반응 #616948

반응 방정식

pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(5-chloro-2-difluoromethoxyphenyl)-1-piperidin-4-yl-1H-pyrazol-4-yl]amide

(3-bromo-propyl)-carbamic acid tert-butyl ester

potassium carbonate

→

[3-(4-{3-(5-chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidin-1-yl)propyl]carbamic acid tert-butyl ester

수율 101.5%

용매

DMF

water

반응 조건

후처리

1. 1
   온도to cool to ambient temperature
2. 2
   추출extracted with dichloromethane
3. 3
   기타The organic layer was separated
4. 4
   세척washed with brine
5. 5
   건조dried (Na2SO4)
6. 6
   기타evaporated
7. 7
   기타The resultant residue was chromatographed on silica eluting with dichloromethane on a gradient of 2M ammonia in methanol (0-6%)

실험 절차

A mixture of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(5-chloro-2-difluoromethoxyphenyl)-1-piperidin-4-yl-1H-pyrazol-4-yl]amide (100 mg, 0.20 mmol), (3-bromo-propyl)-carbamic acid tert-butyl ester (71 mg, 0.3 mmol) and potassium carbonate (45 mg, 0.32 mmol) in DMF (2 mL) was heated at 60° C. for 1.5 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with water and extracted with dichloromethane. The organic layer was separated, washed with brine, dried (Na2SO4) and evaporated. The resultant residue was chromatographed on silica eluting with dichloromethane on a gradient of 2M ammonia in methanol (0-6%) to give [3-(4-{3-(5-chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidin-1-yl)propyl]carbamic acid tert-butyl ester as a yellow oil (131 mg, 100%). LCMS (Method 4) [M+H]+=675.0, RT=2.86 min.

출처