Water → 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester

HRID 2279095노트

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HRID 2279095 반응식
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10](Br)[CH:11]=1)=[O:5])[CH3:2].[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10]([C:33]2[CH:34]=[CH:35][C:30]([O:29][CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28][O:23]3)=[CH:31][CH:32]=2)[CH:11]=1)=[O:5])[CH3:2]

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 50176524-(Tetrahydro-2H-pyran-2-yloxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 866803196-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester

생성물 1

HCID 900142043-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester수율 92.3%

시약·촉매·용매 1

HCID 18180031Water 1,2-dimethoxyethane용매

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온도
85 °C

실험 절차

To a mixture of 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (6.00 g), 4-(tetrahydro-2H-pyran-2-yloxy)-phenylboronic acid (4.34 g) and potassium carbonate (2.93 g) in DME/water (v/v=2/1, 200 mL) was added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.42 g) and the mixture was stirred at 85° C. for 90 min. To the mixture water was added and it was extracted with ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate) to give 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (7.00 g, 92%). This material was dissolved in isopropanol (30 mL), and 1N sodium hydroxide solution (15 mL) was added. The solution was stirred overnight, then the mixture was contentrated in vacuo to about a third of its volume. The precipitated solid was isolated by filtration and dried in air giving the sodium salt of 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (6.2 g, 87%).

후처리

  1. additionwas added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.42 g)
  2. extractionit was extracted with ethyl acetate
  3. washThe organic phase was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate)

출처 및 근거

ORD 기록
ord-a68ca50c3c04413caededd8412e0ebbd
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133181B2

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