반응 #1441

반응 방정식

t-butoxycarbonylglycine

1-hydroxybenztriazole

N-methylmorpholine

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride

4'-[(2-amino-5,6-dihydro-4H-thiazolo[5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrobromide

→

4'-[(2-glycylamino-5,6-dihydro-4H-thiazolo[5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide 2-propylalcohol hydrochloride

수율 55.7%

용매

water

dichloromethane

triethylamine

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONwas added to the resulting solution
2. 2
   workup.STIRRINGstirred for 60 minutes
3. 3
   온도To this reaction solution, again cooled on an ice bath
4. 4
   workup.DISSOLUTIONhad been dissolved
5. 5
   workup.STIRRINGstirring at room temperature
6. 6
   workup.STIRRINGstirred for 60 minutes
7. 7
   기타subjected to phase separation
8. 8
   기타The dichloromethane layer was separated
9. 9
   세척washed with a saturated sodium bicarbonate aqueous solution
10. 10
    건조a saturated sodium chloride aqueous solution once for each and then dried over anhydrous magnesium sulfate
11. 11
    기타After removing the solvent
12. 12
    workup.DISTILLATIONby distillation
13. 13
    온도With cooling on an ice bath
14. 14
    workup.ADDITIONthe suspension was mixed with 4.4 ml of 4N hydrochloric acid-dioxane
15. 15
    workup.STIRRINGstirred for 3 hours
16. 16
    농축Thereafter, the reaction solution was concentrated
17. 17
    기타the thus obtained residue was recrystallized from 2-propyl alcohol

실험 절차

After dissolving 176 mg of t-butoxycarbonylglycine, 205 mg of 1-hydroxybenztriazole and 0.15 ml of N-methylmorpholine in 3.5 ml of dichloromethane, 192 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added to the resulting solution with stirring on an ice bath, and the mixture was warmed up to room temperature and stirred for 60 minutes. To this reaction solution, again cooled on an ice bath, was added dropwise 4 ml of dichloromethane in which 400 mg of the 4'-[(2-amino-5,6-dihydro-4H-thiazolo[5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrobromide described in Example 1 and 0.103 ml of triethylamine had been dissolved, followed by overnight stirring at room temperature. The reaction solution was mixed with water, stirred for 60 minutes and then subjected to phase separation. The dichloromethane layer was separated, washed with a saturated sodium bicarbonate aqueous solution and a saturated sodium chloride aqueous solution once for each and then dried over anhydrous magnesium sulfate. After removing the solvent by distillation, the thus obtained residue was suspended in 3 ml of methyl alcohol. With cooling on an ice bath, the suspension was mixed with 4.4 ml of 4N hydrochloric acid-dioxane and stirred for 3 hours. Thereafter, the reaction solution was concentrated and the thus obtained residue was recrystallized from 2-propyl alcohol to obtain 250 mg of 4'-[(2-glycylamino-5,6-dihydro-4H-thiazolo[5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide 2-propylalcohol hydrochloride.

출처