反应详情

Pyrrolidine-1-carboxylic acid [4-(4-amino-3-chlorophenoxy)pyridin-2-yl]amide (79.6 mg) was dissolved in N,N-dimethylformamide (1.5 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (142 mg), triethylamine (0.100 ml), and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (318 mg) were added thereto at 50° C., followed by stirring at the same temperature for 2 hrs and 30 min. The reaction mixture was cooled down to room temperature, and partitioned between ethyl acetate and a 1 N aqueous solution of sodium hydroxide. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; ethyl acetate). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (5 ml)-hexane (5 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (94.5 mg, 76.9%) as white powder.

1. customat 50° C.
2. custompartitioned between ethyl acetate
3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was evaporated
6. customto give a residue, which
7. customwas then purified by silica gel column chromatography (eluent; ethyl acetate)
8. additionFractions containing the target compound
9. concentrationwere concentrated
10. customto give a residue
11. filtrationThe solid was filtered off
12. customdried under aeration