Iodoethane → 2-(6-chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246445Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246445
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[CH:18][N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH2:36](I)[CH3:37]>CN(C=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[CH:18][N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH2:36][CH3:37])=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 712803652-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Produkt 1

HCID 712804172-(6-chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 61,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2-(6-Chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (120 mg, 247 μmol) was dissolved in DMF (1 mL) and cooled to 0° C. Sodium hydride (12.9 mg, 322 μmol) was added and the mixture was allowed to stir for 30 min at 0° C. Ethyl iodide (57.9 mg, 30.0 μL, 371 μmol) was added and the mixture was warmed to 20° C. After 15 h the mixture was diluted with water and extracted with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography (silica, 40 g Analogix pre-packed column, 20-50% ethyl acetate in hexanes, 15 minute gradient) to give 2-(6-chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (78 mg, 152 μmol, 61%) as a yellow powder. MS (M+Na)+=535; 1H NMR (CDCl3) δ: 9.26 (s, 1H), 8.44-8.49 (m, 1H), 8.39-8.42 (m, 1H), 8.20-8.28 (m, 1H), 7.47-7.56 (m, 1H), 7.23 (d, J=1.5 Hz, 1H), 5.67-5.77 (m, 2H), 4.43-4.59 (m, 1H), 4.13 (q, J=7.2 Hz, 1H), 3.52-3.67 (m, 1H), 1.57-1.65 (m, 4H), 1.42 (d, J=6.4 Hz, 4H), 0.88-1.01 (m, 2H)

Aufarbeitung

  1. temperaturethe mixture was warmed to 20° C
  2. extractionextracted with ethyl acetate
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography (silica, 40 g Analogix pre-packed column, 20-50% ethyl acetate in hexanes, 15 minute gradient)

Quellen und Nachweise

ORD-Eintrag
ord-b47bdd7d0ad54e43bdb5c071f0d84c95
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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