Water → N-(1-methyl-4-piperidinyl)-1-(2-pyrazinylmethyl)-1H-benzimidazol-2-amine

HRID 1084760Notes

Reaction equation

HRID 1084760 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[NH:13][C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[N:10]=2)[CH2:4][CH2:3]1.[H-].[Na+].Cl[CH2:21][C:22]1[CH:27]=[N:26][CH:25]=[CH:24][N:23]=1.O>CN(C)C=O>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[N:10]([CH2:21][C:22]3[CH:27]=[N:26][CH:25]=[CH:24][N:23]=3)[C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 170169Pyrazine, 2-(chloromethyl)-HCID 14677578(1H-Benzoimidazol-2-yl)-(1-methyl-piperidin-4-yl)-amine

Product 1

HCID 14677579N-(1-methyl-4-piperidinyl)-1-(2-pyrazinylmethyl)-1H-benzimidazol-2-amineYield 9.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred mixture of 11.5 parts of N-(1-methyl-4-piperidinyl)-1H-benzimidazol-2-amine and 144 parts of N,N-dimethylformamide was added 5 parts of a sodium hydride dispersion 50%. AFter stirring for 1 hour at room temperature, a solution of 12.8 parts of 2-(chloromethyl)pyrazine in N,N-dimethylformamide was added dropwise to the thus obtained mixture. Upon complete addition, stirring was continued for 2 hours at 50° C. The reaction mixture was poured into water and 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 was collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 1.5 parts (9.3%) of N-(1-methyl-4-piperidinyl)-1-(2-pyrazinylmethyl)-1H-benzimidazol-2-amine; mp. 169.3° C. (compound 69).

Workup

  1. additionUpon complete addition
  2. stirringstirring
  3. waitwas continued for 2 hours at 50° C
  4. extractionthe product was extracted with trichloromethane
  5. customThe extract was dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol
  10. customThe pure fractions was collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from acetonitrile
  13. filtrationThe product was filtered off
  14. customdried

Sources & evidence

ORD record
ord-6ee20f44956c432597216d15050132c1
Source dataset
uspto-grants-1991_04
Patent number
US05006527

Reaction notes

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