Diisopropylethylamine → 4-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester

HRID 1931723노트

반응식

HRID 1931723 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.[NH:17]1[CH2:22][CH2:21][CH:20]([N:23]2[C:27]3=[N:28][CH:29]=[N:30][C:31]([O:32][C:33]4[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=4[C:35]#[N:36])=[C:26]3[CH:25]=[N:24]2)[CH2:19][CH2:18]1.C(OC(N1CCC(N2C3=NC=NC(OC4C=CC=CC=4C#N)=C3C=N2)CC1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(OC1C=CC(OC2N=CN=C3N(C4CCNCC4)N=CC=23)=C(F)C=1)C.C(N(C(C)C)CC)(C)C>ClCCl.O>[CH:5]1([O:4][C:2]([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[C:27]4=[N:28][CH:29]=[N:30][C:31]([O:32][C:33]5[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=5[C:35]#[N:36])=[C:26]4[CH:25]=[N:24]3)[CH2:19][CH2:18]2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 2735892Cyclopentyl chloroformateHCID 445144014-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate saltHCID 669154562-(1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-yloxy)-benzonitrile trifluoroacetate salt

생성물 1

HCID 579649284-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester수율 72%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

Cyclopentyl chloroformate (51 mg, 0.344 mmol) was added to a mixture of 2-(1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-yloxy)-benzonitrile trifluoroacetate salt (which was prepared from 4-[4-(2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester [Example 45] following the procedure described for the preparation of Intermediate 29; 150 mg, 0.344 mmol), diisopropylethylamine (133 mg, 1.03 mmol) in dichloromethane (6 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-(2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (107 mg, 72%) as a white solid. Mass spectrum MH+=433.

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-35bf9104722d4da7b711e280f6a232c8
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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