Ammonium Hydroxide → HCID 178476587, compound

Temperature

70 °C

To (cis)-4-((3-chloropyrazin-2-yl)methylcarbamoyl)cyclohexyl acetate (52.9 mmol, 16.5 g) in acetonitrile (150 ml) were added dropwise subsequently phosphorus oxychloride (159 mmol, 14.80 ml) and N,N-dimethylformamide (2.65 mmol, 0.206 ml). After addition the reaction mixture was stirred at 70° C. for one hour. The reaction mixture was cooled to room temperature and added dropwise to a mixture of 25% ammonium hydroxide (125 ml) and crushed ice (350 ml). This mixture was stirred for 30 minutes at room temperature and the off white solid was isolated by filteration and rinsed with water. The solids were dissolved in dichloromethane (200 ml) and washed with water (50 ml) and brine, dried (MgSO4), and concentrated in vacuo to give (cis)-4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclohexyl acetate (10.9 g). A second crop of material was obtained by extraction of the filtrate twice using dichloromethane/methanol (10/1, 275 mL). The organic layers were combined and washed with brine, dried (MgSO4) and concentrated in vacuo to give an additional amount of (cis)-4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclohexyl acetate (3.2 g).

1. additionAfter addition the reaction mixture
2. temperatureThe reaction mixture was cooled to room temperature
3. stirringThis mixture was stirred for 30 minutes at room temperature
4. customthe off white solid was isolated by filteration
5. washrinsed with water
6. dissolutionThe solids were dissolved in dichloromethane (200 ml)
7. washwashed with water (50 ml) and brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo

ORD record

ord-afeb0f5703b1422593f3445d73a082cf

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658794B2