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 246486Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246486
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]

Komponenten

6

Edukt 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

Produkt 1

HCID 71279727N-tert-Butyl-2-(6-(trifluoromethyl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 49,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-f171075e024a4696a4d2fd40745691db
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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