3-methoxy-1H-indazole → N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246515ノート

反応式

HRID 246515 の反応式
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])=[O:12])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.[CH3:27][O:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][N:30]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.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>[OH:16][CH2:15][C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:31]3[C:32]4[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:29]([O:28][CH3:27])=[N:30]3)[N:3]=2)[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1)=[O:12])([CH3:18])[CH3:17]

参加物

6

反応物 3

HCID 5195813-methoxy-1H-indazoleHCID 23676156Sodium t-butoxideHCID 715756472-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

生成物 1

HCID 71279674N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 80%

試薬・触媒・溶媒 2

HCID 178418851HCID 178418851、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
125 °C

実験手順

To a stirred solution of 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 338 μmol), 3-methoxy-1H-indazole (50.1 mg, 338 μmol) in dioxane (2 mL) was added sodium tert-butoxide (71.5 mg, 744 μmol) and bis(tri-tert-butylphosphine)palladium(0) (17.3 mg, 33.8 μmol). The mixture was degassed then heated in sealed tube at 125° C. for 15 h. The mixture was cooled, filtered through celite, and the filter cake washed with ethyl acetate. The combined filtrates were concentrated in vacuo and the crude residue purified by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) to give N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (138 mg, 80%).

後処理

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled
  3. filtrationfiltered through celite
  4. washthe filter cake washed with ethyl acetate
  5. concentrationThe combined filtrates were concentrated in vacuo
  6. customthe crude residue purified by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-f5fc8457b4674374975a79ecd3f8ae1d
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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