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

HRID 342306

反应方程式

HRID 342306 反应方程式
[C:1]([O:5]C([NH:8][CH2:9][C:10](O)=[O:11])=O)(C)([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[ClH:30].C(N=C=NCCCN(C)C)C.Br.[NH2:43][C:44]1[S:45][C:46]2[CH2:47][CH2:48][N:49]([C:58]([C:60]3[CH:80]=[CH:79][C:63]([NH:64][C:65](=[O:78])[C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][C:67]=4[C:72]4[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=4)=[CH:62][CH:61]=3)=[O:59])[C:50]3[CH:57]=[CH:56][CH:55]=[CH:54][C:51]=3[C:52]=2[N:53]=1>ClCCl.O.C(N(CC)CC)C>[ClH:30].[CH3:2][CH:1]([OH:5])[CH3:3].[NH2:8][CH2:9][C:10]([NH:43][C:44]1[S:45][C:46]2[CH2:47][CH2:48][N:49]([C:58]([C:60]3[CH:80]=[CH:79][C:63]([NH:64][C:65](=[O:78])[C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][C:67]=4[C:72]4[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=4)=[CH:62][CH:61]=3)=[O:59])[C:50]3[CH:57]=[CH:56][CH:55]=[CH:54][C:51]=3[C:52]=2[N:53]=1)=[O:11]

参与物

9

反应物 5

HCID 7972N-甲基吗啉HCID 757711-羟基苯并三唑(HOBT)HCID 78288BOC-甘氨酸HCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐HCID 867521854'-[(2-amino-5,6-dihydro-4H-thiazolo(5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrobromide

产物 1

HCID 867521844'-[(2-glycylamino-5,6-dihydro-4H-thiazolo[5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide 2-propylalcohol hydrochloride收率 55.7%

试剂、催化剂与溶剂 3

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6344二氯甲烷溶剂2 次HCID 8471三乙胺溶剂

实验过程

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.

后处理

  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

来源与证据

ORD记录
ord-2d714f6d1da6477a867775557d7884df
来源数据集
uspto-grants-1999_01
专利号
US05856564

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