反应详情

温度

50 °C

1N Aqueous solution of sodium hydroxide (2 ml) was added at room temperature to a solution of 2-[4-(trifluoromethyl)phenyl]thiazole-4-carboxylic acid ethyl ester (300 mg) described in Reference Example 178 in tetrahydrofuran (2 ml) and stirred at 50° C. for 4.5 hours. After the reaction, 1N aqueous solution of hydrochloric acid (2 ml) was added, the solvent was evaporated and the residue was azeotropically distilled twice with toluene. N,N-Dimethylformamide (catalytic amounts) and thionyl chloride (2 ml) were added to the resulting residue at room temperature, stirred at 80° C. for an hour, and an excess amount of thinly chloride was evaporated. The resulting reaction solution was dissolved in dichloromethane (5 ml), triethylamine (416 μl) and 5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridine-3-amine (327 mg) were added and stirred at room temperature for 20 minutes. After the reaction, water was added, extracted with chloroform and the solvent was evaporated. The resulting residue was purified with a basic silica gel column chromatography (n-hexane/ethyl acetate) to give the titled compound (321 mg) as a white solid.

1. additionwas added
2. customthe solvent was evaporated
3. distillationthe residue was azeotropically distilled twice with toluene
4. additionN,N-Dimethylformamide (catalytic amounts) and thionyl chloride (2 ml) were added to the resulting residue at room temperature
5. stirringstirred at 80° C. for an hour
6. customan excess amount of thinly chloride was evaporated
7. customThe resulting reaction solution
8. stirringstirred at room temperature for 20 minutes
9. additionwas added
10. extractionextracted with chloroform
11. customthe solvent was evaporated
12. customThe resulting residue was purified with a basic silica gel column chromatography (n-hexane/ethyl acetate)