Dimethylformamide → 1-[(4-fluorophenyl)methyl]-N-[1-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine

HRID 280341Notes

Reaction equation

HRID 280341 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.Cl.Cl.Cl[CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([NH:18][C:19]2[N:23]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:22]3[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=3[N:20]=2)[CH2:14][CH2:13]1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>O>[F:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][N:23]2[C:22]3[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=3[N:20]=[C:19]2[NH:18][CH:15]2[CH2:14][CH2:13][N:12]([CH2:11][CH2:10][N:3]3[CH:4]=[CH:5][N:6]=[C:2]3[CH3:1])[CH2:17][CH2:16]2)=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 127492-MethylimidazoleHCID 12891728N-[1-(2-chloroethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine dihydrochloride

Product 1

HCID 136538941-[(4-fluorophenyl)methyl]-N-[1-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amineYield 30%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1.64 parts of 2-methyl-1H-imidazole, 9.2 parts of N-[1-(2-chloroethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine dihydrochloride, 6.4 parts of sodium carbonate and 135 parts of N,N-dimethylformamide was stirred overnight at 60° C. The reaction mixture was poured into water. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (96:4 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 2.6 parts (30% of 1-[(4-fluorophenyl)methyl]-N-[1-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine; mp. 170.5° C. (compound 20).

Workup

  1. extractionThe product was extracted with trichloromethane
  2. customThe extract was dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was crystallized from acetonitrile
  10. filtrationThe product was filtered off
  11. customdried

Sources & evidence

ORD record
ord-cd476a63fb6f42aeb95fc88fcaf06a1c
Source dataset
uspto-grants-1986_05
Patent number
US04588722

Reaction notes

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