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 729627Notes

Reaction equation

HRID 729627 reaction equation
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]

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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].

Workup

  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%)

Sources & evidence

ORD record
ord-26eeb220cc1f4a39b9e5d2fe1f054241
Source dataset
uspto-grants-2009_09
Patent number
US07582638B2

Reaction notes

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