Triethylamine → 1-(4-Benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide

HRID 1715094Notes

Reaction equation

HRID 1715094 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:19]([CH3:20])=[C:18]([C:21](O)=[O:22])[N:17]=[C:16]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:45][N:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1>C(Cl)Cl.CN(C=O)C.O>[N:46]1([NH:45][C:21]([C:18]2[N:17]=[C:16]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=3[Cl:31])[N:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:10][CH:11]=3)[C:19]=2[CH3:20])=[O:22])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 166581-AminopiperidineHCID 65578Oxalyl chlorideHCID 594655061-(4-Benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid

Product 1

HCID 114895171-(4-Benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamideYield 74%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(4-benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid, from Ex 1, Step 3 (3.38 g, 7.5 mmol) in 60 ml CH2Cl2 was added 3 drops of DMF followed by oxalyl chloride (1.3 ml, 14.9 mmol). The mixture was refluxed for 2 hours, cooled to room temperature and evaporated to dryness. The residue was dissolved in 50 ml CH2Cl2 and cooled to 0° C. Triethylamine (2.1 ml, 14.9 mmol) was added followed by 1-aminopiperidine (0.9 ml, 8.2 mmol) and the mixture was stirred at room temperature for 2 hours. Water (300 ml) was added, the mixture extracted with CH2Cl2 (3×100 ml), dried (Na2SO4), filtered and concentrated. Flash chromatography (silica, hexane:EtOAc 1:2, EtOAc) afforded 2.94 g (74%) of the title compound as a white solid.

Workup

  1. temperatureThe mixture was refluxed for 2 hours
  2. customevaporated to dryness
  3. dissolutionThe residue was dissolved in 50 ml CH2Cl2
  4. temperaturecooled to 0° C
  5. extractionthe mixture extracted with CH2Cl2 (3×100 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d1280e26f602442c933a46f72d03aba3
Source dataset
uspto-grants-2010_09
Patent number
US07799804B2

Reaction notes

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