Reaction equation
Cl.[Cl:2][C:3]1[N:4]=[C:5]([C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][NH:16][CH2:15][C@H:14]2[O:19][CH2:20][CH3:21])=[O:11])[NH:6][C:7]=1[CH2:8][CH3:9].[C:22](O)(=[O:26])[C:23]([NH2:25])=[O:24].CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C>[NH2:25][C:23](=[O:24])[C:22]([N:16]1[CH2:17][CH2:18][C@H:13]([NH:12][C:10]([C:5]2[NH:6][C:7]([CH2:8][CH3:9])=[C:3]([Cl:2])[N:4]=2)=[O:11])[C@H:14]([O:19][CH2:20][CH3:21])[CH2:15]1)=[O:26]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Procedure
cis(±)-4-Chloro-N-(3-ethoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide hydrochloride obtained in Example (131a) (100 mg, 0.297 mmol), oxamic acid (26 mg, 0.29 mmol) and WSC hydrochloride (120 mg, 0.626 mmol) were suspended in DMF (3 mL). Triethylamine (0.040 mL, 0.29 mmol) and HOBT (40 mg, 0.30 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate solution, water and brine, and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=1/0→9/1) to obtain 64.7 mg of the title compound as a colorless solid (59%).
Workup
- washwashed with saturated aqueous sodium bicarbonate solution, water and brine
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentration under reduced pressure
- customthe residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=1/0→9/1)
Sources & evidence
- ORD record
- ord-48b73818211a4154a2481f284e1ca2bc
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08536197B2
Linked notes
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