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

HRID 330549Notes

Reaction equation

HRID 330549 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 were 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 were 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 were 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-360f516f7c88449a9c923c936a9ba500
Source dataset
uspto-grants-1990_01
Patent number
US04897401

Reaction notes

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