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Acetonitrile → tert-Butyl 4-(6-(5-(cyanomethyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 1775049
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HRID 1775049 반응식
C([Li])CCC.[C:6](#[N:8])[CH3:7].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[C:36]4[C:31](=[CH:32][N:33]=[C:34](Br)[CH:35]=4)[N:30]([CH:38]4[CH2:43][CH2:42][CH2:41][CH2:40][O:39]4)[N:29]=3)[N:23]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[NH4+].[Cl-]>CCCCCC.O1CCCC1>[C:6]([CH2:7][C:34]1[CH:35]=[C:36]2[C:28]([C:24]3[N:23]=[C:22]([N:19]4[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:15])[CH2:17][CH2:18]4)[CH:27]=[CH:26][CH:25]=3)=[N:29][N:30]([CH:38]3[CH2:43][CH2:42][CH2:41][CH2:40][O:39]3)[C:31]2=[CH:32][N:33]=1)#[N:8]
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참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 25517Ammonium ChlorideHCID 866766914-{6-[5-bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

생성물 1

HCID 71261625tert-Butyl 4-(6-(5-(cyanomethyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxylate
수율 17.5%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8058Hexane용매

실험 절차

A solution of 0.940 mL of 1.6 M of n-Butyllithium in hexane was added dropwise to a solution of 0.102 mL, (1.95 mmol) of acetonitrile in tetrahydrofuran at −78° C. The mixture was stirred for 30 min and a solution of 272 mg (0.500 mmol) of 4-{6-[5-bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester was added. The brown mixture was stirred for 30 min at −50° C. and 2 ml of saturated aqueous NH4Cl was added. The mixture was allowed to warm to room temperature and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over MgSO4 and concentrated. The residue was purified via silica gel chromatography using a gradient of ethyl acetate in heptane to afford 44 mg (17%) of tert-Butyl 4-(6-(5-(cyanomethyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxylate. ESI MS m/z 504.2 (M+1).

후처리

  1. stirringThe brown mixture was stirred for 30 min at −50° C.
  2. extractionextracted with ethyl acetate
  3. washThe organic extracts were washed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified via silica gel chromatography

출처 및 근거

ORD 기록
ord-f89f4c16c6e542ea8e1e6a2093ea6be7
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09260425B2

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