Water → 4-[4-(4-Ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester

HRID 1931722노트

반응식

HRID 1931722 반응식
Cl[C:2]([O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:3].FC(F)(F)C(O)=O.[CH2:17]([O:19][C:20]1[CH:41]=[CH:40][C:23]([O:24][C:25]2[N:30]=[CH:29][N:28]=[C:27]3[N:31]([CH:34]4[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]4)[N:32]=[CH:33][C:26]=23)=[C:22]([F:42])[CH:21]=1)[CH3:18].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:5]1([O:4][C:2]([N:37]2[CH2:38][CH2:39][CH:34]([N:31]3[C:27]4=[N:28][CH:29]=[N:30][C:25]([O:24][C:23]5[CH:40]=[CH:41][C:20]([O:19][CH2:17][CH3:18])=[CH:21][C:22]=5[F:42])=[C:26]4[CH:33]=[N:32]3)[CH2:35][CH2:36]2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1

참가 물질

6

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2735892Cyclopentyl chloroformateHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2회

생성물 1

HCID 579649964-[4-(4-Ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester수율 99%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Cyclopentyl chloroformate (12 mg, 0.078 mmol) was added to a mixture of 4-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 29; 28 mg, 0.078 mmol), diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction was stirred at room temperature overnight. Water was added to quench the reaction and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried (sodium sulfate), filtered, evaporated and purified by flash chromatography on silica gel, eluting with 4% methanol/dichloromethane to give 4-[4-(4-ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (36 mg, 99%) as a white solid. Mass spectrum MH+=470.

후처리

  1. customto quench
  2. customthe reaction
  3. extractionthe aqueous layer was extracted three times with dichloromethane
  4. dry with materialThe combined organic layers were dried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by flash chromatography on silica gel
  8. washeluting with 4% methanol/dichloromethane

출처 및 근거

ORD 기록
ord-5cc5e7673e4e4a61b387c52055167a29
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

반응 노트

불러오는 중…