反应详情

温度

80 °C

Thionyl chloride (6.6 ml) and N,N-dimethylformamide (catalytic amounts) were added at room temperature to a solution of 5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylic acid (8.17 g) described in Reference Example 8 in toluene (150 ml) and stirred at 80° C. for an hour. The solvent and an excess amount of thionyl chloride were evaporated. Pyridine (200 ml) was added to the resulting reaction mixture, and a pyridine (250 ml) solution of (S)-5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridine-3-amine (7.5 g), which was derived from the second peak fractions when 5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridine-3-amine of Reference Example 108 was optically fractionated with a chiral column, was added and stirred at 50° C. for two hours. After the reaction, the reaction solution was left stand, triethylamine (40 ml) and water were added and the precipitate was filtered. The resulting solid was dissolved in acetic acid (7.5 ml), water (7.5 ml) and ethanol (750 ml), activated charcoal was added and stirred at 40° C. for an hour. The mixture was filtered through Celite, pH was adjusted to 8 by the addition of 1N aqueous solution of sodium hydroxide and the precipitate was collected by filtration. The resulting solid was washed with water and dried at 60° C. under current of air to give the titled compound (11.3 g) as a white solid.

1. customThe solvent and an excess amount of thionyl chloride were evaporated
2. additionPyridine (200 ml) was added to the resulting reaction mixture
3. additionwas added
4. stirringstirred at 50° C. for two hours
5. customAfter the reaction
6. additionwere added
7. filtrationthe precipitate was filtered
8. dissolutionThe resulting solid was dissolved in acetic acid (7.5 ml)
9. additionwater (7.5 ml) and ethanol (750 ml), activated charcoal was added
10. stirringstirred at 40° C. for an hour
11. filtrationThe mixture was filtered through Celite, pH
12. additionwas adjusted to 8 by the addition of 1N aqueous solution of sodium hydroxide
13. filtrationthe precipitate was collected by filtration
14. washThe resulting solid was washed with water
15. customdried at 60° C. under current of air