Imidazole → N-(3,5-bis-Trifluoromethyl-benzyl)-6-(4-formyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamide

HRID 379398

Reaction equation

HRID 379398 reaction equation
CN(C)[CH:3]=[O:4].N1C=CN=C1.[F:11][C:12]([F:48])([F:47])[C:13]1[CH:14]=[C:15]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[CH2:16][N:17]([CH3:39])[C:18](=[O:38])[C:19]1[C:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])=[CH:23][C:22]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[N:21][CH:20]=1>>[F:48][C:12]([F:47])([F:11])[C:13]1[CH:14]=[C:15]([CH:40]=[C:41]([C:43]([F:45])([F:46])[F:44])[CH:42]=1)[CH2:16][N:17]([CH3:39])[C:18](=[O:38])[C:19]1[C:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])=[CH:23][C:22]([N:32]2[CH2:33][CH2:34][N:35]([CH:3]=[O:4])[CH2:36][CH2:37]2)=[N:21][CH:20]=1

Participants

4

Reactant 3

HCID 795ImidazoleHCID 6228DimethylformamideHCID 10280286N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-piperazin-1-yl-4-o-tolyl-nicotinamide

Product 1

HCID 9807991N-(3,5-bis-Trifluoromethyl-benzyl)-6-(4-formyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamideYield 82%

Conditions

Temperature
0 °C

Procedure

To a mixture of 0.089 ml (1.1 mmol) N,N-dimethylformamide and 38 mg (0.56 mmol) imidazole 0.071 ml (0.56 mmol) trimethylchlorosilane were added dropwise at room temperature. The reaction mixture was cooled to 0° C., and 0.10 g (0.19 mmol) N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-piperazin-1-yl-4-o-tolyl-nicotinamide (Example 53) were added. The ice-water bath was removed and the mixture stirred over night. The reaction was quenched with a mixture of 2 ml 1 N aqueous hydrochloric acid solution and 4 ml water, and the mixture was extracted with ethyl acetate. The combined extracts were dried with sodium sulfate and concentrated. Flash column chromatography afforded 81 mg (82%) of the title compound as a white solid.

Workup

  1. additionwere added dropwise at room temperature
  2. customThe ice-water bath was removed
  3. customThe reaction was quenched with a mixture of 2 ml 1 N aqueous hydrochloric acid solution and 4 ml water
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe combined extracts were dried with sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-47230032c92546e685ec29ac9eb80990
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Linked notes

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