反应详情

2-(4-Fluorophenyl)acetyl chloride (135 mg) was dissolved in acetonitrile (5 ml) under a nitrogen atmosphere, and then potassium thiocyanate (152 mg) was added thereto at 60° C., followed by stirring at the same temperature for 1.5 hrs. The reaction mixture was cooled down to room temperature, and then a solution of 4-(4-amino-2-fluorophenoxy)-6-[(pyrrolidin-1-yl) carbonylamino]pyrimidine (99.6 mg) in acetonitrile (3 ml) was added thereto, followed by stirring for 15 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. 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 under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, which was suspended in diethyl ether (5 ml)-hexane (5 ml). The solid was filtered off and dried under aeration to provide the titled compound (111.8 mg, 69.5%) as a pale yellow solid.

1. customat 60° C.
2. stirringby stirring for 15 min
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 under a reduced pressure
7. customto give a residue, which
8. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3)
9. additionFractions containing the target compound
10. concentrationwere concentrated
11. customto give a residue, which
12. filtrationThe solid was filtered off
13. customdried under aeration