反应详情

An acetonitrile (5 ml) solution of the [5-chloro-4-[(4-chlorophenylsulfonyl)(2,5-difluorophenyl)methyl]pyridin-2-yl]amine (101 mg, 0.235 mmol) obtained in Example 196, 4-methylpiperazine-1-sulfonyl chloride hydrochloride (126 mg, 0.534 mmol) and triethylamine (150 μl, 1.07 mmol) was heated under reflux for 23 hours. To the reaction mixture were added 4-methylpiperazine-1-sulfonyl chloride hydrochloride (126 mg, 0.534 mmol) and triethylamine (150 μl, 1.07 mmol). The resulting mixture was heated under reflux for 22 hours. The reaction mixture was returned to room temperature and then, concentrated under reduced pressure. To the residue thus obtained was added water and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the methanol:methylene chloride (=1:20) eluate was concentrated under reduced pressure to give the title compound (34 mg, 0.057 mmol, 16%) as a pale yellow solid.

1. temperatureunder reflux for 23 hours
2. temperatureThe resulting mixture was heated
3. temperatureunder reflux for 22 hours
4. customwas returned to room temperature
5. concentrationconcentrated under reduced pressure
6. customTo the residue thus obtained
7. extractionthe resulting mixture was extracted with ethyl acetate
8. washThe organic layer was washed with brine
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationThe filtrate was concentrated under reduced pressure
12. customThe residue thus obtained
13. concentrationmethylene chloride (=1:20) eluate was concentrated under reduced pressure