Reaktion #1446

Reaktionsgleichung

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

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturWith cooling on an ice bath
2. 2
   FiltrationFiltration
3. 3
   WaschenThe filtered material was washed with tetrahydrofuran
4. 4
   Einengenconcentrated
5. 5
   workup.DISSOLUTIONThe thus obtained residue was dissolved in chloroform
6. 6
   Waschenwashed with a sodium bicarbonate aqueous solution
7. 7
   Trocknendried over anhydrous magnesium sulfate
8. 8
   workup.DISTILLATIONAfter distilling off the solvent
9. 9
   Sonstigethe 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
    Temperaturof heating
14. 14
    Temperaturunder reflux in a stream of argon
15. 15
    SonstigeThe resulting reaction solution
16. 16
    Sonstigephase separation
17. 17
    Sonstigethe organic layer was separated
18. 18
    Trocknendried over anhydrous magnesium sulfate
19. 19
    SonstigeAfter removing the solvent
20. 20
    workup.DISTILLATIONby distillation under a reduced pressure
21. 21
    Sonstigethe thus obtained residue was crystallized from toluene

Vorschrift

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.

Quelle