反应详情

4-(Dimethylaminomethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (88 mg) was dissolved in N,N-dimethylformamide (2.5 ml). 1-(4-Fluorophenylcarbamoyl)cyclopropanecarboxylic acid (101 mg), triethylamine (0.0633 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (201 mg) were added under a nitrogen atmosphere at room temperature, followed by stirring overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with a 1N aqueous solution of sodium hydroxide and brine, 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 heptane to the resultant residue. The solid was collected by filtration, and dried under aeration to provide the titled compound as white powder (39.8 mg, 30%).

1. customLiquid-liquid separation
2. additionafter addition of ethyl acetate and water to the reaction mixture
3. washThe organic layer was washed with a 1N aqueous solution of sodium hydroxide and brine
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was removed
6. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
7. additionFractions containing the target compound
8. concentrationwere concentrated under reduced pressure
9. customA solid was precipitated by addition of heptane to the resultant residue
10. filtrationThe solid was collected by filtration
11. customdried under aeration