反应详情

Benzothioamide (1.37 g, 10 mmol) and benzylbromide (1.71 g, 10 mmol) in dry THF were heated to 60° C. for 2 h. After it was allowed to cool to room temperature, the reaction mixture was filtered. The desired benzyl benzimidothioate hydrobromide as a white solid (2 g, 65%) without further purification. To a solution of benzyl benzimidothioate hydrobromide (1.54 g, 5 mmol) in dry CHCl3 was added in one portion dry pyridine (5 mmol) at ambient temperature followed by ethyl 2-amino-2-cyanoacetate (0.64 g, 5 mmol). The reaction mixture was then heated to 65° C. for 2 h. After cooling to room temperature, the mixture was filtered to give the ethyl 5-amino-2-phenyl-1H-imidazole-4-carboxylate as a yellow colored solid (0.8 g, 68%). This solid (0.46 g, 2 mmol) was added with dry THF, Boc2O (0.87 g, 4 mmol), DMAP (24 mg, 0.2 mmol). The reaction was heated to 65° C. for 5 h. The solvent was evaporated in vacuo to give crude product. This crude product was then dissolved in MeOH—H2O (30 mL, 1:1) and LiOH was added in one portion. The reaction mixture was heated at 70° C. until starting material disappeared by TLC (˜4 h). The mixture was then cooled to ˜0-4° C. and 1N aq HCl was added cautiously dropwise until pH ˜5. The resulted mixture was extracted with DCM (3×20 mL). Combined organic layers were washed with brine (2×20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by prep-HPLC. The desired product 5-(tert-butoxycarbonylamino)-2-phenyl-1H-imidazole-4-carboxylic acid was obtained as white solid (0.1 g, 16%). 1H-NMR (DMSO, 500 MHz) δ (ppm): 9.01 (s, 1H), 8.05 (s, 2H), 7.35-7.42 (m, 3H), 1.45 (s, 9H); MS (ESI) m/z: 304 [M+H+].

1. filtrationthe reaction mixture was filtered
2. customThe desired benzyl benzimidothioate hydrobromide as a white solid (2 g, 65%) without further purification
3. temperatureThe reaction mixture was then heated to 65° C. for 2 h
4. temperatureAfter cooling to room temperature
5. filtrationthe mixture was filtered