反应详情

A solution of N-(2-aminoethyl)morpholine (170.5 g) in methyl isobutyl ketone (200 ml) was added portionwise to a solution of diketene (102 ml) in methyl isobutyl ketone (1.3 () at -30 to -10° C. under stirring and the mixture was stirred at -10 to 0° C. for one hour. To the resultant solution containing N-(2-morpholinoethyl)acetoacetamide, was added 3-(3-nitrophenyl)-1-phenyl-2-propen-1-one (220.4 g) and ammonium acetate (100 g) and the mixture was stirred at 80° C. for 4.5 hours. The reaction mixture was washed with water and dried over magnesium sulfate. To the filtrate containing 1,4-dihydro-3-(2-morpholinoethylcarbamoyl)-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine was added manganese dioxide (700 g) and the resultant mixture was stirred at 80° C. for 2 hours. Manganese dioxide was filtered off and the filtrate was evaporated in vacuo. A mixture of ethyl acetate and water was added to the residue and adjusted to pH 1.0 with 10% hydrochloric acid. The separated aqueous layer was adjusted to pH 9.0 with 20% aqueous potassium carbonate and extracted with a mixture of ethyl acetate and tetrahydrofuran. The extract was washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was recrystallized from ethanol to give 3-(2-morpholinoethylcarbamoyl)-2-methyl-4-(3-nitrophenyl)-6-phenylpyrid ine (154 g, yield 39.6 %), which was identified as the compound of Examples 9-(20 and 24-(3) by their physical data.

1. stirringthe mixture was stirred at -10 to 0° C. for one hour
2. stirringthe mixture was stirred at 80° C. for 4.5 hours
3. washThe reaction mixture was washed with water
4. dry with materialdried over magnesium sulfate
5. additionTo the filtrate containing 1,4-dihydro-3-(2-morpholinoethylcarbamoyl)-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine
6. additionwas added manganese dioxide (700 g)
7. stirringthe resultant mixture was stirred at 80° C. for 2 hours
8. filtrationManganese dioxide was filtered off
9. customthe filtrate was evaporated in vacuo
10. additionA mixture of ethyl acetate and water
11. additionwas added to the residue
12. extractionextracted with a mixture of ethyl acetate and tetrahydrofuran
13. washThe extract was washed with brine
14. dry with materialdried over magnesium sulfate
15. customThe solvent was evaporated in vacuo
16. customthe residue was recrystallized from ethanol