Synthesis of bicyclic 2-pyridones by regioselective annulations of heterocyclic ketene aminals with anhydrides

Abstract

An efficient strategy for the synthesis of substituted bicyclic 2-pyridones is developed. The proposed approach is based on the regioselective N-acylation of heterocyclic ketene aminals (HKAs) with methacrylic anhydride or crotonic anhydride. The tolerance of the developed methodology allows for the construction of fused 2-pyridone ring systems in excellent yields with a variety of functional groups HKAs as synthons under neutral conditions.

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Introduction

2-Pyridones are important heterocyclic ring systems that serve as key core scaffolds in a large quantity of natural products and biologically active molecules.¹ Among the 2-pyridone derivatives, substituted bicyclic 2-pyridones are known to act as inhibitors of pilus formation² and functional amyloids (Fig. 1, FN075)³ in Uropathogenic Escherichia coli (UPEC). Other representative ring-fused 2-pyridones are reported as Chlamydia trachomatis inhibitors,⁴ acetylcholinesterase inhibitors (Fig. 1, A58365B),⁵ PARP-1 inhibitors (Fig. 1, PJ34)⁶ and amyloid-β peptide aggregation inhibitors.⁷

Fig. 1 Biologically active bicyclic 2-pyridones.

Owing to the synthetic utilisation and biological significance of substituted bicyclic 2-pyridones, various synthetic methods have been developed to prepare these scaffolds. These methods include cyclocondensation of ketenaminals,⁸ addition of diamines to cyanobutenoic esters,⁹ addition of diamines to 1-halo or methylthiopyridones,¹⁰ nucleophilic substitution and intramolecular condensation of 2,6-dihalopyridine¹¹ and so on.¹² The first method is the most used procedure. Heterocyclic ketene aminals (HKAs), as special ketene aminals, are of particular interest as they have been proven to be effective building blocks for constructing various fused heterocyclic systems in the past few decades.^13–17

Substituted bicyclic 2-pyridone ring systems can be obtained from the reaction of HKAs with a number of bis-electrophilic reagents, including α,β-unsaturated carboxylic acid derivatives,¹⁸ Meldrum's acid,¹⁹ aryl aldehydes,¹⁹ itaconic anhydride²⁰ and propiolic acid esters.²¹ Nevertheless, these reported methodologies all suggest that the annulation proceeds via initial conjugate C-addition, followed by cyclocondensation to form the target products (e.g., β-ketoester enol tosylates, Scheme 1). To our knowledge, the N-acylation of HKAs has scarcely been studied during the past decade.^13a On the basis of these consideration, we herein report the first example of the efficient synthesis of bicyclic 2-pyridones via a regioselective N-acylation, followed by an intramolecular annulation strategy (Scheme 1).

Scheme 1 Different mechanism of formation bicyclic 2-pyridones.

Results and discussion

To date, only propionyl chloride and ethyl formate have been used as acylation agents to study the N-acylation reaction of HKAs. Reactions between HKAs and propionyl chloride proceed quickly at room temperature, but with poor regioselectivity²² (Fig. 2). In order to improve the regioselectivity of the N-acylation reaction, the Huang group used ethyl formate as an acylation agent to increase the proportion of N-acylated products, while avoiding the formation of C-acylated products (Fig. 2).²³ However, the reaction requires a strong basic medium (NaH) and tedious work-up procedures. We commenced our studies by exploring the acylation of HKAs with acetic anhydride. Five-membered HKAs 1i was reacted with acetic anhydride in acetonitrile in the presence of Et₃N under refluxing for 20 min. Unexpected, the reaction proceeded efficiently to give the N-acetylated compound 3 as the sole product in high yield (94%, Fig. 2). To the best of our knowledge, the N-acylation of HKAs with acid anhydride has not yet been featured in the literature, therefore, our success in the regiospecific N-acetylation reaction of HKAs led us to attempt the synthesis of bicyclic 2-pyridone compounds from the reaction with α,β-unsaturated acid anhydride.

Fig. 2 The acylation of heterocyclic ketene aminals (HKAs).

The reaction between HKA 1a (1.0 equiv.) and the easily available material methacrylic anhydride (2a, 1.2 equiv.) was chosen as a model reaction for the optimisation of reaction conditions. Firstly, we performed the reaction in the presence of basic catalysts or without catalysts in acetonitrile at room temperature for 60 min. The results showed that the reactions could proceed in neutral conditions at room temperature, while the organic base Et₃N did not obviously promote the reactions (Table 1, entries 1–2). Subsequently, we screened several aprotic and protonic solvents in neutral conditions at room temperature (Table 1, entries 3–7). The results revealed that the most suitable solvent for this transformation was anhydrous 1,4-dioxane. Obviously, the polarity of the solvents had a certain influence on the rate of the reaction. Therefore, we propose that the optimum reaction conditions are anhydrous 1,4-dioxane as the solvent with no catalyst at room temperature for 40 min (Table 1, entry 7).

Table 1 Optimization of reaction conditions^a

Entry	Solvent^b	Base	Time/min	Yield^d (%)
a Reagents and conditions: HKA 1a (1.0 mmol) was dissolved in anhydrous solvent (10.0 mL), methacrylic anhydride 2a (1.2 mmol) was added dropwise to the solution at room temperature.b Anhydrous solvent.c Et3N (10 mmol%).d Isolated yield based on HKA 1a.
1	CH3CN	Et3N^c	60	87
2	CH3CN	—	60	85
3	Toluene	—	120	72
4	CH2Cl2	—	120	77
5	EtOH	—	30	78
6	MeOH	—	20	73
7	1,4-Dioxane	—	40	92

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Based on the optimised reaction conditions, the scope and limitations of this protocol were examined, and six-membered ring HKAs (4b–4e) were used as substrates to react with methacrylic anhydride 2a. As can be seen, the six-membered ring HKAs with different carbonyl-substituent groups, were all good substrates for the cyclisation reaction at room temperature and gave the corresponding bicyclic 2-pyridones 4a–4e. A variety of substituents on the HKA phenyl rings also had a slight influence on the reactivity and product yield (Table 2, entries 1–4). When the nitro-substituted HKA (1n) was used as a substrate for the cyclisation under the same conditions, the target product could be obtained with a 95% yield when the time of the reaction was prolonged to 300 min (Table 2, entry 5). Subsequently, the ring size of the cycles in the HKAs was also investigated. The five- and seven-membered ring HKAs were reacted with methacrylic anhydride 2a. The reactions proceeded smoothly under the same conditions and the final products were achieved with moderate to good yields (Table 2, entries 6–14). It was noticeable that varying the ring size of the cycles in the HKAs had an obvious effect on reaction time. Generally, five-membered HKAs as substrates needed more reaction time than six- and seven-membered HKAs in the cyclisation reaction. Additionally, it was found that five- and six-membered HKAs often gave higher yields than those of seven-membered ones.

Table 2 Preparation of bicyclic pyridone derivatives^a

Entry	n	EWG	4	Time/min	Yield^b (%)
a Reagents and conditions: HKA 1 (1.0 mmol) was dissolved in anhydrous dioxane (10.0 mL), methacrylic anhydride 2a (1.2 mmol) was added dropwise to the solution at room temperature.b Isolated yield based on HKA 1.
1	2	p-MeC6H4CO (1a)	4a	40	92
2	2	p-MeOC6H4CO (1b)	4b	20	91
3	2	p-ClC6H4CO (1c)	4c	30	92
4	2	p-FC6H4CO (1d)	4d	30	91
5	2	NO2 (1e)	4e	300	95
6	3	p-MeOC6H4CO (1f)	4f	20	83
7	3	C6H4CO (1g)	4g	30	86
8	1	p-MeC6H4CO (1h)	4h	90	92
9	1	C6H4CO (1i)	4i	90	89
10	1	p-MeOC6H4CO (1j)	4j	60	94
11	1	p-ClC6H4CO (1k)	4k	90	93
12	1	o-ClC6H4CO (1l)	4l	90	90
13	1	p-FC6H4CO (1m)	4m	90	89
14	1	NO2 (1n)	4n	360	91

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In an endeavour to expand the scope of substrates 2, crotonic anhydride 2b was reacted with five-, six- and seven-membered HKAs with different substituent groups to give the corresponding bicyclic 2-pyridones 5. Compared to 2a, the reaction can also provide the target compounds with good yields, but the reaction time needs to be prolonged (Table 3).

Table 3 Preparation of bicyclic pyridone derivatives^a

Entry	n	EWG	5	Time/min	Yield^b (%)
a Reagents and conditions: HKA 1 (1.0 mmol) was dissolved in anhydrous dioxane (10.0 mL), crotonic anhydride 2b (1.2 mmol) was added dropwise to the solution at room temperature.b Isolated yield based on HKA 1.
1	2	p-MeOC6H4CO (1b)	5a	90	91
2	2	C6H4CO (1q)	5b	90	87
3	2	p-ClC6H4CO (1c)	5c	90	92
4	2	p-FC6H4CO (1d)	5d	90	87
5	2	NO2 (1e)	5e	420	96
6	3	p-MeOC6H4CO (1f)	5f	60	87
7	3	C6H4CO (1g)	5g	90	86
8	1	p-MeC6H4CO (1h)	5h	120	93
9	1	C6H4CO (1i)	5i	120	91
10	1	p-ClC6H4CO (1k)	5j	120	94
11	1	o-ClC6H4CO (1l)	5k	120	92
12	1	p-FC6H4CO (1m)	5l	120	90

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The Huang group found that benzoyl chloride as an acylation agent reacts with N-methyl HKAs in acetonitrile solution at room temperature to get complex compounds²⁴ including N-, C- and O-benzoylation products. In order to further investigate the scope of HKAs in this protocol, N-substituent HKAs 1o and 1p were also employed to react with α,β-unsaturated anhydrides 2 in refluxing 1,4-dioxane to give the corresponding N-benzyl bicyclic 2-pyridones 6 with good yield. However, it is worth noting that the reactivity of N-benzyl HKAs is much lower than HKAs in the cyclisation reaction (Table 4).

Table 4 Preparation of bicyclic pyridone derivatives^a

Entry	R	R′	R^2	6	Time/h	Yield^b (%)
a Reagents and conditions: HKA 1 (1.0 mmol) was dissolved in anhydrous dioxane (10.0 mL), methacrylic anhydride 2a or crotonic anhydride 2b (1.2 mmol) was added dropwise to the solution at reflux temperature.b Isolated yield based on HKA 1.
1	H	Me	F	6a	3	92
2	H	Me	CN	6b	8	87
3	Me	H	F	6c	4	93
4	Me	H	CN	6d	8	90

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The ¹H and ¹³C NMR spectra, IR spectra and high resolution mass spectra data confirmed the structure of the target compounds 4–6. In order to specifically test the structure, 4j was characterised by X-ray crystallography as a representative compound, as shown in Fig. 3.

Fig. 3 ORTEP diagram of 4j; ellipsoids are drawn at the 30% probability level.

Depending on the above results of the N-acetylation of the HKAs, a proposed mechanism for the synthesis of bicyclic pyridones 4–6 is shown in Scheme 2. Apparently, HKA 1 reacted via N-acylation with unsaturated anhydride 2 to give intermediate 7, followed by a rapid annulation reaction by an intramolecular Michael addition to form 8. Compound 8 is followed by imine-enamine tautomerisation to give intermediate 9. Finally, intermediate 9 was used to obtain target compounds 4–6 by keto-enol tautomerisation.

Scheme 2 Proposed mechanism for regioselective synthesis of substituted bicyclic 2-pyridones.

Conclusions

We have successfully developed an efficient method for the construction of a series of novel bicyclic pyridone derivatives 4–6 by regioselective acylations and intramolecular annulations of HKAs with methacrylic anhydride or crotonic anhydride under neutral conditions. The tolerance of this methodology to a variety of HKA functional groups is a great advantage in the synthesis of fused 2-pyridone ring systems. The features of this strategy include some important aspects like excellent yields, convenient operation and mild synthesis conditions.

Experimental

General information

All compounds were fully characterised by spectroscopic data. The NMR spectra were recorded on a Bruker Ascend III 600 or DRX500 (¹H: 600 or 500 MHz, ¹³C: 150 or 125 MHz). Chemical shifts (δ) are expressed in ppm and J values are given in Hz. Deuterated CDCl₃ and DMSO-d₆ were used as solvents. IR spectra were recorded on a FT-IR Thermo Nicolet Avatar 360 using a KBr pellet. The reactions were monitored by thin layer chromatography (TLC) using silica gel GF254. The melting points were determined on a XT-4A melting point apparatus and are uncorrected. HRMs were performed on an Agilent LC/Msd TOF instrument. Unless otherwise stated, all regents used are commercially available. Solvents for reactions were purified by standard procedures. Compounds 1a–1n were prepared according to the literature.²⁵ Materials 1o and 1p were synthesised according to the literature.²⁶

Typical procedure for the synthesis of bicyclic 2-pyridones 4 and 5

HKA derivative 1 (1.0 mmol) was added to a 25 mL round-bottom flask and dissolved in dry dioxane (10.0 mL). Methacrylic anhydride 2a or crotonic anhydride 2b (1.2 mmol) was added under stirring at room temperature, the mixture was stirred until TLC revealed that the conversion of the starting material was complete at about 0.5–6 h. A small amount of H₂O (ca. 10 mL) was added and the mixture was extracted with EtOAc (25 mL × 3). The combined organic extracts were dried over anhydrous Na₂SO₄ and evaporated in vacuo. The crude residue was dried and recrystallised from petroleum ether–EtOAc to afford the pure products 4 and 5 with a yield of 83–96%.

Typical procedure for the preparation of compounds 6

HKA derivatives 1o and 1p (1.0 mmol), methacrylic anhydride 2a or crotonic anhydride 2b (1.2 mmol) and dry dioxane (10.0 mL) were placed in a 25 mL round-bottom flask and the mixture was stirred at reflux for 3–8 h. Completion was monitored by TLC. Then, the reaction mixture was cooled to room temperature and filtered to give the pure crude product, which was further washed with petroleum ether–EtOAc (1 : 1) to give pure product 6 with a yield of 87–93%.

2-(1-Acetylimidazolidin-2-ylidene)-1-(p-tolyl)ethan-1-one (3). White solid: mp 207–208 °C; IR (KBr): 3449, 3168, 2091, 1691, 1604, 1496, 1391, 1310, 1256, 767 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆): δ = 10.21 (br, 1H, NH), 7.68 (d, J = 8.0 Hz, 2H, PhH), 7.25 (d, J = 7.9 Hz, 2H, PhH), 6.86 (s, 1H, C=CH), 4.03–3.63 (m, 4H, NCH₂CH₂), 2.34 (s, 3H, CH₃), 2.24 (s, 3H, CH₃); ¹³C NMR (125 MHz, DMSO-d₆): δ = 186.6, 170.2, 158.6, 140.7, 138.1, 129.2, 126.9, 79.0, 45.8, 42.0, 25.5, 21.3; HRMS (ESI) m/z calcd for C₁₄H₁₇N₂O₂ [M + H]⁺, 245.1285; found, 245.1284.

7-Methyl-9-(4-methylbenzoyl)-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyrimidin-6-one (4a). White solid: mp 157–158 °C; IR (KBr): 3423, 2967, 2815, 1695, 1605, 1575, 1241, 1155, 746 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 12.62 (br, 1H, NH), 7.23–7.22 (m, 2H, PhH), 7.19–7.17 (m, 2H, PhH), 3.84–3.56 (m, 2H, NCH₂), 3.44–3.36 (m, 2H, NCH₂), 3.48–3.44 (m, 2H, CH₂), 2.32 (s, 3H, CH₃), 2.31–2.26 (m, H, CH), 1.95–1.88 (m, 2H, CH₂), 1.03–1.02 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 187.3, 173.2, 156.5, 140.0, 138.3, 128.8, 127.2, 86.6, 39.6, 38.4, 30.0, 21.3, 20.7, 15.6; HRMS (ESI) m/z calcd for C₁₇H₂₁N₂O₂ [M + H]⁺, 285.1598; found, 285.1598.

9-(4-Methoxybenzoyl)-7-methyl-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyrimidin-6-one (4b). White solid: mp 178–179 °C; IR (KBr): 3553, 3415, 2968, 1686, 1601, 1451, 1274, 1153, 837, 603 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 12.63 (br, 1H, NH), 7.31 (d, J = 8.6 Hz, 2H, PhH), 6.93 (d, J = 8.6 Hz, 2H, PhH), 3.85–3.57 (m, 2H, NCH₂), 3.78 (s, 3H, OCH₃), 3.42–3.33 (m, 2H, NCH₂), 2.51–2.50 (m, H, CH), 2.49–2.36 (m, 2H, CH₂), 1.94–1.89 (m, 2H, CH₂), 1.05–1.04 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 186.9, 173.1, 159.9, 156.4, 135.1, 129.0, 113.6, 86.6, 55.6, 39.9, 38.4, 36.3, 30.2, 20.7, 16.6; HRMS (ESI) m/z calcd for C₁₇H₂₁N₂O₃ [M + H]⁺, 301.1547; found, 301.1547.

9-(4-Chlorobenzoyl)-7-methyl-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyrimidin-6-one (4c). White solid: mp 135–136 °C; IR (KBr): 3439, 2966, 1698, 1612, 1542, 1402, 1241, 1177, 841 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 12.58 (br, 1H, NH), 7.45 (d, J = 8.3 Hz, 2H, PhH), 7.36 (d, J = 8.3 Hz, 2H, PhH), 3.83–3.44 (m, 2H, NCH₂), 3.38–3.36 (m, 2H, NCH₂), 2.50–2.39 (m, 2H, CH₂), 2.31–2.26 (m, H, CH), 1.95–1.90 (m, 2H, CH₂), 1.05–1.03 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 185.6, 173.1, 156.8, 141.4, 133.4, 129.2, 128.4, 86.7, 39.6, 38.4, 36.3, 29.8, 20.5, 15.6; HRMS (ESI) m/z calcd for C₁₆H₁₈ClN₂O₂ [M + H]⁺, 305.1051; found, 305.1052.

9-(4-Fluorobenzoyl)-7-methyl-1,2,3,4,7,8-hexahydro-6H-pyrido-[1,2-a]pyrimidin-6-one (4d). Light yellow solid: mp 157–158 °C; IR (KBr): 3450, 3073, 2974, 1698, 1654, 1535, 1241, 1158, 847, 600 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 12.58 (br, 1H, NH), 7.40–7.38 (m, 2H, PhH), 7.22–7.19 (m, 2H, PhH), 3.85–3.58 (m, 2H, NCH₂), 3.45–3.36 (m, 2H, NCH₂), 2.49–3.46 (m, H, CH), 2.42–2.27 (m, 2H, CH₂), 1.96–1.89 (m, 2H, CH₂), 1.04 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 185.9, 173.2, 162.4 (d, J = 244.5 Hz), 156.7, 139.2, 129.5, 115.2 (d, J = 21.0 Hz), 86.6, 39.6, 38.4, 36.3, 29.9, 20.6, 15.6; HRMS (ESI) m/z calcd for C₁₆H₁₈FN₂O₂ [M + H]⁺, 289.1347; found, 289.1349.

7-Methyl-9-nitro-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyri-midin-6-one (4e). Yellow solid: mp 228–232 °C; IR (KBr): 3395, 2976, 1705, 1623, 1500, 1394, 1243, 1140, 994, 811 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 11.75 (br, 1H, NH), 3.92–3.68 (m, 2H, NCH₂), 3.54–3.47 (m, 2H, NCH₂), 2.30–2.26 (m, H, CH), 2.64–2.47 (m, 2H, CH₂), 2.04–1.99 (m, 2H, CH₂), 1.24 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 172.3, 152.5, 106.3b 39.7, 39.1, 35.2b 27.9, 20.0, 15.5; HRMS (ESI) m/z calcd for C₉H₁₄N₃O₃ [M + H]⁺, 212.1030; found, 212.1030.

10-(4-Methoxybenzoyl)-8-methyl-2,3,4,5,8,9-hexahydropyrido[1,2-a][1,3]diazepin-7(1H)-one (4f). White solid: mp 126–127.5 °C; IR (KBr):3416, 2937, 1694, 1601, 1434, 1258, 1149, 999, 900, 642 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ = 11.63 (br, 1H, NH), 7.41 (d, J = 8.6 Hz, 2H, PhH), 6.92 (d, J = 8.3 Hz, 2H, PhH), 4.44–3.51 (m, 2H, NCH₂), 3.85 (s, 3H, OCH₃), 3.47–3.31 (m, 2H, NCH₂), 2.63–2.31 (m, 2H, CH₂), 2.50–2.42 (m, H, CH), 2.03–1.79 (m, 4H, CH₂CH₂), 1.18–1.16 (m, 3H, CH₃); ¹³C NMR (125 MHz, CDCl₃): δ = 190.6, 174.5, 161.9, 160.3, 134.4, 128.7, 113.2, 92.5, 55.2, 45.1, 44.9, 37.8, 30.6, 26.5, 26.2, 14.6; HRMS (ESI) m/z calcd for C₁₈H₂₃N₂O₃ [M + H]⁺, 315.1703; found, 315.1707.

10-Benzoyl-8-methyl-2,3,4,5,8,9-hexahydropyrido[1,2-a][1,3]-diazepin-7(1H)-one (4g). White solid: mp 131–132 °C; IR (KBr): 3438, 2937, 1697, 1602, 1473, 1432, 1242, 1150, 997, 708 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 11.66 (br, 1H, NH), 7.31 (m, 5H, PhH), 4.33–3.45 (m, 2H, NCH₂), 3.41–3.25 (m, 2H, NCH₂), 2.47–2.35 (m, 2H, CH₂), 2.23–2.18 (m, H, CH), 1.81–1.71 (m, 4H, CH₂CH₂), 1.08–1.06 (d, J = 6.7 Hz, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 191.0, 174.6, 162.1, 142.1, 129.1, 128.1, 126.8, 92.4, 45.2, 44.9, 37.8, 30.3, 26.5, 26.1, 14.7; HRMS (ESI) m/z calcd for C₁₇H₂₁N₂O₂ [M + H]⁺, 285.1598; found, 285.1598.

6-Methyl-8-(4-methylbenzoyl)-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (4h). White solid: mp 162.5–164 °C; IR (KBr): 3291, 2962, 2817, 1686, 1634, 1525, 1439, 1286, 1033, 750 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 9.34 (br, 1H, NH), 7.30 (d, J = 8.0 Hz, 2H, PhH), 7.20 (d, J = 7.9 Hz, 2H, PhH), 3.88–3.67 (m, 4H, NCH₂CH₂), 3.34 (s, 3H, CH₃), 2.59–2.56 (m, H, CH), 2.51–2.40 (m, 2H, CH₂), 1.07–1.06 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 189.1, 172.0, 156.5, 139.5, 139.0, 128.9, 127.4, 84.4, 43.3, 42.2, 36.8, 30.9, 21.4, 15.6; HRMS (ESI) m/z calcd for C₁₆H₁₉N₂O₂ [M + H]⁺, 271.1441; found, 271.1444.

8-Benzoyl-6-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5-(1H)-one (4i). White solid: mp 144.5–145.5 °C; IR (KBr): 3320, 2970, 1689, 1632, 1526, 1382, 1285, 1211, 1035, 736 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 9.38 (br, 1H, NH), 7.42–7.38 (m, 5H, PhH), 3.89–3.68 (m, 4H, NCH₂CH₂), 2.58–2.55 (m, H, CH), 2.54–2.40 (m, 2H, CH₂), 1.08–1.07 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 189.1, 172.0, 156.6, 142.3, 129.4, 128.4, 127.2, 84.3, 43.3, 42.2, 36.8, 30.8, 15.6; HRMS (ESI) m/z calcd for C₁₅H₁₇N₂O₂ [M + H]⁺, 257.1285; found, 257.1284.

8-(4-Methoxybenzoyl)-6-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (4j). White solid: mp 164–165 °C; IR (KBr): 3416, 3285, 2971, 1683, 1633, 1577, 1496, 1289, 1167, 1022, 841 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 9.33 (br, 1H, NH), 7.40 (d, J = 8.7 Hz, 2H, PhH), 6.95 (d, J = 8.7 Hz, 2H, PhH), 3.89–3.67 (m, 4H, NCH₂CH₂), 3.79 (s, 3H, OCH₃), 2.64–2.62 (m, H, CH), 2.52–2.45 (m, 2H, CH₂), 1.09–1.08 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 188.5, 172.0, 160.4, 156.4, 134.6, 129.2, 113.6, 84.4, 55.6, 43.3, 42.2, 36.8, 31.1, 15.6; HRMS (ESI) m/z calcd for C₁₆H₁₉N₂O₃ [M + H]⁺, 287.1390; found, 287.1392.

8-(4-Chlorobenzoyl)-6-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (4k). White solid: mp 191.5–192.5 °C; IR (KBr): 3424, 2975, 1683, 1635, 1504, 1439, 1292, 1024, 758 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ = 9.44 (br, 1H, NH), 7.42–7.37 (m, 4H, PhH), 4.07–3.83 (m, 4H, NCH₂CH₂), 2.73–2.69 (m, H, CH), 2.57–2.45 (m, 2H, CH₂), 1.24–1.22 (s, 3H, CH₃); ¹³C NMR (125 MHz, CDCl₃): δ = 189.9, 172.6, 157.6, 140.0, 135.7, 128.8, 128.6, 85.4, 43.3, 42.5, 37.5, 31.1, 15.7; HRMS (ESI) m/z calcd for C₁₅H₁₆ClN₂O₂ [M + H]⁺, 291.0895; found, 291.0894.

8-(2-Chlorobenzoyl)-6-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (4l). White solid: mp 171–173 °C; IR (KBr): 3415, 3306, 2966, 1691, 1634, 1513, 1283, 1036, 752 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 9.23 (br, 1H, NH), 7.32–7.31 (m, H, PhH), 7.23–7.20 (m, 2H, PhH), 7.16–7.14 (m, H, PhH), 3.98–3.77 (m, 4H, NCH₂CH₂), 2.51–2.48 (m, H, CH), 2.32–2.16 (m, 2H, CH₂), 1.13–1.12 (s, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 189.9, 172.3, 156.7, 140.7, 130.1, 129.6, 129.5, 127.7, 126.9, 85.5, 42.9, 42.1, 37.0, 29.1, 15.4; HRMS (ESI) m/z calcd for C₁₅H₁₆ClN₂O₂ [M + H]⁺, 291.0895; found, 291.0897.

8-(4-Fluorobenzoyl)-6-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (4m). Yellow solid: mp 154–155 °C; IR (KBr): 3415, 3311, 2979, 1683, 1637, 1600, 1441, 1286, 1155, 1034, 840 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ = 9.41 (br, 1H, NH), 7.49–7.46 (m, 2H, PhH), 7.11–7.08 (m, 2H, PhH), 4.08–3.84 (m, 4H, NCH₂CH₂), 2.75–2.72 (m, H, CH), 2.58–2.48 (m, 2H, CH₂), 1.25–1.24 (s, 3H, CH₃); ¹³C NMR (125 MHz, CDCl₃): δ = 190.1, 172.6, 163.7 (d, J = 248.0 Hz), 157.6, 137.7, 129.6, 115.4 (d, J = 21.0 Hz), 85.4, 43.3, 42.5, 37.6, 31.1, 15.7; HRMS (ESI) m/z calcd for C₁₅H₁₆FN₂O₂ [M + H]⁺, 275.1190; found, 275.1191.

6-Methyl-8-nitro-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (4n). Yellow solid: mp 240–250 °C; IR (KBr): 3415, 3238, 2989, 1700, 1625, 1491, 1376, 1289, 1184, 685 cm⁻¹; ¹H NMR (600 MHz, DMSO-d₆): δ = 9.53 (br, 1H, NH), 3.92–3.70 (m, 4H, NCH₂CH₂), 3.11–3.07 (m, H, CH), 2.74–2.43 (m, 2H, CH₂), 1.17–1.16 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 171.4, 153.0, 103.3, 43.8, 43.2, 35.6, 28.9, 15.8; HRMS (ESI) m/z calcd for C₈H₁₂N₃O₃ [M + H]⁺, 198.0873; found, 198.0875.

9-(4-Methoxybenzoyl)-8-methyl-1,2,3,4,7,8-hexahydro-6H-pyr-ido[1,2-a]pyrimidin-6-one (5a). White solid: mp 154–156.5 °C; IR (KBr): 3415, 2967, 1693, 1654, 1446, 1316, 1169, 1032, 837 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆): δ = 12.69 (br, 1H, NH), 7.25 (d, J = 8.5 Hz, 2H, PhH), 6.93 (d, J = 8.5 Hz, 2H, PhH), 3.93–3.52 (m, 2H, NCH₂), 3.78 (s, 3H, OCH₃), 3.57–3.34 (m, 2H, NCH₂), 2.81–2.77 (m, 2H, CH₂), 2.32–2.28 (m, H, CH), 1.94–1.93 (m, 2H, CH₂), 0.82–0.81 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 187.7, 169.6, 159.4, 155.7, 135.5, 128.1, 113.6, 92.4, 55.5, 39.9, 38.8, 38.4, 26.2, 21.3, 20.5; HRMS (ESI) m/z calcd for C₁₇H₂₁N₂O₃ [M + H]⁺, 301.1547; found, 301.1549.

9-Benzoyl-8-methyl-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]py-rimidin-6-one (5b). White solid: mp 125–127.5 °C; IR (KBr): 3416, 2957, 1698, 1611, 1536, 1449, 1277, 1159, 713, 696 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆): δ = 12.58 (br, 1H, NH), 7.41–7.34 (m, 3H, PhH), 7.29–7.27 (m, 2H, PhH), 3.93–3.53 (m, 2H, NCH₂), 3.47–3.35 (m, 2H, NCH₂), 2.80–2.67 (m, 2H, CH₂), 2.31–2.27 (m, H, CH), 1.94–1.93 (m, 2H, CH₂), 0.81–0.80 (m, 3H, CH₃); ¹³C NMR (150 MHz, DMSO-d₆): δ = 188.0, 169.6, 155.8, 143.0, 128.3, 126.3, 92.3, 39.4, 38.8, 38.4, 26.1, 21.3, 20.4; HRMS (ESI) m/z calcd for C₁₆H₁₉N₂O₂ [M + H]⁺, 271.1441; found, 271.1442.

9-(4-Chlorobenzoyl)-8-methyl-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyrimidin-6-one (5c). White solid: mp 135.5–136.5 °C; IR (KBr): 3438, 2959, 1696, 1618, 1541, 1384, 1275, 1155, 837, 674 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 12.66 (br, 1H, NH), 7.28 (d, J = 8.0 Hz, 2H, PhH), 7.21 (d, J = 7.9 Hz, 2H, PhH), 4.03–3.55 (m, 2H, NCH₂), 3.45–3.35 (m, 2H, NCH₂), 2.73–2.61 (m, 2H, CH₂), 2.36–2.35 (m, H, CH), 1.99–1.95 (m, 2H, CH₂), 0.85 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 188.0, 169.8, 156.0, 140.7, 134.1, 128.4, 127.7, 93.0, 39.6, 38.8, 38.6, 26.2, 21.1, 20.6; HRMS (ESI) m/z calcd for C₁₆H₁₈ClN₂O₂ [M + H]⁺, 305.1051; found, 305.1049.

9-(4-Fluorobenzoyl)-8-methyl-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyrimidin-6-one (5d). Yellow solid: mp 130–132 °C; IR (KBr): 3437, 2958, 1697, 1599, 1529, 1383, 1153, 836 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 12.68 (br, 1H, NH), 7.26–7.24 (m, 2H, PhH), 7.00–6.97 (m, 2H, PhH), 4.03–3.54 (m, 2H, NCH₂), 3.45–3.35 (m, 2H, NCH₂), 2.75–2.72 (m, H, CH), 2.66–2.38 (m, 2H, CH₂), 1.99–1.95 (m, 2H, CH₂), 0.85–0.84 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 188.3, 169.8, 162.6 (d, J = 246.0 Hz), 156.0, 138.5, 128.1, 115.1 (d, J = 21.0 Hz), 93.0, 39.6, 38.8, 38.6, 26.2, 21.0, 20.7; HRMS (ESI) m/z calcd for C₁₆H₁₈FN₂O₂ [M + H]⁺, 289.1347; found, 289.1346.

8-Methyl-9-nitro-1,2,3,4,7,8-hexahydro-6H-pyrido[1,2-a]pyr-imidin-6-one (5e). Yellow solid: mp 212–214.5 °C; IR (KBr): 3408, 3073, 2960, 1713, 1617, 1511, 1391, 1161, 1051, 955, 784 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 4.03–3.63 (m, 2H, NCH₂), 3.62–3.53 (m, 2H, NCH₂), 3.52–2.46 (m, H, CH), 2.74–2.51 (m, 2H, CH₂), 2.04–1.99 (m, 2H, CH₂), 1.73 (br, 1H, NH), 1.06 (d, J = 6.9 Hz, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 168.9, 151.8, 111.4, 39.3, 39.1, 38.0, 26.3, 19.9, 17.4; HRMS (ESI) m/z calcd for C₉H₁₄N₃O₃ [M + H]⁺, 212.1030; found, 212.1030.

10-(4-Methoxybenzoyl)-9-methyl-2,3,4,5,8,9-hexahydropyrido[1,2-a][1,3]diazepin-7(1H)-one (5f). Light yellow solid: mp 162.5–163.5 °C; IR (KBr): 3449, 2953, 1695, 1697, 1474, 1432, 1266, 1149, 1000, 849 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 11.40 (br, 1H, NH), 7.27 (d, J = 8.6 Hz, 2H, PhH), 6.83 (d, J = 8.6 Hz, 2H, PhH), 4.61–3.46 (m, 2H, NCH₂), 3.76 (s, 3H, OCH₃), 3.12–3.08 (m, 2H, NCH₂), 2.86–2.62 (m, 2H, CH₂), 2.35–2.32 (m, H, CH), 1.85–1.65 (m, 4H, CH₂CH₂), 0.85 (d, J = 7.0 Hz, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 191.6, 171.3, 161.4, 160.2, 134.9, 128.1, 113.4, 98.8, 55.3, 45.4, 44.8, 40.8, 26.9, 26.8, 26.6, 19.5; HRMS (ESI) m/z calcd for C₁₈H₂₃N₂O₃ [M + H]⁺, 315.1703; found, 315.1705.

10-Benzoyl-9-methyl-2,3,4,5,8,9-hexahydropyrido[1,2-a][1,3]diazepin-7(1H)-one (5g). White solid: mp 157–159.5 °C; IR (KBr): 3290, 3066, 2951, 1696, 1596, 1471, 1310, 1147, 1004, 799, 710 cm⁻¹; ¹H NMR (600 MHz, CDCl₃ + DMSO-d₆): δ = 7.05–6.97 (m, 5H, PhH), 4.32–3.24 (m, 2H, NCH₂), 2.94–2.69 (m, 2H, NCH₂), 2.46–2.42 (m, H, CH), 2.38–2.00 (m, 2H, CH₂), 1.59–1.39 (m, 4H, CH₂CH₂), 1.44 (br, 1H, NH), 0.56 (d, J = 6.9 Hz, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃ + DMSO-d₆): δ = 190.6, 170.1, 160.7, 141.5, 127.7, 127.3, 125.1, 97.3, 44.4, 43.8, 39.8, 38.0, 25.7, 25.6, 18.7; HRMS (ESI) m/z calcd for C₁₇H₂₁N₂O₂ [M + H]⁺, 285.1598; found, 285.1596.

7-Methyl-8-(4-methylbenzoyl)-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (5h). White solid: mp 173–176 °C; IR (KBr): 3449, 3299, 2957, 1694, 1625, 1528, 1371, 1320, 1201, 1025, 769 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ = 9.50 (br, 1H, NH), 7.32 (d, J = 7.8 Hz, 2H, PhH), 7.21 (d, J = 7.7 Hz, 2H, PhH), 4.12–3.77 (m, 4H, NCH₂CH₂), 3.09–3.07 (m, H, CH), 2.76–2.43 (m, 2H, CH₂), 2.39 (s, 3H, CH₃), 0.97–0.96 (m, 3H, CH₃); ¹³C NMR (125 MHz, CDCl₃): δ = 191.9, 168.8, 156.0, 138.9, 128.9, 126.4, 91.5, 42.5, 41.7, 39.7, 27.4, 22.0, 21.3; HRMS (ESI) m/z calcd for C₁₆H₁₉N₂O₂ [M + H]⁺, 271.1441; found, 271.1440.

8-Benzoyl-7-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (5i). White solid: mp 138–139 °C; IR (KBr): 3289, 2958, 1695, 1625, 1524, 1439, 1328, 1207, 0127, 700 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 9.43 (br, 1H, NH), 7.31 (m, 5H, PhH), 4.04–3.71 (m, 4H, NCH₂CH₂), 2.96–2.93 (m, H, CH), 2.67–2.33 (m, 2H, CH₂), 0.88–0.87 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 192.0, 168.9, 156.2, 141.7, 129.0, 128.2, 126.4, 91.5, 42.6, 41.8, 39.8, 27.5, 19.6; HRMS (ESI) m/z calcd for C₁₅H₁₇N₂O₂ [M + H]⁺, 257.1285; found, 257.1286.

8-(4-Chlorobenzoyl)-7-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (5j). White solid: mp 144–145.5 °C; IR (KBr): 3415, 3316, 2945, 1691, 1625, 1520, 1445, 1329, 1025, 671 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ = 9.53 (br, 1H, NH), 7.39–7.35 (m, 4H, PhH), 4.13–3.80 (m, 4H, NCH₂CH₂), 3.01–2.99 (m, H, CH), 2.76–2.43 (m, 2H, CH₂), 0.97–0.96 (m, 3H, CH₃); ¹³C NMR (125 MHz, CDCl₃): δ = 190.8, 169.1, 156.9, 140.4, 135.3, 128.8, 128.3, 91.8, 43.0, 42.3, 40.1, 27.9, 22.5; HRMS (ESI) m/z calcd for C₁₅H₁₆ClN₂O₂ [M + H]⁺, 291.0895; found, 291.0898.

8-(2-Chlorobenzoyl)-7-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (5k). White solid: mp 228–229 °C; IR (KBr): 3415, 3319, 2959, 1697, 1630, 1529, 1375, 1208, 1027, 755 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 9.30 (br, 1H, NH), 7.31–7.18 (m, 4H, PhH), 4.05–3.75 (m, 4H, NCH₂CH₂), 2.68–2.58 (m, 2H, CH₂), 2.35–2.32 (m, H, CH), 0.84–0.83 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 189.0, 168.9, 156.1, 140.5, 130.2, 129.5, 127.8, 126.8, 91.8, 42.7, 41.8, 39.8, 27.4, 21.8; HRMS (ESI) m/z calcd for C₁₅H₁₆ClN₂O₂ [M + H]⁺, 291.0895; found, 291.0896.

8-(4-Fluorobenzoyl)-7-methyl-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (5l). Yellow solid: mp 143–144.5 °C; IR (KBr): 3290, 2961, 1703, 1622, 1527, 1371, 1226, 1026, 851, 772 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆): δ = 9.39 (br, 1H, NH), 7.44–7.41 (m, 2H, PhH), 7.24–7.21 (m, 2H, PhH), 3.93–3.63 (m, 4H, NCH₂CH₂), 2.88–2.75 (m, 2H, CH₂), 2.27–2.24 (m, H, CH), 0.95–0.83 (s, 3H, CH₃); ¹³C NMR (125 MHz, DMSO-d₆): δ = 188.6, 168.5, 162.4 (d, J = 243.0 Hz), 155.8, 139.1, 129.0, 115.2 (d, J = 21.0 Hz), 90.5, 42.9, 41.8, 39.4, 27.6, 22.2; HRMS (ESI) m/z calcd for C₁₅H₁₆FN₂O₂ [M + H]⁺, 275.1190; found, 275.1191.

1-(4-Fluorobenzyl)-6-methyl-8-nitro-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (6a). Yellow solid: mp 188–189 °C; IR (KBr): 3415, 3063, 2974, 1711, 1609, 1436, 1380, 1221, 1156, 832 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 7.23–7.21 (m, 2H, PhH), 7.00–6.97 (m, 2H, PhH), 4.79 (d, J = 15 Hz, H, NCH), 4.73 (d, J = 15 Hz, H, NCH), 3.92–3.57 (m, 4H, NCH₂CH₂), 3.33–2.28 (m, H, CH), 2.63–2.59 (m, 2H, CH₂), 1.22–1.21 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 171.7, 162.7 (d, J = 246.0 Hz), 151.8, 130.5, 130.1, 116.0 (d, J = 21.0 Hz), 105.2, 54.3, 49.3, 41.3, 36.4, 30.8, 15.2; HRMS (ESI) m/z calcd for C₁₅H₁₇FN₃O₃ [M + H]⁺, 306.1248; found, 306.1249.

4-((6-Methyl-8-nitro-5-oxo-2,3,6,7-tetrahydroimidazo[1,2-a]py-ridin-1(5H)-yl)methyl)benzonitrile (6b). Yellow solid: mp 166.5–167.5 °C; IR (KBr): 3432, 2978, 2230, 1694, 1606, 1255, 1189, 927, 823, 550 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 7.60 (d, J = 8.2 Hz, 2H, PhH), 7.40 (d, J = 8.1 Hz, 2H, PhH), 4.90 (d, J = 15.8 Hz, H, NCH), 4.79 (d, J = 15.7 Hz, H, NCH), 3.99–3.58 (m, 4H, NCH₂CH₂), 3.30–2.28 (m, H, CH), 2.64–2.60 (m, 2H, CH₂), 1.23–1.19 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 171.6, 151.9, 140.4, 132.7, 128.5, 118.3, 112.2, 105.6, 55.0, 50.1, 41.4, 36.3, 30.7, 15.1; HRMS (ESI) m/z calcd for C₁₆H₁₇N₄O₃ [M + H]⁺, 313.1295; found, 313.1296.

1-(4-Fluorobenzyl)-7-methyl-8-nitro-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one (6c). Yellow solid: mp 150–152 °C; IR (KBr): 3394, 2953, 1710, 1590, 1437, 1145, 758, 597 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ = 7.17–7.16 (m, 2H, PhH), 6.99–6.96 (m, 2H, PhH), 4.82–4.65 (m, 2H, NCH), 3.99–3.60 (m, 4H, NCH₂CH₂), 3.58–3.56 (m, H, CH), 2.74–2.41 (m, 2H, CH₂), 1.00–0.99 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃ + DMSO-d₆): δ = 172.4, 167.1 (d, J = 244.5 Hz), 155.5, 135.8, 134.7, 120.4 (d, J = 21.0 Hz), 115.7, 58.6, 54.9, 45.9, 43.3, 34.1, 23.8; HRMS (ESI) m/z calcd for C₁₅H₁₇FN₃O₃ [M + H]⁺, 306.1248; found, 306.1244.

4-((7-Methyl-8-nitro-5-oxo-2,3,6,7-tetrahydroimidazo[1,2-a]py-ridin-1(5H)-yl)methyl)benzonitrile (6d). Yellow solid: mp 163.5–164.5 °C; IR (KBr): 3438, 2966, 2230, 1705, 1598, 1309, 1138, 757, 564 cm⁻¹; ¹H NMR (600 MHz, CDCl₃): δ = 7.59 (d, J = 8.0 Hz, 2H, PhH), 7.35 (d, J = 7.9 Hz, 2H, PhH), 4.85–4.79 (m, 2H, NCH₂), 4.04–3.60 (m, 4H, NCH₂CH₂), 3.58–3.53 (m, H, CH), 2.74–2.42 (m, 2H, CH₂), 1.01–1.00 (m, 3H, CH₃); ¹³C NMR (150 MHz, CDCl₃): δ = 167.8, 150.4, 140.5, 132.7, 128.4, 118.3, 112.2, 111.6, 54.8, 50.4, 41.1, 38.5, 29.3, 19.2; HRMS (ESI) m/z calcd for C₁₆H₁₇N₄O₃ [M + H]⁺, 313.1295; found, 313.1292.

Acknowledgements

This work was supported by the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13095), the Program for the National Natural Science Foundation of China (No. U1202221, 21362042, 21262042, 21662042), the Talent Found in Yunnan Province (2012HB001), Excellent Young Talents, Yunnan University (XT412003), High-Level Talents Introduction Plan of Yunnan Province (CB143001), the Scientific Research Fund of Yunnan Provincial Education Department (2016zzx004).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1503692 (4j). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra23451h

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