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

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.

1. additionwas added to the resulting solution
2. stirringstirred for 60 minutes
3. temperatureTo this reaction solution, again cooled on an ice bath
4. dissolutionhad been dissolved
5. stirringstirring at room temperature
6. stirringstirred for 60 minutes
7. customsubjected to phase separation
8. customThe dichloromethane layer was separated
9. washwashed with a saturated sodium bicarbonate aqueous solution
10. dry with materiala saturated sodium chloride aqueous solution once for each and then dried over anhydrous magnesium sulfate
11. customAfter removing the solvent
12. distillationby distillation
13. temperatureWith cooling on an ice bath
14. additionthe suspension was mixed with 4.4 ml of 4N hydrochloric acid-dioxane
15. stirringstirred for 3 hours
16. concentrationThereafter, the reaction solution was concentrated
17. customthe thus obtained residue was recrystallized from 2-propyl alcohol

ORD 기록

ord-52eeeb285aa44f2a8df38cb2bd9296be

출처 데이터셋

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05723606