反应详情

4-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (47.8 mg) was dissolved in N,N-dimethylformamide (2 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (89.3 mg), triethylamine (0.063 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (200 mg) were added thereto at 50° C., followed by stirring at the same temperature for 1 hr. The reaction mixture was cooled down to room temperature, followed by further stirring overnight. The reaction mixture was 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 (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:ethanol=95:5). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether-hexane (1:1) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (28.7 mg, 38.4%) as pale yellow powder.

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