5-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one → N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]ethyl}-4-fluoro-2-nitrobenzamide hydrochloride

HRID 437671Notes

Reaction equation

HRID 437671 reaction equation
Br[CH2:2][CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[N+:13]([O-:15])=[O:14].[Cl:17][C:18]1[CH:33]=[CH:32][C:21]2[N:22]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[C:23](=[O:25])[NH:24][C:20]=2[CH:19]=1>CN(C)C=O>[ClH:17].[Cl:17][C:18]1[CH:33]=[CH:32][C:21]2[N:22]([CH:26]3[CH2:27][CH2:28][N:29]([CH2:2][CH2:3][NH:4][C:5](=[O:16])[C:6]4[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=4[N+:13]([O-:15])=[O:14])[CH2:30][CH2:31]3)[C:23](=[O:25])[NH:24][C:20]=2[CH:19]=1

Participants

4

Reactant 2

HCID 1046075-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 21428900N-(2-bromoethyl)-4-fluoro-2-nitrobenzamide

Product 1

HCID 21428973N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]ethyl}-4-fluoro-2-nitrobenzamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 16 parts of N-(2-bromoethyl)-4-fluoro-2-nitrobenzamide, 12.6 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one and 216 parts of N,N-dimethylformamide is stirred and refluxed for 3 hours. The N,N-dimethylformamide is evaporated and the residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the hydrochloride salt in 2-propanone and 2-propanol. The salt is filtered off and crystallized from methanol, yielding 1.5 parts of N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]ethyl}-4-fluoro-2-nitrobenzamide hydrochloride; mp. 276.8° C.

Workup

  1. temperaturerefluxed for 3 hours
  2. customThe N,N-dimethylformamide is evaporated
  3. customthe residue is purified by column-chromatography over silica gel using
  4. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  5. customThe pure fractions are collected
  6. customthe eluent is evaporated
  7. filtrationThe salt is filtered off
  8. customcrystallized from methanol

Sources & evidence

ORD record
ord-011a9ccc0bfb4195b26254429f9f1a0b
Source dataset
uspto-grants-1977_06
Patent number
US04031226

Reaction notes

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