5-(Trifluoromethyl)-1H-indazole → HCID 71279862、化合物

HRID 246498ノート

反応式

HRID 246498 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:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][N:32]=[CH:31]2.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:33]3[C:34]4[C:30](=[CH:29][C:28]([C:27]([F:26])([F:38])[F:37])=[CH:36][CH:35]=4)[CH:31]=[N:32]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 214092225-(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 71279862HCID 71279862、化合物収率 44.1%

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 (200 mg, 468 μmol), 5-(trifluoromethyl)-1H-indazole (87.1 mg, 468 μmol) in dioxane (3.5 mL) was added sodium tert-butoxide (98.9 mg, 1.03 mmol) and bis(tri-tert-butylphosphine)palladium(0) (23.9 mg, 46.8 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, 0-30% ethyl acetate in hexanes) gave N-tert-butyl-2-(5-(trifluoromethyl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (110 mg, 44%). 1H NMR (CDCl3) δ: 9.20 (s, 1H), 8.69-8.74 (m, 2H), 8.42 (s, 2H), 8.39 (d, J=0.8 Hz, 1H), 8.33-8.36 (m, 1H), 8.18 (s, 2H), 7.70-7.74 (m, 1H), 5.73 (s, 2H), 3.59 (dd, J=8.9, 7.7 Hz, 2H), 1.63 (s, 9H), 0.92-0.98 (m, 2H), −0.04 (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, 0-30% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-b20a27233ade40188a3a0bd1fe23eff8
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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