Cesium carbonate → 5-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

N-(5-iodo-4-methyl-1,3-thiazol-2-yl)acetamide, Intermediate 1 (550 mg; 1.95 mmol; 1 eq.), 5-(dihydroxyboryl)-2-thiophenecarboxylic acid (335.3 mg; 1.95 mmol; 1 eq.), cesium carbonate (1397.5 mg; 4.29 mmol; 2.20 eq.), Pd(dppf)Cl2 (57.1 mg; 0.08 mmol; 0.04 eq.) are put in a microwave reactor, followed by DMF (8 ml) and water (4 ml). The reaction mixture is flushed with argon and is heated under microwave action for 10 min at 150° C. It is filtered through a paper filter, diluted with HCl 1N solution (10 ml) and the desired product is extracted with EtOAc. Combined organic layer is dried over MgSO4, filtered and evaporated. The crude product is purified by preparative HPLC, affording Compound (4) as white-off solid (125 mg; 22.7%). 1H NMR (DMSO-d6) δ 2.14 (s, 3H), 2.44 (s, 3H), 7.21 (d, J=3.8 Hz, 1H), 7.67 (d, J=3.8 Hz, 1H), 12.30 (s, 1H), 13.15 (br s, 1H). M−(ESI): 281; M+(ESI): 283. HPLC, Rt: 2.54 min (purity: 99.9%).

Provenance & Evidence