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

Isopropyl chloroformate (1M in toluene, 1.076 mL, 1.076 mmol) and then N-methyl morpholine (0.118 mL, 1.076 mmol) were added to a stirred mixture of 2-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanoic acid (0.233 g, 0.978 mmol) in dimethylformamide (4.7 mL) under nitrogen at −10° C. to −15° C. The reaction mixture was stirred for one hour at this temperature then ammonia (0.5 M solution in 1,4-dioxane, 3.91 mL, 1.956 mmol) and triethylamine (0.136 mL, 0.978 mmol) in dimethylformamide (0.1 mL) were added. The reaction mixture was allowed to stir at −10° C. to −15° C. for one further hour then allowed to warm to room temperature. After 64 hours, ether (10 mL) was added and the precipitate was washed with ether (10 mL), acetonitrile (10 mL) and water (4×10 mL) to afford the title compound. Yield 105 mg, 0.443 mmol, 45%. LCMS (ES+), m/z 238 (M+H)+ at the solvent front. 1H NMR (400 MHz, d6-DMSO) δ: 8.88 (1H, s), 7.84 (1H, br s), 7.72 (1H, br s), 7.70 (1H, br s), 7.44 (1H, br s) 4.88 (2H, s).

1. stirringto stir at −10° C. to −15° C. for one further hour
2. waitAfter 64 hours
3. washthe precipitate was washed with ether (10 mL), acetonitrile (10 mL) and water (4×10 mL)

ORD record

ord-ad8068b697664c2d8d6e6b1d9d90185f

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450479B2