Water → (S)-5-Methyl-N-{5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

関与物質

反応条件

反応手順

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.

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