反应 #1446

反应方程式

water

phenyltrimethylammonium tribromide

tetrahydrofuran

4'-[(5-oxo-2,3,4,5-tetrahydro1H-1-benzazepin-1-yl)carbonyl]-2-isopropylbenzanilide

→

2-isopropoxy-4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]benzanilide

反应条件

后处理

1. 1
   温度With cooling on an ice bath
2. 2
   过滤Filtration
3. 3
   洗涤The filtered material was washed with tetrahydrofuran
4. 4
   浓缩concentrated
5. 5
   workup.DISSOLUTIONThe thus obtained residue was dissolved in chloroform
6. 6
   洗涤washed with a sodium bicarbonate aqueous solution
7. 7
   干燥dried over anhydrous magnesium sulfate
8. 8
   workup.DISTILLATIONAfter distilling off the solvent
9. 9
   其他the residue was further evaporated to dryness
10. 10
    workup.DISSOLUTIONThe thus obtained solid substance was dissolved in 40 ml of chloroform
11. 11
    workup.ADDITIONthe resulting solution was mixed with 1.11 g of acetamidine hydrochloride and 2.26 g of potassium carbonate
12. 12
    workup.WAITsubjected to 20 hours
13. 13
    温度of heating
14. 14
    温度under reflux in a stream of argon
15. 15
    其他The resulting reaction solution
16. 16
    其他phase separation
17. 17
    其他the organic layer was separated
18. 18
    干燥dried over anhydrous magnesium sulfate
19. 19
    其他After removing the solvent
20. 20
    workup.DISTILLATIONby distillation under a reduced pressure
21. 21
    其他the thus obtained residue was crystallized from toluene

实验过程

With cooling on an ice bath, a 793 mg portion of phenyltrimethylammonium tribromide was added to 20 ml of tetrahydrofuran solution containing 1.0 g of 4'-[(5-oxo-2,3,4,5-tetrahydro1H-1-benzazepin-1-yl)carbonyl]-2-isopropylbenzanilide, and the mixture was warmed up to room temperature. Filtration was carried out when disappearance of the color of bromine was confirmed after about 60 minutes. The filtered material was washed with tetrahydrofuran, and the filtrates were combined and concentrated. The thus obtained residue was dissolved in chloroform, washed with a sodium bicarbonate aqueous solution and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was further evaporated to dryness using a vacuum pump. The thus obtained solid substance was dissolved in 40 ml of chloroform, and the resulting solution was mixed with 1.11 g of acetamidine hydrochloride and 2.26 g of potassium carbonate and subjected to 20 hours of heating under reflux in a stream of argon. The resulting reaction solution was mixed with water to effect phase separation, and the organic layer was separated and dried over anhydrous magnesium sulfate. After removing the solvent by distillation under a reduced pressure, the thus obtained residue was crystallized from toluene to obtain 640 mg of 2-isopropoxy-4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]benzanilide. A 563 mg portion of this compound was dissolved in 5.5 ml of ethyl alcohol, mixed with 0.45 ml of 4N hydrochloric acid-ethyl acetate and recrystallized to obtain 400 mg of 2-isopropyl-4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]benzanilide hydrochloride.

来源