Access to 6-arylpyrrolo[2,3-d]pyrimidines via a palladium-catalyzed direct C–H arylation reaction

Abstract

An efficient method of palladium-catalyzed direct arylation has been developed for the selective functionalization of the C6 position of 2,4-diarylpyrrolo[2,3-d]pyrimidines. Under optimal conditions, various aryl bromides successfully provided a wide range of 6-arylpyrrolo[2,3-d]pyrimidines.

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Introduction

Pyrrolo[2,3-d]pyrimidine, and its aryl and heteroaryl derivatives, display a wide range of biological activities, such as inhibition of protein kinases,¹ thymidylate synthase² and dihydrofolate reductase,³ antitumor⁴ and antimicrobial properties,⁵ antagonist effects on receptors,⁶ and cytostatic and antiproliferative effects.^6a,7 Examples of synthetic biologically active compounds possessing a pyrrolo[2,3-d]pyrimidine core include EGFR-tyrosine kinases inhibitor AEE-788,⁸ ACK1 inhibitors⁴ and GSK-3β inhibitors that induce neurogenesis (TWS119)⁹ (Fig. 1).

Fig. 1 Biologically active pyrrolo[2,3-d]pyrimidines.

In addition to these applications, oligoarylenes with a pyrrolo[2,3-d]pyrimidine core exhibit strong UV-blue fluorescence and are promising candidates as fluorescent functional materials.¹⁰ Moreover, some pyrrolo[2,3-d]pyrimidine derivatives form fluorescent nanoaggregates and show aggregation-induced emission enhancement.¹¹ Compounds possessing a functionalized pyrrolo[2,3-d]pyrimidine scaffold can be prepared by cyclocondensation reactions starting either from the appropriately substituted pyrrole^5b,12 or pyrimidine^6c,13 derivatives as common intermediates. However, these strategies often require multistep syntheses, and thus the synthesis of polysubstituted pyrrolopyrimidines using such methods tends to be lengthy. On the other hand, pyrrolo[2,3-d]pyrimidine can be functionalized using late-stage functionalization methods, such as transition metal-catalyzed cross-coupling reactions. Generally, such methods allow the introduction of different aryl moieties into various positions of the heterocycle and diversely functionalized pyrrolo[2,3-d]pyrimidines can be obtained in good yields.^{3,4,10,13e,14} Despite significant advances in cross-coupling reactions, multiple steps are usually required for installing active groups and none of the preactivation groups appears in the final product. Therefore, in recent years direct arylation reactions that are more atom-economic and step-simplified have emerged as attractive alternatives to these more commonly employed cross-coupling reactions.¹⁵ Although direct arylation has been demonstrated on a wealth of aromatic heterocycles so far, there remains a multitude of heteroaromatic ring systems that have not been investigated, including pyrrolo[2,3-d]pyrimidine. To the best of our knowledge, the only attempt to synthesize 6-arylpyrrolopyrimidines by direct arylation of 7-benzyl-4-phenylpyrrolo[2,3-d]pyrimidine with iodoarenes and heteroarenes was made by Hocek and co-workers.^14a However, the reaction gave products (3 examples) in low 35–41% yields, or did not take place. Because the pyrrolo[2,3-d]pyrimidine ring system represents an important pharmacophore in drug discovery and its aryl derivatives possess valuable photophysical properties, efficient and economic methods for the synthesis of arylpyrrolo[2,3-d]pyrimidines are highly desirable. Therefore, we have investigated the direct arylation of pyrrolopyrimidines to provide easy access to 6-arylpyrrolo[2,3-d]pyrimidines.

Results and discussion

Initially, our efforts were focused on identifying the catalytic system and reaction conditions for the direct arylation of compound 1a with 4-iodoanisole (Table 1). We began by arylating pyrrolo[2,3-d]pyrimidine 1a with the catalyst system used by Hocek and co-workers.^14a After heating the reaction mixture at 170 °C for 72 h in the presence of Pd(OAc)₂/CuI/Cs₂CO₃, product 2a was obtained in a low yield of 21% (Table 1, entry 1). A slightly higher yield for 2a (34%) was obtained when a catalyst system composed of Pd(OAc)₂, P(2-biPh)Cy₂ and K₂CO₃ was employed (Table 1, entry 2). These results together with the previously reported results,^14a,16 indicate that the catalyst system suitable for the direct arylation of purines does not work well in a pyrrolo[2,3-d]pyrimidine series. Otherwise, conditions similar to Fagnou and co-workers' direct heteroaryl arylation procedure¹⁷ allowed the direct C6 arylation of pyrrolo[2,3-d]pyrimidine 1a to proceed at 170 °C and provided 2a in 80% yield (Table 1, entry 3). Decreasing the loading of the catalyst from 5 to 2 mol% led to a lower yield of compound 2a (40%) (Table 1, entry 4). It is also interesting to note the role of pivalic acid; the reaction performed without pivalic acid under the same conditions furnished 2a in only 46% yield (Table 1, entry 5). Addition of pivalic acid (30 mol%) to the catalyst system Pd(OAc)₂/P(2-biPh)Cy₂/K₂CO₃ also increased the reactivity of 1a, and product 2a was obtained in 51% yield (Table 1, compare entry 6 with entry 2).

Table 1 Optimization of direct C6 arylation of pyrrolopyrimidine 1a^a

Entry	RC6H4X	Reaction conditions	Yield^b, %
a Unless otherwise specified, all reactions were carried out using 5 mol% Pd(OAc)2, 10 mol% PCy3·HBF4 or P(2-biPh)Cy2, 30 mol% PivOH, 1.5 equiv. RC6H4X, 3 equiv. K2CO3 in DMA at 170 °C, 72 h, argon.b Isolated yields.c 5 mol% Pd(OAc)2, 3 equiv. CuI, 2 equiv. RC6H4X, 2.5 equiv. Cs2CO3 argon.d 2 mol% Pd(OAc)2, 4 mol% PCy3·HBF4.e The rest of 1a recovered.
1	4-MeOC6H4I	Pd(OAc)2, CuI, Cs2CO3	2a, 21^c
2	4-MeOC6H4I	Pd(OAc)2, P(2-biPh)Cy2, K2CO3	2a, 34
3	4-MeOC6H4I	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3	2a, 80
4	4-MeOC6H4I	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3	2a, 40^d
5	4-MeOC6H4I	Pd(OAc)2, PCy3·HBF4, K2CO3	2a, 46
6	4-MeOC6H4I	Pd(OAc)2, P(2-biPh)Cy2, PivOH, K2CO3	2a, 51
7	4-MeOC6H4I	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3, Ag2CO3	2a, 78
8	4-MeOC6H4Br	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3	2a, 79
9	4-MeOC6H4Br	Pd(OAc)2, PCy3, PivOH, K2CO3	2a, 2^e
10	4-MeOC6H4Br	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3, dioxane	2a, 10^e
11	4-CNC6H4I	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3	2b, 17
12	4-CNC6H4Br	Pd(OAc)2, PCy3·HBF4, PivOH, K2CO3	2b, 50

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Fagnou and co-workers established that the reactivity of aryl iodides is sometimes reduced by the accumulation of iodide anions in the reaction mixture, and that this catalyst poisoning can be overcome by adding AgOTf or Ag₂CO₃ to the reaction mixture.¹⁸ However, in our case, addition of Ag₂CO₃ was useless and product 2a was obtained almost in the same yield (Table 1, entry 7).

In order to compare the reactivity of aryl bromides and aryl iodides, we decided to examine the reaction of pyrrolo[2,3-d]pyrimidine 1a with 4-bromoanisole using the same catalytic system, Pd(OAc)₂/PCy₃·HBF₄/PivOH/K₂CO₃/DMA. After 72 h heating at 170 °C the desired product was obtained in 79% yield (Table 1, entry 8). However, when free tricyclohexylphosphine was used as a ligand, only traces of target compound 2a were isolated (Table 1, entry 9). Changing the reaction solvent from DMA to dioxane resulted in the formation of compound 2a in only 10% yield (Table 1, entry 10). To clarify the reactivity of aryl iodides and bromides with electron-withdrawing groups, C–H arylation using 4-iodo or 4-bromo benzonitrile was carried out. In contrast to 4-iodoanisole, 4-iodobenzonitrile reacted with pyrrolo[2,3-d]pyrimidine 1a very poorly and compound 2b was obtained in only 17% yield (Table 1, entry 11). Moreover, along with the target C6-arylated product 2b, 5,5′-bipyrrolo[2,3-d]pyrimidine 3 was also isolated.

Meanwhile, 4-bromobenzonitrile under the same reaction conditions furnished the C6 arylation product 2b in 50% yield (Table 1, entry 12). Finally, brief screening of the bases Cs₂CO₃, K₂CO₃, KOAc and AgOAc revealed that K₂CO₃ was the most suitable base for the C6 arylation reaction of pyrrolo[2,3-d]pyrimidine.

Having established that the optimal reaction conditions were Pd(OAc)₂/PCy₃·HBF₄/PivOH as the catalyst system, K₂CO₃ as the base and DMA as the solvent, we next turned our attention to the scope of the direct arylation of 7-methyl-2,4-diarylpyrrolo[2,3-d]pyrimidines (1a–c) with aryl bromides, because of their stability and ease of preparation on the laboratory scale.

As shown in Scheme 1, a variety of aryl bromides with either electron-donating or electron-withdrawing groups attached at the ortho- and/or para-positions of the benzene ring were able to undergo arylation and furnished the corresponding products 2a–s in moderate to good yields. The reaction showed good compatibility with many valuable functional groups, including methoxy, cyano, nitro, dimethylamino, fluoro, and trifluoromethyl substituents. Pyrrolo[2,3-d]pyrimidines also reacted with sterically encumbered aryl bromides, such as 2-bromotoluene, 1-bromo-2,6-dimethylbenzene or 1-bromo-2,4-di(trifluoromethyl)benzene to afford the corresponding products 2k–m and 2p in 50–79% yields.

Scheme 1 Scope of C6 arylation of 7-methyl-2,4-diarylpyrrolo[2,3-d]pyrimidines. (a) Reaction conditions (isolated yields): compound 1a–c (70 mg), Pd(OAc)₂ (5 mol%), PCy₃·HBF₄ (10 mol%), PivOH (30 mol%), aryl halide (1.5 equiv.), K₂CO₃ (3 equiv.), DMA. (b) Compound 3 (7–10 mg) was also isolated. (c) Compound 4 (4 mg) was also isolated.

The arylation reaction of pyrrolo[2,3-d]pyrimidines 1a–c can occur at position 5 or 6 of the pyrrolopyrimidine. However, structural elucidation of the products by NMR spectroscopy showed that the arylation reaction is site-selective and only 6-aryl derivatives were obtained. In the ¹H NMR spectra of compounds 2, the pyrrole 5-H proton signal remains at 6.8–7.0 ppm, almost in the same place as in the starting compounds 1. Moreover, NOESY spectra of the products showed two main types of cross-signal: between the N-methyl group and the ortho-protons of the aromatic ring at position 6; and between the 5-H proton of the pyrrole ring and ortho-protons of the aromatic rings at positions 4 and 6 of the pyrrolopyrimidine. Additionally, in the NOESY spectra no interaction between the N-methyl group protons and the pyrrole ring proton was observed. This incontrovertibly proved that only C6 arylated products were obtained.

Nevertheless, in some cases, the formation of two types of byproducts was observed (Fig. 2). The first one was identified as dimerization product 3. This byproduct in small amounts (up to 7%) was formed in the reaction of pyrrolo[2,3-d]pyrimidine 1a with 1-bromo-4-trifluoromethyl-, 1-bromo-4-dimethylamino- and 1-bromo-2,6-dimethylbenzenes. Compound 3, is probably formed during the side-reaction of the palladium-catalyzed oxidative C5–H activation with Pd(OAc)₂. Another byproduct, 5,6-diarylated derivative 4 (3%), was observed only in the reaction of compound 1a with 4-nitrophenyl bromide (Fig. 2). Formation of these byproducts caused some problems in the purification of the target compounds. Therefore, lower final yields of the corresponding C6 arylation products 2f, 2j, and 2l were obtained.

Fig. 2 Structures of 7,7′-dimethyl-2,2′4,4′-tetraphenyl-7H,7′H-5,5′bipyrrolo[2,3-d]pyrimidine (3) and 7-methyl-5,6-di(4-nitrophenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (4).

The yields of the selective C6 arylation were dramatically lower without a palladium-pivalate co-catalyst combination. These results suggest that the C6 arylation proceeds via a concerted metallation–deprotonation mechanism.¹⁹

Conclusion

In summary, an efficient regioselective Pd-catalyzed direct arylation of 7-methyl-2,4-diarylpyrrolo[2,3-d]pyrimidines with aryl bromides has been developed. The procedure tolerates many functional groups and allows the generation of a wide library of novel pyrrolo[2,3-d]pyrimidine derivatives, including those with π-extended conjugated systems. The results presented here may aid materials and pharmaceutical research programs.

Experimental section

General procedure for the synthesis of 2,4-diaryl-7-methylpyrrolo[2,3-d]pyrimidines 1a–c

A solution of 2,4-dichloro-7-methylpyrrolo[2,3-d]pyrimidine (150 mg, 0.74 mmol) in anhydrous dioxane (5 mL) was flushed with argon and Pd(OAc)₂ (3.32 mg, 0.015 mmol, 2 mol%) and (2-biphenyl)dicyclohexylphosphine (10.4 mg, 0.03 mmol, 4 mol%) were added under stirring and argon flow. After 10 min, arylboronic acid (1.78 mmol, 2.4 equiv.) and K₃PO₄ (0.76 g, 3.56 mmol, 4.8 equiv.) were added. The reaction mixture was stirred under reflux. Then dioxane was evaporated under reduced pressure to dryness and water (5 mL) was added to dissolve inorganic salts. The obtained solution was extracted with chloroform (3 × 25 mL), the organic layer was dried over Na₂SO₄, and the chloroform removed by distillation under reduced pressure. The residue was purified by column chromatography using benzene as an eluent.

7-Methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (1a)

After 15 min, compound 1a was obtained as a yellowish solid (190 mg, 90%), mp 159.8–161.4 °C. Lit.²⁰ mp 159–160 °C. All spectra matched literature values. ¹H NMR (400 MHz, CDCl₃): 4.00 (3H, s, NCH₃), 6.85 [1H, d, J = 4 Hz, 5-H (pp)], 7.25 [1H, d, J = 4 Hz, 6-H (pp)], 7.46–7.63 [6H, m, 2 × 3-5-H (2-Ph, 4-Ph)], 8.31 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.72 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 31.1, 100.3, 113.9, 128.1, 128.4, 128.7, 129.0, 129.6, 129.9, 130.0, 138.8, 139.1, 153.1, 157.0, 157.6 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₁₉H₁₆N₃): 286.1339, found: 286.1342.

2,4-Di(4-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (1b)

After 4 h, compound 1b was obtained as a yellowish solid (182 mg, 71%), mp 138.4–139.7 °C. ¹H NMR (400 MHz, CDCl₃): 3.92 (3H, s, OCH₃), 3.93 (3H, s, OCH₃), 3.96 (3H, s, NCH₃), 6.81 [1H, d, J = 4 Hz, 5-H (pp)], 7.05 [2H, d, J = 8 Hz, 3,5-H (2-Ph)], 7.11 [2H, d, J = 8 Hz, 3,5-H (4-Ph)], 7.19 [1H, d, J = 4 Hz, 6-H (pp)], 8.29 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.66 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 31.0, 55.4, 55.42, 100.3, 112.9, 113.7, 114.1, 129.2, 129.5, 130.5, 131.6, 132.1, 153.1, 156.5, 157.5, 161.0, 161.1 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₁H₂₀N₃O₂): 346.1550, found: 346.1548.

2,4-Di[4-(9H-carbazol-9-yl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (1c)

After 9.5 h, compound 1c was obtained as a reddish solid (410 mg, 90%), mp 284–285.8 °C. ¹H NMR (400 MHz, CDCl₃): 4.08 (3H, s, NCH₃), 7.00 [1H, d, J = 4 Hz, 5-H (pp)], 7.33–7.39 [m, 5H, 6-H (pp), 2 × 3,6-H (2-carb., 4-carb.)], 7.46–7.52 [4H, m, 2 × 2,7-H (2-carb., 4-carb.)], 7.58–7.62 [4H, m, 2 × 1,8-H (2-carb., 4-carb.)], 7.79 [2H, d, J = 8 Hz, 3,5-H (4-Ph)], 7.86 [2H, d, J = 8 Hz, 3,5-H (2-Ph)], 8.20–8.23 [4H, m, 2 × 4,5-H (2-carb., 4-carb.)], 8.61 [2H, d, J = 8.4 Hz, 2,6-H (4-Ph)], 9.00 [2H, d, J = 8.7 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 31.3, 100.3, 109.9, 110.0, 114.1, 120.0, 120.3, 120.4, 120.42, 123.5, 123.7, 126.0, 126.1, 126.9, 127.1, 129.7, 130.56, 130.6, 137.6, 138.1, 138.9, 139.4, 140.7, 140.8, 153.3, 156.1, 157.1 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₄₃H₃₀N₅): 616.2496, found: 616.2490.

General procedure for C–H arylation

7-Methyl-2,4-diphenylpyrrolo[2,3-d]pyrimidine (1a) (70 mg, 0.245 mmol), Pd(OAc)₂ (2.75 mg, 0.0125 mmol, 5 mol%), PCy₃·HBF₄ (9.0 mg, 0.0244 mmol, 10 mol%), PivOH (7.5 mg, 0.0734 mmol, 30 mol%), aryl halide (0.37 mmol, 1.5 equiv.) and K₂CO₃ (100 mg, 0.724 mmol, 3 equiv.) and DMA (1–2 mL) were placed in a screw-cap vial equipped with a magnetic stir bar. The vial was purged with argon and the reaction mixture was stirred vigorously at 170 °C for 72 h. After completion of the reaction, water (10 mL) was added and the aqueous solution was extracted with ethyl acetate (3 × 25 mL). The combined extract was dried with anhydrous Na₂SO₄, ethyl acetate removed by distillation under reduced pressure, and the residue was purified by column chromatography using a gradient of hexane/benzene → benzene.

6-(4-Methoxyphenyl)-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2a)

Product 2a was obtained as a yellow solid (76 mg, 79%), mp 152.2–153.8 °C. ¹H NMR (400 MHz, CDCl₃): 3.92 (3H, s, OCH₃), 3.98 (3H, s, NCH₃), 6.85 [1H, s, 5-H (pp)], 7.07 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 7.48–7.62 [8H, m, 2 × 3-5-H (2-Ph, 4-Ph), 2,6-H (6-Ph)], 8.35 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.74 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 29.9, 55.4, 99.3, 114.27, 114.3, 124.1, 128.0, 128.4, 128.7, 129.0, 129.4, 129.8, 130.4, 139.0, 139.3, 143.0, 154.6, 155.9, 157.2, 160.1 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₆H₂₂N₃O): 392.1757, found: 392.1767.

6-(4-Cyanophenyl)-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2b)

Product 2b was obtained as a yellowish green solid (47 mg, 50%), mp 225–226.3 °C. ¹H NMR (400 MHz, CDCl₃): 4.02 (3H, s, NCH₃), 7.00 [1H, s, 5-H (pp)], 7.50–7.64 [6H, m, 2 × 3-5-H (2-Ph, 4-Ph)], 7.75 [2H, dm, J = 8 Hz, 2,6-H (6-Ph)], 7.84 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 8.32 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.74 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.2, 101.8, 112.2, 114.0, 118.5, 127.9, 128.2, 128.4, 128.8, 129.0, 129.4, 129.8, 130.2, 132.6, 132.9, 138.5, 138.8, 155.0, 157.3, 158.2 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₆H₁₉N₄): 387.1603, found: 387.1604.

7-Methyl-2,4,6-triphenyl-7H-pyrrolo[2,3-d]pyrimidine (2c)

Product 2c was obtained as a yellowish solid (71 mg, 80%), mp 134–134.9 °C. ¹H NMR (400 MHz, CDCl₃): 4.00 (3H, s, NCH₃), 6.92 [1H, s, 5-H (pp)], 7.49–7.64 [11H, m, 2 × 3-5-H (2-Ph, 4-Ph), 2-6-H (6-Ph)], 8.36 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.75 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.0, 100.0, 114.2, 128.1, 128.4, 128.7, 128.76, 128.8, 129.0, 129.1, 129.5, 129.9, 131.7, 138.9, 139.2, 143.0, 154.7, 156.3, 157.5 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₅H₂₀N₃): 362.1652, found: 362.1652.

7-Methyl-6-(4-methylphenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2d)

Product 2d was obtained as a bright yellow solid (63 mg, 68%), mp 196–197.8 °C. ¹H NMR (400 MHz, CDCl₃): 2.48 (3H, s, CH₃), 3.99 (3H, s, NCH₃), 6.88 [1H, s, 5-H (pp)], 7.36 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 7.46–7.62 [8H, m, 2 × 3-5-H (2-Ph, 4-Ph), 2,6-H (6-Ph)], 8.34 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.74 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 21.4, 29.9, 99.6, 114.3, 128.0, 128.4, 128.7, 128.8, 128.98, 128.99, 129.4, 129.5, 129.8, 138.8, 139.0, 139.3, 143.2, 154.7, 156.1, 157.3 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₆H₂₂N₃): 376.1808, found: 376.1814.

6-(4-Trifluoromethylphenyl)-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2e)

Product 2e was obtained as a bright yellow solid (66 mg, 66%), mp 200–201.7 °C. Compound 3 was also isolated (7 mg, 5%). ¹H NMR (400 MHz, CDCl₃): 4.00 (3H, s, NCH₃), 6.97 [1H, s, 5-H (pp)], 7.49–7.61 [6H, m, 2 × 3-5-H (2-Ph, 4-Ph)], 7.75 [2H, dm, J = 8 Hz, 2,6-H (6-Ph)], 7.81 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 8.33 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.75 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm ¹³C NMR (100 MHz, CDCl₃): 30.1, 101.2, 114.0, 124.0 (J = 273 Hz), 125.8 (J = 4 Hz), 128.1, 128.4, 128.7, 129.0, 129.3, 129.7, 130.1, 130.7 (J = 33 Hz), 135.3, 138.7, 139.0, 141.1, 154.8, 156.9, 157.9 ppm. ¹⁹F NMR (376 MHz, CDCl₃): −62.65 (CF₃) ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₆H₁₉F₃N₃): 430.1526, found: 430.1531.

6-[4-((Dimethylamino)phenyl)]-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2f)

Product 2f was obtained as a dark yellow solid (55 mg, 56%), mp 214.4–215.5 °C. Compound 3 was also isolated (7 mg, 5%). ¹H NMR (400 MHz, CDCl₃): 3.07 (6H, s, N(CH₃)₂), 4.00 (3H, s, NCH₃), 6.83–6.86 [3H, m, 5-H (pp), 3,5-H (6-Ph)], 7.49–7.61 [8H, m, 2 × 3-5-H (2-Ph, 4-Ph), 2,6-H (6-Ph)], 8.37 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.75 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.0, 40.4, 98.3, 112.1, 114.6, 119.1, 128.0, 128.4, 128.6, 129.0, 129.3, 129.6, 130.0, 139.2, 139.4, 144.0, 150.6, 154.7, 155.3, 156.8 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₇H₂₅N₄): 405.2074, found: 405.2077.

6-(4-Fluorophenyl)-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2g)

Product 2g was obtained as a yellowish solid (67 mg, 72%), mp 150–151.4 °C. ¹H NMR (400 MHz, CDCl₃): 3.98 (3H, s, NCH₃), 6.88 [1H, s, 5-H (pp)], 7.23–7.27 [2H, m, 3,5-H (6-Ph)], 7.48–7.62 [8H, m, 2 × 3-5-H (2-Ph, 4-Ph), 2,6-H (6-Ph)], 8.34 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.74 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 29.9, 100.1, 114.1, 115.9 [d, J = 22 Hz, 3,5-C (6-Ph)], 127.84 [d, J = 4 Hz, 1-C(6-Ph)], 128.1, 128.4, 128.7, 129.0, 129.6, 129.9, 130.9 [d, J = 8 Hz, 2,6-C (6-Ph)], 138.8, 139.1, 141.9, 154.6, 156.4, 157.6, 163.1 [d, J = 247 Hz, 4-C (6-Ph)] ppm. ¹⁹F NMR (376 MHz, CDCl₃): −112.17 (F) ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₅H₁₉FN₃): 380.1558, found: 380.1559.

6-(Biphenyl-4-yl)-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2h)

Product 2h was obtained as a yellowish solid (76 mg, 70%), mp 242.3–244 °C. ¹H NMR (400 MHz, CDCl₃): 4.06 (3H, s, NCH₃), 6.97 [1H, s, 5-H (pp)], 7.40–7.79 [15H, m, 2 × 3-5-H (2-Ph, 4-Ph), 2,3,5,6,2′-6′-H (6-biPh)], 8.36 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.75 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.1, 100.1, 114.3, 127.1, 127.5, 127.8, 128.1, 128.4, 128.7, 128.9, 129.0, 129.4, 129.5, 129.9, 130.6, 138.9, 139.2, 140.3, 141.6, 142.7, 154.8, 156.3, 157.5 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₃₁H₂₄N₃): 438.1965, found: 438.1970.

6-[4-(9H-Carbazol-9-yl)phenyl]-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2i)

Product 2i was obtained as a yellowish solid (107 mg, 83%), mp 258.5–259.8 °C. ¹H NMR (400 MHz, CDCl₃): 4.12 (3H, s, NCH₃), 7.04 [1H, s, 5-H (pp)], 7.37–7.64 [12H, m, 2 × 3-5-H (2-Ph, 4-Ph), 1-3, 6-8-H (6-carb.)], 7.77 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 7.87 [2H, dm, J = 8 Hz, 2,6-H (6-Ph)], 8.21 [2H, dm, J = 8 Hz, 4,5-H (6-carb.)], 8.39 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.78 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.2, 100.6, 109.8, 114.2, 120.3, 120.5, 123.7, 126.1, 127.2, 128.1, 128.4, 128.8, 129.0, 129.6, 130.0, 130.5, 130.6, 138.2, 138.8, 139.1, 140.6, 142.0, 154.9, 156.6, 157.7 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₃₇H₂₇N₄): 527.2230, found: 527.2242.

7-Methyl-6-(4-nitrophenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2j)

Product 2j was obtained as an orange solid (52 mg, 52%), mp 263.1–264.5 °C. Compound 4 was also isolated (4 mg, 3%). ¹H NMR (400 MHz, CDCl₃): 4.05 (3H, s, NCH₃), 7.05 [1H, s, 5-H (pp)], 7.52–7.62 [6H, m, 2 × 3-5-H (2-Ph, 4-Ph)], 7.82 [2H, dm, J = 8 Hz, 2,6-H (6-Ph)], 8.33 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.41[2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 8.74 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.3, 102.3, 114.0, 124.1, 128.2, 128.4, 128.8, 129.0, 129.5, 129.9, 130.2, 138.1, 138.5, 138.8, 140.1, 147.6, 155.1, 157.5, 158.4 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₅H₁₉N₄O₂): 407.1503, found: 407.1506.

7-Methyl-6-(2-methylphenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2k)

Product 2k was obtained as a yellowish oil (73 mg, 79%). ¹H NMR (400 MHz, CDCl₃): 2.30 (3H, s, CH₃), 3.76 (3H, s, NCH₃), 6.84 [1H, s, 5-H (pp)], 7.36–7.64 [10H, m, 2 × 3-5-H (2-Ph, 4-Ph), 3-6-H (6-Ph)], 8.39 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.79 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 20.0, 29.2, 100.1, 114.2, 125.9, 128.1, 128.4, 128.7, 129.1, 129.4, 129.5, 129.9, 130.4, 130.8, 131.4, 137.9, 139.0, 139.3, 142.3, 153.9, 156.2, 157.4 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₆H₂₂N₃): 376.1808, found: 376.1811.

7-Methyl-6-(2,6-dimethylphenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2l)

Product 2l was obtained as a colorless oil (48 mg, 50%). Compound 3 was also isolated (10 mg, 7%). ¹H NMR (400 MHz, CDCl₃): 2.16 (6H, s, 2 × CH₃), 3.67 (3H, s, NCH₃), 6.77 [1H, s, 5-H (pp)], 7.22–7.34 [3H, m, 3-5-H (6-Ph)], 7.51–7.61 [6H, m, 2 × 3-5-H (2-Ph. 4-Ph)], 8.38 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.76 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 20.4, 28.6, 99.5, 114.3, 127.5, 128.0, 128.4, 128.7, 129.1, 129.2, 129.5, 129.8, 131.1, 138.4, 139.0, 139.2, 141.0, 153.7, 156.0, 157.1 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₇H₂₄N₃): 390.1965, found: 390.1972.

6-[2,4-Di(trifluoromethyl)phenyl]-7-methyl-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2m)

Product 2m was obtained as a colorless solid (79 mg, 65%), mp 189–190.8 °C. ¹H NMR (400 MHz, CDCl₃): 3.74 (3H, s, NCH₃), 6.93 [1H, s, 5-H (pp)], 7.50–7.62 [6H, m, 2 × 3-5-H (2-Ph, 4-Ph)], 7.69 [1H, d, J = 8 Hz, 5-H (6-Ph)], 7.99 [1H, d, J = 8 Hz, 6-H (6-Ph)], 8.16 [1H, s, 3-H (6-Ph)], 8.32 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.75 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 29.3, 102.5, 113.6, 122.8 (J = 273 Hz), 123.1 (J = 271 Hz), 123.79 (J = 4 Hz), 123.84 (J = 4 Hz), 128.1, 128.41, 128.42, 128.8, 129.0, 129.8, 130.1, 131.8 (J = 31 Hz), 132.0 (J = 34 Hz), 133.76, 133.77, 134.3, 136.3, 138.6, 138.9, 153.8, 157.3, 158.2 ppm. ¹⁹F NMR (376 MHz, CDCl₃): −59.11 (CF₃), −63.00 (CF₃) ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₇H₁₈F₆N₃): 498.1399, found: 498.1396.

7-Methyl-6-[(4-diphenylamino)phenyl]-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2n)

Product 2n was obtained as a bright yellow film (100 mg, 77%). ¹H NMR (400 MHz, CDCl₃): 4.03 (3H, s, NCH₃), 6.88 [1H, s, 5-H (pp)], 7.12–7.22 [8H, m, 3,5-H (6-Ph), 2 × 2′,4′,6′-H (NPh₂)], 7.32–7.36 [4H, m, 2 × 3′,5′-H (NPh₂)], 7.46–7.62 [8H, m, 2,6-H (6-Ph), 2 × 3-5-H (2-Ph, 4-Ph)], 8.35 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.74 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.1, 99.3, 114.4, 122.5, 123.7, 124.7, 125.0, 125.1, 128.0, 128.4, 128.7, 129.0, 129.4, 129.5, 129.8, 139.0, 139.3, 143.1, 147.3, 148.4, 154.7, 155.9, 157.2 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₃₇H₂₉N₄): 529.2387, found: 529.2385.

7-Methyl-6-(naphthalen-2-yl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (2o)

Product 2o was obtained as a yellow solid (63 mg, 62%), mp 185.5–187 °C. ¹H NMR (400 MHz, CDCl₃): 4.06 (3H, s, NCH₃), 7.02 [1H, s, 5-H (pp)], 7.50–7.62 [8H, m, 2 × 3-5-H (2-Ph, 4-Ph), 4,5-H (6-naph)], 7.73 [1H, dd, J = 8 Hz, 8-H (6-naph)], 7.95–7.98 [2H, m, 3,6-H (6-naph)], 8.01 [1H, d, J = 8 Hz, 7-H (6-naph)], 8.10 [1H, s, 2-H (6-naph)], 8.38 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.77 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.2, 100.4, 114.3, 126.5, 126.86, 126.9, 127.9, 128.1, 128.3, 128.4, 128.41, 128.5, 128.7, 129.0, 129.1, 129.6, 129.9, 133.1, 133.2, 138.9, 139.2, 143.1, 154.8, 156.4, 157.5 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₉H₂₂N₃): 412.1808, found: 412.1812.

6-(2,4-Di(trifluoromethyl)phenyl)-2,4-di(4-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (2p)

Compound 2p was synthesized by the general procedure for C–H arylation, starting from 2,4-di(4-methoxyphenyl)-7-methylpyrrolo[2,3-d]pyrimidine (1b) (70 mg, 0.20 mmol). After 72 h (170 °C) product 2p was obtained as a colorless solid (87 mg, 77%), mp 185.5–186.2 °C. ¹H NMR (400 MHz, CDCl₃): 3.71 (3H, s, NCH₃), 3.93 (6H, s, 2 × OCH₃), 6.88 [1H, s, 5-H (pp)], 7.07 [2H, d, J = 8 Hz, 3,5-H (2-Ph)], 7.11 [2H, d, J = 8 Hz, 3,5-H (4-Ph)], 7.68 [1H, d, J = 8 Hz, 5-H (6-Ph)], 7.98 [1H, d, J = 8 Hz, 6-H (6-Ph)], 8.15 [1H, s, 3-H (6-Ph)], 8.29 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.68 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 29.2, 55.4, 55.43, 102.6, 112.6, 112.9, 113.7, 114.3, 122.9 (J = 272 Hz), 123.2 (J = 272 Hz), 123.77 (J = 4 Hz), 123.8 (J = 4 Hz), 124.2, 124.5, 128.3, 129.6, 130.5, 131.3, 131.7 (J = 34 Hz), 131.8, 131.9 (J = 34 Hz), 133.8, 133.81, 134.6, 135.4153.9, 156.8, 158.1, 161.1, 161.3 ppm. ¹⁹F NMR (376 MHz, CDCl₃): −59.07 (CF₃), −62.97 (CF₃) ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₉H₂₂F₆N₃O₂): 558.1611, found: 558.1613.

6-[4-((Dimethylamino)phenyl)]-2,4-di(4-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (2q)

Compound 2q was synthesized by the general procedure for C–H arylation, starting from 2,4-di(4-methoxyphenyl)-7-methylpyrrolo[2,3-d]pyrimidine (1b) (70 mg, 0.20 mmol). After 72 h (170 °C) product 2q was obtained as a yellow film (72 mg, 77%). ¹H NMR (400 MHz, CDCl₃): 3.07 (6H, s, N(CH₃)₂), 3.92 (3H, s, OCH₃), 3.94 (3H, s, OCH₃), 3.97 (3H, s, NCH₃), 6.78 [1H, s, 5-H (pp)], 6.86 [2H, d, J = 8 Hz, 3,5-H (6-Ph)], 7.06 [2H, d, J = 8 Hz, 3,5-H (2-Ph)], 7.11 [2H, d, J = 8 Hz, 3,5-H (4-Ph)], 7.50 [2H, d, J = 8 Hz, 3,5-H (6-Ph)], 8.33 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.67 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 29.9, 40.4, 55.4, 55.42, 98.4, 112.1, 113.5, 113.6, 114.0, 119.3, 129.38, 129.9, 130.4, 131.9, 132.3, 143.3, 150.5, 154.6, 154.9, 156.7, 160.8, 160.9 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₂₉H₂₉N₄O₂): 465.2285, found: 465.2289.

6-[4-(9H-Carbazol-9-yl)phenyl]-2,4-di(4-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (2r)

Compound 2r was synthesized by the general procedure for C–H arylation, starting from 2,4-di(4-methoxyphenyl)-7-methylpyrrolo[2,3-d]pyrimidine (1b) (70 mg, 0.20 mmol). After 72 h (170 °C) product 2r was obtained as a yellow solid (83 mg, 70%), mp 265.2–266.6 °C. ¹H NMR (400 MHz, CDCl₃): 3.94 (3H, s, OCH₃), 3.95 (3H, s, OCH₃), 4.10 (3H, s, NCH₃), 7.01 [1H, s, 5-H (pp)], 7.08 [2H, d, J = 8 Hz, 3,5-H (4-Ph)], 7.14 [2H, d, J = 8 Hz, 3,5-H (2-Ph)], 7.34–7.38 [2H, m, 3,6-H (6-carb.)], 7.47–7.50 [2H, m, 2,7-H (6-carb.)], 7.77 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 7.86 [2H, dm, J = 8 Hz, 2,6-H (6-Ph)], 8.21 [2H, dm, J = 8 Hz, 4,5-H (6-carb.)], 8.37 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.71 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.1, 55.4, 55.45, 100.7, 109.8, 113.2, 113.7, 114.1, 120.3, 120.5, 123.6, 126.1, 127.2, 129.6, 130.4, 130.5, 130.5, 130.8, 131.6, 132.0, 138.1, 140.6, 141.3, 156.1, 161.0, 161.2 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₃₉H₃₁N₄O₂): 587.2442, found: 587.2444.

2,4-Di(4-(9H-carbazol-9-yl)phenyl)-7-methyl-6-(4-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidine (2s)

Compound 2s was synthesized by the general procedure for C–H arylation, starting from 2,4-di(4-(9H-carbazol-9-yl)phenyl)-7-methylpyrrolo[2,3-d]pyrimidine (1c) (70 mg, 0.13 mmol). After 70 h (170 °C) product 2s was obtained as a yellowish solid (47 mg, 50%), mp 305–306 °C. ¹H NMR (400 MHz, CDCl₃): 2.52 (3H, s, CH₃), 4.07 (3H, s, NCH₃), 7.03 [1H, s, 5-H (pp)], 7.34–7.52 [10H, m, 3,5-H (6-Ph), 2 × 2,7-H (2-carb., 4-carb.), 2 × 3,6-H (2-carb., 4-carb.)], 7.58–7.62 [6H, m, 2,6-H (6-Ph), 2 × 1,8-H (2-carb., 4-carb.)], 7.80 [2H, dm, J = 8 Hz, 3,5-H (2-Ph)], 7.86 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 8.22 [4H, m, 2 × 4,5-H (2-carb., 4-carb.)], 8.65 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 9.02 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 21.4, 30.1, 99.6, 109.9, 110.0, 114.4, 120.0, 120.2, 120.35, 120.42, 123.5, 123.6, 126.0, 126.1, 126.9, 127.1, 128.6, 129.0, 129.6, 129.62, 130.5, 137.8, 138.2, 138.8, 139.1, 139.3, 140.7, 140.8, 143.9, 154.8, 155.1, 156.7 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₅₀H₃₆N₅): 706.2965, found: 706.2961.

7,7′-Dimethyl-2,2′4,4′-tetraphenyl-7H,7′H-5,5′bipyrrolo[2,3-d]pyrimidine (3)

Yellow solid, mp 269–270 °C. ¹H NMR (400 MHz, CDCl₃): 4.00 (3H, s, NCH₃), 7.13 [1H, s, 6-H (pp)], 7.55–7.64 [6H, m, 2 × 3-5-H (2-Ph, 4-Ph)], 8.36 [2H, dm, J = 8 Hz, 2,6-H (4-Ph)], 8.76 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 29.9, 103.6, 113.8, 129.2, 128.5, 128.9, 129.1, 129.9, 130.2, 131.9, 138.5, 138.8, 154.4, 157.5, 158.5 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₃₈H₂₉N₆): 569.2448, found: 569.2462.

7-Methyl-5,6-di(4-nitrophenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine (4)

Yellow solid, mp 274.5–275 °C. ¹H NMR (400 MHz, CDCl₃): 3.96 (3H, s, NCH₃), 6.90 [2H, dm, J = 8 Hz, 2,6-H (5-Ph)], 7.11–7.15 [2H, m, 2 × 4-H (2-Ph, 4-Ph)], 7.37–7.55 [8H, m, 2,6-H (6-Ph), 3,5-H (2-Ph), 2,3,5,6-H (4-Ph)], 7.82 [2H, dm, J = 8 Hz, 3,5-H (5-Ph)], 8.29 [2H, dm, J = 8 Hz, 3,5-H (6-Ph)], 8.73 [2H, dm, J = 8 Hz, 2,6-H (2-Ph)] ppm. ¹³C NMR (100 MHz, CDCl₃): 30.1, 112.7, 114.0, 122.9, 124.0, 127.6, 128.3, 128.5, 129.4, 129.6, 130.2, 131.2, 131.8, 136.6, 137.2, 137.5, 138.3, 140.6, 146.1, 148.0, 153.9, 158.6, 160.0 ppm. HRMS-ESI: m/z calcd. for MH⁺ (C₃₁H₂₂N₅O₄): 528.1666, found: 528.1675.

Acknowledgements

The research was funded by a grant (no. MIP-027/2013) from the Research Council of Lithuania.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra07088g

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