反应详情

温度

230 °C

A mixture of 3,5-dichloro-6-ethylpyrazine-2-carboxamide (200 mg), 3-chloro-4-methylsulfonylaniline (374 mg) and NMP (1 mL) was stirred at 230° C. for 1 hour using a microwave reaction system. Thereafter, trans-4-aminocyclohexanol (524 mg) was added to the reaction liquid and stirred at 190° C. for 30 minutes using a microwave reaction system. After cooling, the reaction liquid was partitioned using ethyl acetate and water, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=10:0 to 30:1) to give a crude product. This product was heated with ethanol and washed to give a light yellow solid. To the light yellow solid, ethyl acetate was added and heated, and insoluble materials were separated by filtration and the filtrate was concentrated. After the filtrate was concentrated, the residue was heated and washed with ethanol to give 3-{[3-chloro-4-(methylsulfonyl)phenyl]amino}-6-ethyl-5-[(trans-4-hydroxycyclohexyl)amino]pyrazine-2-carboxamide (39 mg) as a light yellow solid.

1. customa microwave reaction system
2. stirringstirred at 190° C. for 30 minutes
3. customa microwave reaction system
4. temperatureAfter cooling
5. customthe reaction liquid
6. customwas partitioned
7. washthe organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
8. dry with materialAfter drying over anhydrous magnesium sulfate
9. distillationthe solvent was distilled off
10. customthe residue was purified by silica gel column chromatography (eluent; chloroform:methanol=10:0 to 30:1)
11. customto give a crude product
12. washwashed
13. customto give a light yellow solid
14. temperatureheated
15. custominsoluble materials were separated by filtration
16. concentrationthe filtrate was concentrated
17. concentrationAfter the filtrate was concentrated
18. temperaturethe residue was heated
19. washwashed with ethanol