Paper
Methyl 7-cyano-2,6-diphenyl-1H-pyrrolo[1,2-a]imidazole-5-
Organic & Biomolecular Chemistry
Methyl
7-cyano-2-(4-methoxyphenyl)-6-phenyl-1H-pyrrolo
carboxylate (10a). Beige solid (119 mg, yield 70%). Mp: [1,2-a]imidazole-5-carboxylate (10g). Colorless solid (74 mg,
278–280 °C (Et2O–acetone). 1H NMR (400 MHz, DMSO-d6) δ yield 40%). Mp: 257–258 °C (Et2O). 1H NMR (400 MHz, DMSO-
13.13 (s, 1H), 8.28 (d, J4 = 1.6 Hz, 1H), 7.92–7.85 (m, 2H), d6) δ 12.97 (s, 1H), 8.12 (s, 1H), 7.81–7.76 (m, 2H), 7.53–7.49
7.53–7.40 (m, 8H), 3.70 (s, 3H). 13C NMR (100 MHz, DMSO-d6) (m, 2H), 7.46–7.40 (m, 3H), 7.08–7.02 (m, 2H), 3.81 (s, 3H),
δ 159.9, 139.9, 138.7, 133.0, 132.3, 130.0, 129.0, 128.5, 128.4, 3.69 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 159.9, 159.4,
128.1, 127.7, 124.9, 116.02, 107.0, 105.1, 68.2, 50.9. HRMS-ESI 139.7, 138.3, 133.1, 132.4, 130.0, 128.0, 127.6, 126.4, 121.0,
[M − H]− calcd for C21H14N3O2−, 340.1092; found, 340.1073.
Methyl 7-cyano-2-(naphthalen-2-yl)-6-phenyl-1H-pyrrolo[1,2- calcd for C22H17N3NaO3 , 394.1162; found, 394.1163.
116.1, 114.4, 105.8, 105.0, 68.1, 55.2, 50.8. HRMS-ESI [M + Na]+
+
a]imidazole-5-carboxylate (10b). Beige solid (164 mg, yield
Methyl
7-cyano-6-phenyl-2-(p-tolyl)-1H-pyrrolo[1,2-a]imid-
84%). Mp: 309–310 °C (Et2O–acetone). 1H NMR (400 MHz, azole-5-carboxylate (10h). Colorless solid (37 mg, yield 21%).
1
DMSO-d6) δ 13.25 (s, 1H), 8.42–8.35 (m, 2H), 8.02–7.98 (m, Mp: 271–272 °C (Et2O). H NMR (400 MHz, DMSO-d6) δ 13.06
2H), 7.96–7.90 (m, 2H), 7.60–7.52 (m, 4H), 7.49–7.41 (m, 3H), (s, 1H), 8.22 (s, 1H), 7.80–7.73 (m, 2H), 7.54–7.41 (m, 5H),
3.71 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 159.9, 140.1, 7.34–7.28 (m, 2H), 3.70 (s, 3H), 2.35 (s, 3H). 13C NMR
138.7, 133.0, 132.9, 132.6, 132.3, 130.0, 128.6, 128.1, 127.9, (100 MHz, DMSO-d6) δ 159.9, 139.8, 138.5, 138.0, 133.1, 132.4,
127.7, 126.9, 126.5, 126.0, 123.3, 123.0, 116.0, 107.6, 105.2, 130.0, 129.5, 128.1, 127.7, 125.7, 124.9, 116.0, 106.5, 105.0,
H]+ calcd for C25H18N3O2 , 68.1, 50.8, 20.79. HRMS-ESI [M
+
Na]+ calcd for
+
68.2, 50.9. HRMS-ESI [M
392.1394; found, 392.1394.
+
+
C22H17N3NaO2 , 378.1213; found, 378.1215.
Methyl 2-(4-bromophenyl)-7-cyano-6-phenyl-1H-pyrrolo[1,2-
a]imidazole-5-carboxylate (10c). Brown solid (147 mg, yield
70%). Mp: 324–325 °C (Et2O–acetone). 1H NMR (400 MHz,
DMSO-d6) δ 13.16 (s, 1H), 8.32 (s, 1H), 7.88–7.79 (m, 2H),
7.73–7.65 (m, 2H), 7.54–7.48 (m, 2H), 7.48–7.40 (m, 3H), 3.69
(s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 159.8, 140.0, 138.8,
132.3, 132.0, 131.9, 129.9, 128.1, 127.8, 127.7, 126.9, 121.4,
115.9, 107.6, 105.1, 68.1, 50.9. HRMS-ESI − H]− calcd for
C21H1381BrN3O2−, 420.0176; found, 420.0168.
Procedure for the preparation of pyrroloimidazole 12
A suspension of pyrrole 2b (120 mg, 0.5 mmol), 2-bromo-1-
phenylethanone (249 mg, 1.25 mmol) and K2CO3 (207 mg,
1.5 mmol) in DMF (3 mL) was stirred for 72 h at ambient
temperature. The reaction mixture was concentrated in vacuo,
and the residue was purified by column chromatography on
silica gel (EtOAc–hexane from 1 : 20 to 1 : 3) to give methyl
7-cyano-1-(2-oxo-2-phenylethyl)-2,6-diphenyl-1H-pyrrolo[1,2-a]
imidazole-5-carboxylate 12. Colorless solid (96 mg, yield 42%).
Methyl 7-cyano-2-(4-fluorophenyl)-6-phenyl-1H-pyrrolo[1,2-a]
imidazole-5-carboxylate (10d). Grey solid (140 mg, yield 78%).
1
Mp: 180–181 °C (Et2O). H NMR (400 MHz, CDCl3) δ 7.98–7.93
1
Mp: 280–282 °C (Et2O–acetone). H NMR (400 MHz, DMSO-d6)
(m, 2H), 7.91 (s, 1H), 7.67–7.62 (m, 1H), 7.61–7.56 (m, 2H),
7.53–7.41 (m, 10H), 5.56 (s, 2H), 3.79 (s, 3H). 13C NMR
(100 MHz, CDCl3) 191.7, 161.1, 140.9, 139.5, 135.3, 134.5,
133.7, 132.3, 130.2, 129.8, 129.4, 129.2, 129.1, 128.3, 128.2,
127.8, 127.3, 115.8, 109.4, 106.5, 69.3, 51.1, 50.4. HRMS-ESI [M
δ: 13.16 (s, 1H), 8.32 (s, 1H), 7.88–7.79 (m, 2H), 7.73–7.65 (m,
2H), 7.54–7.48 (m, 2H), 7.48–7.40 (m, 3H), 3.69 (s, 3H). 13C
NMR (100 MHz, DMSO-d6) δ 162.0 (d, J = 246.2 Hz), 159.9,
139.3 (d, J = 129.0 Hz), 132.3, 132.2, 130.0, 128.1, 127.7, 127.2
(d, J = 8.4 Hz), 125.2 (d, J = 3.0 Hz), 116.1, 116.0, 115.9, 107.0,
+
+ Na]+ calcd for C29H21N3NaO3 , 482.1475; found, 482.1473.
+
105.1, 68.1, 50.9. HRMS-ESI [M + H]+ calcd for C21H15FN3O2
360.1143; found, 360.1160.
,
General procedure for the preparation of pyrrolopyrimidine 13
Methyl 2-(2-bromophenyl)-7-cyano-6-phenyl-1H-pyrrolo[1,2-
a]imidazole-5-carboxylate (10e). Brown solid (147 mg, yield A solution of pyrrole 2 (1 mmol) in formamide (5 mL) was
70%). Mp: 238–239 °C (Et2O–acetone). 1H NMR (400 MHz, heated at 180 °C for 1 h. After the reaction was completed, the
DMSO-d6) δ 13.13 (s, 1H), 8.13 (s, 1H), 7.87–7.80 (m, 1H), resulting mixture was cooled to rt. The precipitate formed was
7.74–7.69 (m, 1H), 7.58–7.51 (m, 3H), 7.49–7.40 (m, 4H), 3.67 filtered off, washed with formamide (3 mL) and then recrystal-
(s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 160.0, 139.3, 138.8, lized from the DMSO–H2O mixture (1 : 2).
133.6, 132.3, 131.6, 130.9, 130.8, 129.9, 129.3, 128.1, 128.0,
Methyl 4-amino-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-car-
127.7, 121.8, 115.9, 109.7, 104.9, 68.0, 50.9. HRMS-ESI boxylate (13a). Grey solid (148 mg, yield 55%). Mp: 285–286 °C
[M + Na]+ calcd for C21H1479BrN3NaO2 , 442.0162; found, (dec.). 1H NMR (400 MHz, DMSO-d6) δ 12.48 (s, 1H), 8.20 (s,
+
442.0167.
1H), 7.53–7.39 (m, 5H), 3.64 (s, 3H). 13C NMR (100 MHz,
Methyl 2-(2-chlorophenyl)-7-cyano-6-phenyl-1H-pyrrolo[1,2- DMSO-d6) δ 160.9, 158.5, 154.7, 150.2, 133.6, 129.9, 128.2,
a]imidazole-5-carboxylate (10f). Colorless solid (115 mg, yield 127.9, 122.3, 119.9, 102.1, 51.4. HRMS-ESI [M + H]+ calcd for
61%). Mp: 253–254 °C (Et2O–acetone). 1H NMR (400 MHz, C14H13N4O2 , 269.1033; found, 269.1031.
+
DMSO-d6) δ 13.15 (s, 1H), 8.17 (s, 1H), 7.81–7.76 (m, 1H),
Methyl 4-amino-5-(4-bromophenyl)-7H-pyrrolo[2,3-d]pyrimi-
7.68–7.63 (m, 1H), 7.54–7.42 (m, 7H) 3.67 (s, 3H). 13C NMR dine-6-carboxylate (13b). Grey solid (174 mg, yield 50%). Mp:
(100 MHz, DMSO-d6) δ 160.0, 139.4, 138.9, 132.3, 131.1, 130.5, 340–343 °C (dec.). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s,
130.5, 130.3, 129.9, 129.4, 128.2, 127.7, 127.6, 127.1, 115.9, 1H), 7.77–7.50 (m, 2H), 7.50–7.23 (m, 2H), 6.17 (s, 2H), 3.61 (s,
110.0, 104.9, 68.1, 50.9. HRMS-ESI [M + Na]+ calcd for 3H). 13C NMR (100 MHz, DMSO-d6) δ 160.8, 158.5, 154.7,
+
C21H1435ClN3NaO2 , 398.0667; found, 398.0657.
150.3, 132.7, 132.1, 131.1, 121.3, 121.0, 120.1, 101.8, 51.5.
1982 | Org. Biomol. Chem., 2021, 19, 1976–1984
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