反应详情

2-Phenylacetyl chloride (100 mg) was dissolved in acetonitrile (2 ml) under a nitrogen atmosphere, and then potassium thiocyanate (126 mg) was added thereto at 50° C., followed by stirring at the same temperature for 1.5 hrs. A solution of 4-(4-amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (41 mg) in acetonitrile (4 ml) was added thereto, followed by stirring at room temperature for 2.5 hr. The reaction mixture was cooled down to room temperature, and then partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine, 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=1:4). Fractions containing the target compound were concentrated to give a residue, to which a small amount of diethyl ether was added to precipitate crystals. A suspension containing the crystals was diluted with a small amount of hexane. The crystals were filtered off and dried under aeration to provide the titled compound (21.4 mg, 34%) as pale yellow crystals.

1. customat 50° C.
2. stirringby stirring at room temperature for 2.5 hr
3. custompartitioned between ethyl acetate
4. washThe organic layer was washed with brine
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=1:4)
9. additionFractions containing the target compound
10. concentrationwere concentrated
11. customto give a residue
12. customto precipitate crystals
13. additionA suspension containing the crystals
14. additionwas diluted with a small amount of hexane
15. filtrationThe crystals were filtered off
16. customdried under aeration