6-(trifluoromethyl)-1H-indazole → N-tert-Butyl-2-(6-(trifluoromethyl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246486ノート

反応式

HRID 246486 の反応式
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[F:26][C:27]([F:38])([F:37])[C:28]1[CH:36]=[C:35]2[C:31]([CH:32]=[N:33][NH:34]2)=[CH:30][CH:29]=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>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:34]3[C:35]4[C:31](=[CH:30][CH:29]=[C:28]([C:27]([F:26])([F:38])[F:37])[CH:36]=4)[CH:32]=[N:33]3)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

参加物

6

反応物 3

HCID 214555996-(trifluoromethyl)-1H-indazoleHCID 23676156Sodium t-butoxideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

生成物 1

HCID 71279727N-tert-Butyl-2-(6-(trifluoromethyl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 49.1%

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-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (180 mg, 421 μmol) and 6-(trifluoromethyl)-1H-indazole (78.4 mg, 421 μmol) in dioxane (2 mL) was added sodium tert-butoxide (89.0 mg, 927 μmol) and bis(tri-tert-butylphosphine)palladium(0) (21.5 mg, 42.1 μmol). The mixture was degassed then heated in sealed tube at 125° C. for two days. The mixture was cooled, filtered through celite, the cake washed with ethyl acetate, and the combined filtrates were concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave N-tert-Butyl-2-(6-(trifluoromethyl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (110 mg, 49%). 1H NMR (CDCl3) δ: 9.05 (s, 1H), 8.74 (d, J=0.5 Hz, 1H), 8.42 (s, 1H), 8.38 (d, J=1.0 Hz, 1H), 7.99 (d, J=8.5 Hz, 1H), 7.86 (s, 1H), 7.70 (s, 1H), 5.74 (s, 2H), 3.57-3.62 (m, 2H), 1.53 (s, 9H), 0.93-0.98 (m, 2H), −0.03 (s, 9H).

後処理

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

出典と根拠

ORDレコード
ord-f171075e024a4696a4d2fd40745691db
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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