反应详情

A mixture of 2.2 parts of 3-bromo-1-propanamine hydrobromide, 4.1 parts of 1-[(4-fluorophenyl)methyl]-N-[1-(2-isothiocyanatoethyl)-4-piperidinyl]-1H-benzimidazol-2-amine, 2.2 parts of sodium carbonate and 135 parts of tetrahydrofuran was stirred overnight at room temperature. The reaction mixture was further stirred and refluxed for 3 hours. The mixture was filtered and the filtrate was evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume), saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 2.5 parts of 1-[(4-fluorophenyl)methyl]-N-[1-[2-[(5,6-dihydro-4H-1,3-thiazin-2-yl)amino]ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine monohydrate; mp. 121.4° C. (compound 117).

1. stirringThe reaction mixture was further stirred
2. temperaturerefluxed for 3 hours
3. filtrationThe mixture was filtered
4. customthe filtrate was evaporated
5. customThe residue was purified by column-chromatography over silica gel using
6. additiona mixture of trichloromethane and methanol (95:5 by volume)
7. customThe pure fractions were collected
8. customthe eluent was evaporated
9. customThe residue was crystallized from acetonitrile