Acetone → HCID 16048989, compound

Participants

Reaction Steps

A solution of 1-[5-(5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)-2-pyridinyl]-2-pyrrolidinone (may be prepared as described in Description 19) (37 mg, 0.12 mmol) in dichloromethane (2.5 ml) was treated with acetone (0.018 ml, 0.25 mmol) and then stirred under Argon for 20 min and then treated with sodium triacetoxyborohydride (53 mg, 0.25 mmol) and the resulting mixture stirred under Argon at room temperature for 16.5 hours. 2 hours later, more acetone (2 eq) was then added, followed 5 min later by more sodium triacetoxyborohydride (2 eq) and the mixture stirred under Argon at room temperature for 5 hours. The mixture was then diluted with methanol and then purified by SCX eluting with methanol and then 2M ammonia in methanol to give a 73:27 (by LCMS DAD) 88:12 (by LCMS ELSD) mixture of 1-{5-[6-(1-methylethyl)-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl]-2-pyridinyl}-2-pyrrolidinone hydrochloride (E43) and 1-[5-(5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)-2-pyridinyl]-2-pyrrolidinone (D19) (33 mg). A solution of this mixture in dichloromethane (2.5 ml) was treated with acetone (0.018 ml, 0.25 mmol) under Argon and the mixture stirred for 2-3 min at room temperature. Sodium triacetoxyborohydride (53 mg, 0.25 mmol) was then added and the mixture stirred under Argon at room temperature for 15.75 hours. After an additional 1 hour, more acetone (5 eq) was added followed 5 min later by more sodium triacetoxyborohydride and the mixture stirred at room temperature under Argon for an additional 7.75 h. The mixture was then diluted with methanol and purified by SCX eluting with methanol then methanol/NH3 (2M). Purified further by SPE (Si) eluting with dichloromethane:methanol 50:1→25:1→10:1→5:1→2:1. Purified further by Mass Directed Autopreparation followed by SCX eluting with methanol then methanol/NH3 (2M) to afford the title product (E43).

Provenance & Evidence