反应详情

A mixture of 2-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide (0.54 g, 1.36 mmol), prepared as in Example 21, and sodium cyanide (0.33 g, 6.8 mmol) in 12 mL of DMSO was heated at reflux for 14 hours and then diluted with water and extracted twice with diethyl ether. The aqueous layer was extracted twice with methylene chloride and the combined methylene chloride layers were washed with water and brine, dried (MgSO4), filtered and concentrated. The residue was purified on silica gel by column chromatography eluting with 8% methanol/methylene chloride to give 2-{3-[4-(2-hydroxyphenyl)-piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide (0.134 g, 0.35 mmol) as an oil. The free base was recrystallized from a solution of fumaric acid in alcohol to give di(2-{3-[4-(2-hydroxyphenyl)-piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide) fumarate, m.p. 185°-186° C. Anal.: Calcd. for C21H30N5O2.(C4H4O4)0.5 : C, 62.57; H, 7.08; N, 15.86; Found: C, 62.44H, 7.08; N, 15.73%.

1. temperaturewas heated
2. temperatureat reflux for 14 hours
3. extractionextracted twice with diethyl ether
4. extractionThe aqueous layer was extracted twice with methylene chloride
5. washthe combined methylene chloride layers were washed with water and brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified on silica gel by column chromatography
10. washeluting with 8% methanol/methylene chloride