20-3733/NRPU/R&D/14/520.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1403824, 934415–934417 and 934420. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra10948e

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