Triethylamine → N-[4-({2-[({4-[(Dimethylamino)methyl]piperidin-1-yl]carbonyl)amino]pyridin-4-yl}oxy)-3-fluorophenyl]-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide

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Reaction Steps

4-(Dimethylaminomethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (114 mg) was dissolved in N,N-dimethylformamide (4.0 ml). 1-(4-Fluorophenylcarbamoyl)cyclobutanecarboxylic acid (279 mg), triethylamine (0.164 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (520 mg) were added under a nitrogen atmosphere at room temperature and stirred overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with 0.5N hydrochloric acid (4 times), water, a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was removed and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the target compound were concentrated under reduced pressure. A solid was precipitated by addition of a mixture of diethyl ether and heptane (1:3) to the resultant residue. The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (19.1 mg, 11%).

Provenance & Evidence