反应详情

温度

120 °C

A mixture of 8.56 parts of 2-bromo-3-methylpyrazine and 0.1 parts of potassium iodide was pulverized and 2 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide were added. The whole was stirred for 3 hours at 120° C. The reaction mixture was taken up in dichloromethane and water and made alkaline 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 (95:5 by volume) as eluent. The first fractions was collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 1.95 parts (36%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-[(3-methyl-2-pyrazinyl)amino]ethyl]-4-piperidinyl]benzamide; mp. 169.5° C. (compound 27).

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 (95:5 by volume) as eluent
8. customThe first fractions was collected
9. customthe eluent was evaporated
10. customThe residue was crystallized from acetonitrile
11. filtrationThe product was filtered off
12. customdried