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 2279120ノート

反応式

HRID 2279120 の反応式
[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]

参加物

7

反応物 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

生成物 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 ester収率 27%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-dfada8d87f204f3b89a077c4e44a22a6
出典データセット
uspto-grants-2015_09
特許番号
US09133181B2

反応ノート

読み込み中…