Isopropyl chloroformate → N,N-Dimethyl (8-Carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide

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Reaction Steps

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, dimethylamine hydrochloride (0.171 g, 2.100 mmol) and 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 40 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) and preparative HPLC to furnish the title compound. Yield: 23 mg, 0.082 mmol, 8%. LCMS (ES+) m/z 266 (M+H)+ at 0.80 minutes. 1H NMR (400 MHz, d6-DMSO) δ: 8.89 (1H, s), 7.86 (1H, br s), 7.72 (1H, bs), 5.33 (2H, s), 3.10 (3H, s), 2.86 (3H, s).

Provenance & Evidence