Ammonium Bromide → 2-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetamide

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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 (0.257 mmol) in dichloromethane (2 mL) was treated with N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.386 mmol) and 4-(dimethylamino)pyridine (1.030 mmol) at room temperature. This mixture was stirred for ten minutes at which point ammonium bromide (0.309 mmol) was added. The reaction was allowed to stir at room temperature overnight. The reaction was then concentrated to dryness under a stream of nitrogen. The resulting crude product was purified by reverse phase HPLC (10-40% acetonitrile with 0.1% TFA/water with 0.1% TFA). Fractions containing the desired product were combined and the pH of the resulting mixture was adjusted to ˜10 with 30% w/v aq ammonium hydroxide. This mixture was concentrated to a minimal volume in vacuo and was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Lyophilization from water afforded the title product as a white solid (47 mg, 35%). MS(ES)+ m/e 489.5 [M+H]+.

Provenance & Evidence