反应详情

温度

120 °C

A dry mixture of 1.8 parts of 2-chloro-1H-benzimidazole, 4.28 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 0.1 parts of potassium iodide was pulverized. A few drops of N,N-dimethylacetamide were added and the whole was stirred for 4 hours at 120° C. The reaction mixture was taken up in a mixture of water and dichloromethane. The whole was treated with ammonium hydroxide. The organic layer was separated, washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of acetonitrile and 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.06 parts (18.6%) of cis-4-amino-N-[1-[2-(1H-benzimidazol-2-ylamino)ethyl]-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide; mp. 205.8° C. (compound 28).

1. customThe organic layer was separated
2. washwashed with water
3. customdried
4. filtrationfiltered
5. customevaporated
6. customThe residue was purified by column chromatography over silica gel using
7. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
8. customThe pure fractions were collected
9. customthe eluent was evaporated
10. customThe residue was crystallized from a mixture of acetonitrile and 2,2'-oxybispropane
11. filtrationThe product was filtered off
12. customdried