反应详情

N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide (15 mg, 0.049 mmol) synthesized in Example 215 was suspended in tetrahydrofuran (0.5 ml) at room temperature; triethylamine (17 μl, 0.122 mmol) and phenyl chloroformate (14 μl, 0.072 mmol) was added thereto while stirring; and the reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, this was subjected to extraction with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. N,N-Dimethylformamide (0.5 ml) and 4-(1-pyrrolidinyl)piperidine (28 mg, 0.18 mmol) was added to a portion of the residue (14 mg); and the reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was dried over anhydrous sodium sulfate. This was concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol). The resultant was washed with a solvent mixture (ether: hexane=1:1); and the solid was filtered off to yield the title compound as crystals (6 mg).

1. stirringand the reaction mixture was stirred at room temperature for 2 hours
2. extractionthis was subjected to extraction with ethyl acetate
3. washwashed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. stirringand the reaction mixture was stirred at room temperature overnight
7. customThe reaction mixture was partitioned between ethyl acetate and water
8. dry with materialand the organic layer was dried over anhydrous sodium sulfate
9. concentrationThis was concentrated under reduced pressure
10. customand the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol)
11. washThe resultant was washed with a solvent mixture (ether: hexane=1:1)
12. filtrationand the solid was filtered off