反应详情

At RT, to a solution of 2-bromothiazole-4-carboxylic acid (Synthonix, 600 mg, 2.88 mmol) in 8 mL of THF and 2 mL of DMF was added HATU (Aldrich, 1.2 g, 3.17 mmol). The mixture was stirred for 30 min, and cyclopropanamine (0.3 mL, 4.33 mmol) was added followed by Et3N (0.4 mL, 2.88 mmol). After the reaction mixture was stirred for 1 h at RT, additional HATU (150 mg) was added and the mixture stirred for another 1 h. It was diluted with 100 mL of EtOAc, washed sequentially with 5 mL of 1 N NaOH, 5 mL of water and 5 ml of brine. The EtOAc layer was concentrated and the residue was purified on a silica gel column (25-50% EtoAc in hexanes) to give 2-bromo-N-cyclopropylthiazole-4-carboxamide (300 mg, 42% yield) as an off white crystalline solid. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.50 (1H, m), 8.28 (1H, s), 2.87 (1H, m), 0.67 (4H, m). MS (ESI, pos. ion) m/z: 246.9/248.9 (M+1).

1. stirringAfter the reaction mixture was stirred for 1 h at RT
2. stirringthe mixture stirred for another 1 h
3. washwashed sequentially with 5 mL of 1 N NaOH, 5 mL of water and 5 ml of brine
4. concentrationThe EtOAc layer was concentrated
5. customthe residue was purified on a silica gel column (25-50% EtoAc in hexanes)