2-Chloropyridine → cis(+/-)-4-Chloro-N-(3-ethoxy-1-pyridin-2-ylpiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide

HRID 1425193Notes

Reaction equation

HRID 1425193 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].Cl[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(OCC)(=O)C>[Cl:2][C:3]1[N:4]=[C:5]([C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][N:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH2:15][C@H:14]2[O:19][CH2:20][CH3:21])=[O:11])[NH:6][C:7]=1[CH2:8][CH3:9]

Participants

6

Reactant 3

HCID 79772-ChloropyridineHCID 10340Sodium CarbonateHCID 86648665cis(+/-)-4-Chloro-N-(3-ethoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide hydrochloride

Product 1

HCID 86648667cis(+/-)-4-Chloro-N-(3-ethoxy-1-pyridin-2-ylpiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamideYield 3.5%

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), 2-chloropyridine (0.035 mL, 0.37 mmol) and sodium carbonate (157 mg, 1.48 mmol) were suspended in DMF (1 mL), and the suspension was heated using a microwave reactor at 180° C. for 30 minutes. The reaction solution was diluted with ethyl acetate, washed with 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: hexane/ethyl acetate=7/3→1/0) to obtain 3.9 mg of the title compound as a white amorphous solid (3%).

Workup

  1. temperaturethe suspension was heated
  2. customat 180° C.
  3. customfor 30 minutes
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentration under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=7/3→1/0)

Sources & evidence

ORD record
ord-ce65bd7e079f470283dc4d942f2ad71c
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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