Dimethylamine, hydrochloride → (-)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N,N-dimethylacetamide

Participants

Reaction Steps

A solution of 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetic acid (0.153 mmol) in dichloromethane (1 mL) was treated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.230 mmol) and 4-(dimethylamino)pyridine (0.766 mmol). This mixture was stirred at room temperature for 10 min at which point dimethylamine hydrochloride (0.306 mmol) was added. The reaction vessel was sealed and the reaction was stirred at room temperature overnight. At this point an additional portion of N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.230 mmol) was added. The reaction vessel was sealed and the reaction was stirred at room temperature overnight. The resulting reaction mixture was concentrated to dryness under a stream of nitrogen. Purification of the residue by reverse phase HPLC (20-65% acetonitrile/water with 0.1% NH4OH) followed by chiral HPLC (Chromegachiral CC4, methanol) and lyophilization from water (w/25% acetonitrile) afforded the title compound as a solid (25 mg, 30%). MS(ES)+ m/e 517.4 [M+H]+, >99% ee, αD=−69 deg (c=0.01, methanol).

Provenance & Evidence