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

HRID 2360697ノート

反応式

HRID 2360697 の反応式
[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].[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[C:33]([F:40])[CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=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:34]2[CH:35]=[CH:36][C:31]([O:30][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[CH:32][C:33]=2[F:40])[CH:11]=1)=[O:5])[CH3:2]

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27377864-Benzyloxy-2-fluorophenylboronic acidHCID 866803196-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester

生成物 1

HCID 866803186-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester収率 82.4%

試薬・触媒・溶媒 1

HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

To mixture of 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (21.0 g), 4-benzyloxy-2-fluorophenylboronic acid (16.8 g) and potassium carbonate (8.7 g) in DME/water (v/v=2/1, 300 mL) was added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.99 g) and the mixture was stirred at 85° C. for 90 min. To the mixture water was added and extracted with ethyl acetate. The organic phase was washed several times with water, finally with brine. Methanol was added and the precipitate formed was filtered off, dried in air to give 6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (23.0 g, 82% yield). This material was dissolved in isopropanol (100 mL), and 1N sodium hydroxide solution (140 mL) was added. The solution was stirred overnight, filtered, then the filtrate was adjusted to pH2-3 and the precipitate formed was dried in air giving 6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (18 g, 83%).

後処理

  1. additionwas added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.99 g)
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed several times with water
  4. additionMethanol was added
  5. customthe precipitate formed
  6. filtrationwas filtered off
  7. customdried in air

出典と根拠

ORDレコード
ord-b7567c81f9a54f0f9bf5238532422f22
出典データセット
uspto-grants-2014_04
特許番号
US08686150B2

反応ノート

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