Diisopropylethylamine → N-[4-bromo-3-(methyloxy)phenyl]-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask was added triphosgene (0.514 g, 1.732 mmol) and dichloromethane (30 mL) under nitrogen, and the solution was cooled to −78° C. In a separate vial, 3-methoxy 4-bromoaniline (1 g, 4.95 mmol) was dissolved in dichloromethane (20 mL) and Hunig's base (1.753 mL, 9.90 mmol) was added. This solution was slowly added to the cooled solution and then the reaction was allowed to warm to room temperature. Analysis by LCMS indicated desired intermediate formation. The reaction was cooled again to −78° C. and 2-[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetohydrazide (0.575 g, 2.72 mmol) in dichloromethane (5 mL) was added slowly. The reaction was allowed to warm to room temperature and analysis by LCMS indicated desired product formation. The reaction was poured into a reparatory funnel and partitioned with saturated aq sodium bicarbonate. The aqueous layer was extracted with dichloromethane (3×) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to an oil. The residue was purified by silica gel chromatography (0-40% isopropanol/ethyl acetate). The desired product fractions were combined and concentrated in vacuo to afford the title product as a tan solid (500 mg, 42%). MS(ES)+ m/e 439.0, 441.1 M+H]+.

Provenance & Evidence