Sodium Carbonate → 5-(2-amino-4-methoxycarbonylphenyl)-1-isobutyl-1H-imidazole-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a suspension of Pd(OAc)2 (11.2 mg, 0.05 mmol, 0.05 equiv) and PPh3 (26.2 mg, 0.1 mmol, 0.1 equiv) in DME (4 mL) were sequentially added 5-iodo-1-isobutyl-1H-imidazole-4-carbonitrile S5 (275 mg, 1 mmol, 1 equiv), 2-amino-4-methoxycarbonylphenyl-boronic acid hydrochloride salt (347 mg, 1.5 mmol, 1.5 equiv) and 1.5 M aqueous Na2CO3 (2.0 mL, 3.0 mmol, 3.0 equiv) at 25° C. The reaction was heated at 100° C. for 3 h. TLC and MS analysis indicated complete conversion of S5. The reaction was then cooled down to 25° C. and partitioned between EtOAc (50 mL) and H2O (10 mL). The aqueous layer was extracted with EtOAc (3×15 mL) and the combined organic layers were washed with saturated aqueous NaCl (20 mL), dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica gel (1/9 EtOAc/hexanes-7/3 EtOAc/hexanes, gradient) afforded the title compound (265 mg, 89%) as a light yellow foam: 1H NMR (CDCl3, 600 Hz) δ 0.71 (d, J=9.6 Hz, 3H), 0.75 (d, J=9.6 Hz, 3H), 1.75 (hept, J=9.6 Hz, 1H), 3.64-3.67 (m, 2H), 3.90 (s, 3H), 7.15 (d, J=7.8 Hz, 1H), 7.44 (d, J=7.8 Hz), 7.45 (s, 1H), 7.57 (s, 1H); 13C NMR (CDCl3, 150 Hz) δ 19.6, 19.7, 29.5, 52.3, 53.6, 117.0, 128.4, 128.5, 131.7, 131.9, 131.9, 132.0, 132.1, 133.2, 139.8, 166.5; LRMS (ESI+): calcd C16H19N4O2 [M+H]+299.2. found 299.1.

Provenance & Evidence