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

HRID 1931627노트

반응식

HRID 1931627 반응식
Cl[C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3].FC(F)(F)C(O)=O.[CH2:15]([O:17][C:18]1[CH:39]=[CH:38][C:21]([O:22][C:23]2[N:28]=[CH:27][N:26]=[C:25]3[N:29]([CH:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)[N:30]=[CH:31][C:24]=23)=[C:20]([F:40])[CH:19]=1)[CH3:16].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:5]([O:4][C:2]([N:35]1[CH2:36][CH2:37][CH:32]([N:29]2[C:25]3=[N:26][CH:27]=[N:28][C:23]([O:22][C:21]4[CH:38]=[CH:39][C:18]([O:17][CH2:15][CH3:16])=[CH:19][C:20]=4[F:40])=[C:24]3[CH:31]=[N:30]2)[CH2:33][CH2:34]1)=[O:3])([CH3:7])[CH3:6]

참가 물질

6

반응물 4

HCID 962WaterHCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2회

생성물 1

HCID 445141074-[4-(4-Ethoxy-2-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester수율 80%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Isopropyl chloroformate (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 1 M in toluene; 0.079 ml, 0.079 mol) 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), and diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction mixture 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-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (27 mg, 80%) as a white solid. Mass spectrum MH+=444.

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-ccc304c697684e2285c124d684373d75
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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