تفاعل #71971

معادلة التفاعل

cis(±)-4-Chloro-N-{3-(2,2-difluoroethoxy)-1-(trifluoroacetyl)piperidin-4-yl}-5-ethyl-1H-imidazole-2-carboxamide

lithium hydroxide

Diisopropylethylamine

ethyl 2-bromo-1,3-thiazole-5-carboxylate

hydrochloric acid

→

title compound

المردود 74.0%

Ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-(2,2-difluoroethoxy)piperidin-1-yl)-1,3-thiazole-5-carboxylate

المردود 74.0%

المذيبات

methanol

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent was evaporated under reduced pressure
2. 2
   workup.DISSOLUTIONThe residue was dissolved in DMA (5 mL)
3. 3
   workup.STIRRINGthe mixture was stirred at 75° C. for one hour
4. 4
   غسيلDilution with ethyl acetate, washing with water and brine
5. 5
   تجفيفdrying over anhydrous magnesium sulfate, and concentration under reduced pressure
6. 6
   أخرىgave a residue, which
7. 7
   أخرىwas purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 2/3, 3/2, 4/1)

الإجراء التجريبي

cis(±)-4-Chloro-N-{3-(2,2-difluoroethoxy)-1-(trifluoroacetyl)piperidin-4-yl}-5-ethyl-1H-imidazole-2-carboxamide obtained in Example (121f) (144 mg, 0.33 mmol) was dissolved in methanol (4 mL). A 2 N aqueous lithium hydroxide solution (0.4 mL) was added, and the mixture was stirred at 40° C. for 40 minutes. The pH was adjusted to 4 by adding a 1 N aqueous hydrochloric acid solution, and the solvent was evaporated under reduced pressure. The residue was dissolved in DMA (5 mL). Diisopropylethylamine (130 mg, 1 mmol) and ethyl 2-bromo-1,3-thiazole-5-carboxylate (155 mg, 0.66 mmol) were added, and the mixture was stirred at 75° C. for one hour. Dilution with ethyl acetate, washing with water and brine, drying over anhydrous magnesium sulfate, and concentration under reduced pressure gave a residue, which was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 2/3, 3/2, 4/1) to obtain 0.12 g of the title compound as a colorless amorphous solid (74%).

المصدر