反应详情

Isopropyl chloroformate (1 M in toluene, 1.155 mL, 1.155 mmol) then N-methyl morpholine (0.127 mL, 1.155 mmol) were added to a stirred solution of 2-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanoic acid (0.25 g, 1.050 mmol) in dimethylformamide (1.34 mL) under nitrogen at −10° C. to −15° C. After 1 hour, methylamine hydrochloride (142 mg, 2.100 mmol) then triethylamine (0.292 mL, 2.100 mmol) in dimethylformamide (0.1 mL) were added. The reaction mixture was stirred at −10° C. to −15° C. for one hour then allowed to warm to room temperature. After 16 hours, ether (5 mL) was added and the resulting precipitate was washed with ether (2×5 mL), acetonitrile (2×5 mL), dichloromethane (2×5 mL) and ether (2×5 mL), then purified by flash column chromatography (SiO2, 9:1 acetonitrile/dichloromethane), recrystallized from acetonitrile and triturated with ether to furnish the desired product as a pale pink solid. Yield: 82 mg, 0.33 mmol, 31%. LCMS (ES+) m/z 252 (M+H)+ at solvent front. 1H NMR (400 MHz, d6-DMSO) δ: 8.86 (1H, s), 8.14 (1H, br q), 7.83 (1H, br s), 7.69 (1H, bs), 4.89 (2H, s), 2.60 (3H, d).

1. waitAfter 16 hours
2. washthe resulting precipitate was washed with ether (2×5 mL), acetonitrile (2×5 mL), dichloromethane (2×5 mL) and ether (2×5 mL)
3. custompurified by flash column chromatography (SiO2, 9:1 acetonitrile/dichloromethane)
4. customrecrystallized from acetonitrile
5. customtriturated with ether