Diisopropylethylamine → 4-[4-(6-Cyano-2,3-difluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester

HRID 1931724노트

반응식

HRID 1931724 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.[F:17][C:18]1[C:19]([O:27][C:28]2[N:33]=[CH:32][N:31]=[C:30]3[N:34]([CH:37]4[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]4)[N:35]=[CH:36][C:29]=23)=[C:20]([CH:23]=[CH:24][C:25]=1[F:26])[C:21]#[N:22].C(OC(N1CCC(N2C3=NC=NC(OC4C(C#N)=CC=C(F)C=4F)=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:40]2[CH2:39][CH2:38][CH:37]([N:34]3[C:30]4=[N:31][CH:32]=[N:33][C:28]([O:27][C:19]5[C:20]([C:21]#[N:22])=[CH:23][CH:24]=[C:25]([F:26])[C:18]=5[F:17])=[C:29]4[CH:36]=[N:35]3)[CH2:42][CH2:41]2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 2735892Cyclopentyl chloroformateHCID 579649274-[4-(6-Cyano-2,3-difluoro-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 690162343,4-difluoro-2-(1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-yloxy)-benzonitrile trifluoroacetate salt

생성물 1

HCID 579650264-[4-(6-Cyano-2,3-difluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester수율 90%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

Cyclopentyl chloroformate (3B Scientific Corporation, Libertyville, Ill., USA; 46 mg, 0.31 mmol) was added to a mixture of 3,4-difluoro-2-(1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-yloxy)-benzonitrile trifluoroacetate salt (which was prepared from 4-[4-(6-cyano-2,3-difluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester [Example 49] following the procedure described for the preparation of Intermediate 29; 145 mg, 0.31 mmol), diisopropylethylamine (120 mg, 0.93 mmol) in dichloromethane (10 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-(6-cyano-2,3-difluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (130 mg, 90%) as a white solid. Mass spectrum MH+=469.

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-2d14622cf0bd4b869419b94860cc3554
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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