Hydrochloric Acid → HCID 67365100, compound

(R)-Benzyl 3-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (1.264 mmol, 525 mg) was dissolved in 37% hydrochloric acid (76 mmol, 6 mL) and stirred at room temperature. After four hours water (10 ml) was added and the mixture was washed twice with diethyl ether. The aqueous layer was concentrated under reduced pressure and coevaporated with toluene and ethanol to give 0.42 g of (R)-1-bromo-8-methyl-3-(pyrrolidin-3-yl)imidazo[1,5-a]pyrazine as hydrochloride. To 100 mg of this material in dichloromethane (5 ml) and N,N-diisopropylethylamine (1.778 mmol, 0.31 mL) were added N,N-dimethylglycine (0.534 mmol, 55.0 mg) and O-(7-azabenzotriazol-1-yl)1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.534 mmol, 203 mg) and stirred at room temperature for 16 hours. The reaction mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogencarbonate solution, brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; dichloromethane/methanol (gradient 0->35% methanol)) to give (R)-1-(3-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)pyrrolidin-1-yl)-2-(dimethylamino)ethanone (77 mg).

1. washthe mixture was washed twice with diethyl ether
2. concentrationThe aqueous layer was concentrated under reduced pressure

ORD record

ord-52581ff477154a3c9b80183834a7ab3d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658794B2