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Water → 2,2-Diethyl-4-[6-(3-fluoro-4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 2279123
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HRID 2279123 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[N:11]([CH2:16][C:17]2[CH:22]=[C:21](Br)[N:20]=[C:19]3[N:24]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][O:29]4)[N:25]=[C:26]([CH3:27])[C:18]=23)[CH2:10][C:9]1([CH2:36][CH3:37])[CH2:34][CH3:35])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][C:44]=1[OH:45].O.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[N:11]([CH2:16][C:17]2[CH:22]=[C:21]([C:41]3[CH:42]=[CH:43][C:44]([OH:45])=[C:39]([F:38])[CH:40]=3)[N:20]=[C:19]3[N:24]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][O:29]4)[N:25]=[C:26]([CH3:27])[C:18]=23)[CH2:10][C:9]1([CH2:36][CH3:37])[CH2:34][CH3:35])=[O:7])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

7

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HCID 962WaterHCID 11430Potassium CarbonateHCID 230053613-Fluoro-4-hydroxybenzeneboronic acidHCID 900140904-[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,2-diethyl-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 136623246
2,2-Diethyl-4-[6-(3-fluoro-4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester
수율 34%

시약·촉매·용매 2

HCID 178418851HCID 178418851, 화합물촉매HCID 8857Ethyl Acetate용매

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온도
120 °C

실험 절차

To a solution of 150 mg 4-[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,2-diethyl-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester and 48 mg 3-fluoro-4-hydroxy-phenylboronic acid in 8 ml of DEM and 0.45 ml of water were added 40 mg of potassium carbonate. To the degassed reaction mixture 4 mg of bis(tri-tert-butyl-phosphin)palladium(0) were added. The reaction was heated to 120° C. in a microwave reactor for 2 h. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate twice. The combined organic layers were dried and concentrated in vacuo. The resulting residue was purified by HPLC. 53 mg (34%) of the title compound were obtained.

후처리

  1. additionwere added
  2. washwashed with water
  3. extractionThe aqueous phase was extracted with ethyl acetate twice
  4. customThe combined organic layers were dried
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by HPLC

출처 및 근거

ORD 기록
ord-0693a5f240374358bac95c4aa82bff6c
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09133181B2

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