5-(Trifluoromethyl)-1H-indazole → HCID 71279862, 화합물

HRID 246498노트

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HRID 246498 반응식
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]

참가 물질

6

반응물 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

생성물 1

HCID 71279862HCID 71279862, 화합물수율 44.1%

시약·촉매·용매 2

HCID 178418851HCID 178418851, 화합물촉매HCID 312751,4-Dioxane용매

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온도
125 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b20a27233ade40188a3a0bd1fe23eff8
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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