Carbamate → (3R,4R)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methyl-N-(pyrimidin-4-yl)piperidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

To solution of 4-aminopyrimidine (0.04 g, 0.43 mmol), TEA (0.07 mL, 0.47 mmol) and DMAP (0.006 g, 0.05 mmol), in MeCN (1 mL) at about 0° C. was added phenyl chloroformate (0.05 mL, 0.41 mmol). The reaction mixture was warmed to ambient temperature and stirred for about 3 h. To the reaction mixture was added water (2 mL) and Et2O (5 mL). The organic layer was separated, washed with water (2 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure to provide the crude carbamate. The carbamate was dissolved in MeCN (1 mL) and to it was added a solution of 1-((3R,4R)-4-methylpiperidin-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine hydrochloride (0.06 g, 0.21 mmol, Example #5 Step J) and DIEA (0.04 mL, 0.21 mmol) in MeCN (1 mL). The reaction mixture was heated to about 70° C. for about 2 h. The solvent was removed under reduced pressure. The crude residue was dissolved in DCM (5 mL) and washed with water (2 mL), brine (3 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by RP-HPLC (Table 1, Method e) to give (3R,4R)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methyl-N-(pyrimidin-4-yl)piperidine-1-carboxamide (0.007 g, 9%): LC/MS (Table 1, Method b) Rt=1.40 min; MS m/z 377 (M+H)+.

Provenance & Evidence