Oxamic Acid → cis(+/-)-N-{1-[Amino(oxo)acetyl]-3-ethoxypiperidin-4-yl}-4-chloro-5-ethyl-1H-imidazole-2-carboxamide

HRID 1425200Notes

Reaction equation

HRID 1425200 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

8

Reactant 5

HCID 974Oxamic AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86648665cis(+/-)-4-Chloro-N-(3-ethoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide hydrochloride

Product 1

HCID 86648675cis(+/-)-N-{1-[Amino(oxo)acetyl]-3-ethoxypiperidin-4-yl}-4-chloro-5-ethyl-1H-imidazole-2-carboxamideYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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

  1. washwashed with saturated aqueous sodium bicarbonate solution, water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentration under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=1/0→9/1)

Sources & evidence

ORD record
ord-06a6925ffa594b04aae63a42470c9bd6
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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