1-Pyrrolidineethanamine → 2-(2-chloro-4-(morpholinomethyl)phenyl)-6-fluoro-N-(2-(pyrrolidin-1-yl)ethyl)quinoline-4-carboxamide

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Reaction Steps

A mixture of 2-(2-chloro-4-(morpholinomethyl)phenyl)-6-fluoroquinoline-4-carboxylic acid (303 mg, 0.76 mmol) (preparation 18) in DCM (6 ml) was prepared at room temperature and N-methylmorpholine (0.166 ml, 1.51 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (159 mg, 0.91 mmol) added and the mixture stirred for 1 h in a sealed vial. 2-(Pyrrolidin-1-yl)ethanamine (0.143 ml, 1.13 mmol) was then added and the mixture stirred in a sealed vial for 17 h. The mixture was then diluted with DCM (5 ml) and the organic layers washed with water (2×3 ml) and filtered through a phase separator and the organic layers concentrated under reduced pressure and purified by column chromatography (0-10% 7M NH3 in MeOH/DCM) to afford an off white solid. Analysis by 1HNMR showed impurities and the mixture was further purified by mass directed autopreparative HPLC to afford the desired product as an off-white solid (228 mg, 0.46 mmol, 61%).

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