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

HRID 2279120노트

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HRID 2279120 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([CH2:35][CH3:36])[CH3:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O.C(OCC)(=O)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:38]([OH:37])=[CH:39][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([CH2:35][CH3:36])[CH3:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 900134844-[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2-ethyl-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 1366232192-Ethyl-4-[6-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl ester수율 27%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 18180031Water 1,2-dimethoxyethane용매

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온도
85 °C

실험 절차

To a degassed mixture of 70 mg 4-[6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2-ethyl-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl ester, 21 mg 4-hydroxyphenylboronic acid and 19 mg potassium carbonate in DME/water (v/v=2/1, 0.7 mL) at r.t. and under Ar-atmosphere 2 mg palladium(0) bis(tri-tert-butylphosphine) was added and the mixture was stirred at 85° C. for 75 min in a microwave reactor. To the mixture water and ethyl acetate were added, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were concentrated in vacuo and the resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate). 19 mg (27%) of the title compound were obtained.

후처리

  1. additionunder Ar-atmosphere 2 mg palladium(0) bis(tri-tert-butylphosphine) was added
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. concentrationThe combined organic phases were concentrated in vacuo
  5. customthe resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate)

출처 및 근거

ORD 기록
ord-dfada8d87f204f3b89a077c4e44a22a6
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133181B2

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