反应详情

To a stirred mixture of 2.1 parts of 3-amino-2-pyrazinecarboxylic acid, 2.8 parts of N,N-dibutylbutanamine and 195 parts of dichloromethane were added 3.83 parts of 2-chloro-1-methylpyridinium iodide. After stirring for 15 minutes at room temperature, 5.5 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine were added and stirring was continued for one hour. The reaction mixture was washed with water, dried, filtered and evaporated. The residue was stirred in 2,2'-oxybispropane. The latter was decanted and the residue was purified by column-chromatography over slica gel using a mixture of trichloromethane and methanol (96:4 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 1,1'-oxybisethane, yielding 2.8 parts (38%) of 3-amino-N-[2-[4-[[1-[(4-fluorophenyl)-methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-2-pyrazinecarboxamide; mp. 156.9° C. (compound 113).

1. stirringstirring
2. waitwas continued for one hour
3. washThe reaction mixture was washed with water
4. customdried
5. filtrationfiltered
6. customevaporated
7. stirringThe residue was stirred in 2,2'-oxybispropane
8. customThe latter was decanted
9. customthe residue was purified by column-chromatography over slica gel
10. additiona mixture of trichloromethane and methanol (96:4 by volume) as eluent
11. customThe pure fractions were collected
12. customthe eluent was evaporated
13. customThe residue was crystallized from 1,1'-oxybisethane