2-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → N-tert-butyl-2-(5-(difluoromethoxy)-1-(morpholin-2-ylmethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246510

Reaktionsgleichung

Reaktionsgleichung von HRID 246510
C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH:25]([F:27])[F:26])=[CH:21][CH:22]=3)[C:17]([C:28]3[N:29]=[C:30]4[C:36]([C:37]([NH:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:35][N:34]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:31]4=[N:32][CH:33]=3)=[N:16]2)[CH2:9]1)C1C=CC=CC=1.[H][H]>C(OCC)(=O)C.CO.[Pd]>[C:40]([NH:39][C:37]([C:36]1[C:30]2[C:31](=[N:32][CH:33]=[C:28]([C:17]3[C:18]4[C:23](=[CH:22][CH:21]=[C:20]([O:24][CH:25]([F:27])[F:26])[CH:19]=4)[N:15]([CH2:14][CH:10]4[O:11][CH2:12][CH2:13][NH:8][CH2:9]4)[N:16]=3)[N:29]=2)[N:34]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[CH:35]=1)=[O:38])([CH3:43])([CH3:42])[CH3:41]

Komponenten

6

Edukt 2

HCID 712796062-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 71279850N-tert-butyl-2-(5-(difluoromethoxy)-1-(morpholin-2-ylmethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirred solution of 2-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (see Example 340, 130 mg, 181 μmol) in ethyl acetate (2 mL) and methanol (1 mL) was added palladium on carbon (19.2 mg) and the mixture hydrogenated using a balloon filled with hydrogen gas. After stirring at room temperature for 15 h, the mixture was transferred to a Parr hydrogenator and shaken under 40 psi for 1 h. The mixture was filtered, concentrated in vacuo and then purified by chromatography (silica, 24 g Analogix column, 0-100% ethyl acetate in hexanes followed by 5% methanol in ethyl acetate) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(morpholin-2-ylmethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.10 g 88%). MS (M+H)+=630.

Aufarbeitung

  1. stirringshaken under 40 psi for 1 h
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated in vacuo
  4. custompurified by chromatography (silica, 24 g Analogix column, 0-100% ethyl acetate in hexanes followed by 5% methanol in ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-a1a950a4f90a47dd9bd5cc05fcccc9e7
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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