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

Isobutyl chloroformate (1 M in toluene, 0.218 mL, 0.218 mmol) then N-methyl morpholine (0.024 mL, 0.218 mmol) were added to a stirred mixture of 3-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)propanoic acid (0.05 g, 0.198 mmol) in dimethylformamide (1.25 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, 792 μL, 0.396 mmol) and triethylamine (27.5 μL, 0.198 mmol) in dimethylformamide (0.1 mL) were added. The reaction mixture was stirred at −10° C. to −15° C. for one further hour then allowed to warm to room temperature. After 16 hours, ether (2 mL) was added and the resulting precipitate was washed with ether (10 mL), acetonitrile (10 mL) and water to afford the title compound as a white solid. Yield 12 mg, 0.048 mmol, 24%. LCMS (ES+), m/z 252 (M+H)+ at the solvent front. 1H NMR (400 MHz, d6-DMSO) δ: 8.82 (1H, s), 7.77 (1H, br s), 7.65 (1H, br s), 7.45 (1H, br s), 6.92 (1H, br s) 4.45 (2H, t), 2.64 (2H, t).

1. stirringThe reaction mixture was stirred at −10° C. to −15° C. for one further hour
2. waitAfter 16 hours
3. washthe resulting precipitate was washed with ether (10 mL), acetonitrile (10 mL) and water

ORD record

ord-bf7234aa0d094ab8a88ab36cc76a5241

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450479B2