Water → 1-{1-[1-(2,6-Difluoro-benzoyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

HRID 729627Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 729627
Cl.[F:2][CH2:3][C:4]([C:8]1[CH:9]=[C:10]([NH:20][C:21]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([O:34][CH:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)=[N:26][CH:25]=2)=[O:22])[N:11]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[N:12]=1)([CH2:6][F:7])[CH3:5].[F:41][C:42]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:43]=1[C:44](Cl)=[O:45].C(N(CC)CC)C.O>ClCCl>[F:41][C:42]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:43]=1[C:44]([N:38]1[CH2:39][CH2:40][CH:35]([O:34][C:27]2[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:24]([NH:23][C:21]([NH:20][C:10]3[N:11]([C:13]4[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=4)[N:12]=[C:8]([C:4]([CH2:6][F:7])([CH3:5])[CH2:3][F:2])[CH:9]=3)=[O:22])=[CH:25][N:26]=2)[CH2:36][CH2:37]1)=[O:45]

Komponenten

6

Edukt 4

HCID 962WaterHCID 8471TriethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 690537531-[5-(2-Fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[1-(piperidin-4-yloxy)-isoquinolin-4-yl]-urea hydrochloride

Produkt 1

HCID 690550751-{1-[1-(2,6-Difluoro-benzoyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Stir 1-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[1-(piperidin-4-yloxy)-isoquinolin-4-yl]-urea hydrochloride (Preparation 37, 0.6 mmol, 0.3 g), 2,6-difluorobenzoyl chloride (0.6 mmol, 0.07 mL) and triethylamine (1.7 mmol, 0.2 mL) in 5 mL of dichloromethane at room temperature overnight. Add some water and extract in dichloromethane. Wash organic layer with saturated aq. sodium chloride. Dry over anhydrous sodium sulfate and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with hexanes/ethyl acetate as eluent (30%-70%). LCMS ES+(m/z) 675 [M+H].

Aufarbeitung

  1. extractionextract in dichloromethane
  2. dry with materialDry over anhydrous sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. washSubject residue to silica gel chromatography eluting with hexanes/ethyl acetate as eluent (30%-70%)

Quellen und Nachweise

ORD-Eintrag
ord-26eeb220cc1f4a39b9e5d2fe1f054241
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07582638B2

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