反応 #1441

反応方程式

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

収率 55.7%

溶媒

water

dichloromethane

triethylamine

dichloromethane

反応条件

後処理

1. 1
   workup.ADDITIONwas added to the resulting solution
2. 2
   workup.STIRRINGstirred for 60 minutes
3. 3
   温度To 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
   その他subjected to phase separation
8. 8
   その他The dichloromethane layer was separated
9. 9
   洗浄washed with a saturated sodium bicarbonate aqueous solution
10. 10
    乾燥a saturated sodium chloride aqueous solution once for each and then dried over anhydrous magnesium sulfate
11. 11
    その他After removing the solvent
12. 12
    workup.DISTILLATIONby distillation
13. 13
    温度With 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
    濃縮Thereafter, the reaction solution was concentrated
17. 17
    その他the thus obtained residue was recrystallized from 2-propyl alcohol

実験手順

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.

出典