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

HRID 1345

反応式

HRID 1345 の反応式
[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]

参加物

9

反応物 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867521854'-[(2-amino-5,6-dihydro-4H-thiazolo(5,4-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrobromide

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8471Triethylamine溶媒

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.

後処理

  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

出典と根拠

ORDレコード
ord-52eeeb285aa44f2a8df38cb2bd9296be
出典データセット
uspto-grants-1998_03
特許番号
US05723606

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