1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-{(2S,3S)-2-[2-tert-butoxycarbonylamino-2-(4-methylsulfanyl-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

HRID 32834

反応式

HRID 32834 の反応式
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:22])[C@@H:12]([NH2:21])[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[S:8][CH:9]=1)=[O:4].[C:23]([O:27][C:28]([NH:30][CH:31]([C:35]1[CH:40]=[CH:39][C:38]([S:41][CH3:42])=[CH:37][CH:36]=1)[C:32](O)=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24].Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:22])[C@@H:12]([NH:21][C:32](=[O:33])[CH:31]([NH:30][C:28]([O:27][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:29])[C:35]2[CH:40]=[CH:39][C:38]([S:41][CH3:42])=[CH:37][CH:36]=2)[C@H:13]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:14])[S:8][CH:9]=1)=[O:4]

参加物

5

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 164463282-{[(Tert-butoxy)carbonyl]amino}-2-[4-(methylsulfanyl)phenyl]acetic acidHCID 86603390(2S,3S)-2-(2-amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester

生成物 1

HCID 866033942-{(2S,3S)-2-[2-tert-butoxycarbonylamino-2-(4-methylsulfanyl-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester収率 80%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 2-((2S,3S)-2-amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester (75 mg, 0.24 mmol) and tert-butoxycarbonylamino-(4-methylsulfanyl-phenyl)-acetic acid (77 mg, 0.26 mmol) in dichloromethane (10 mL) at 0° C. was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (50 mg, 0.26 mmol). The reaction was allowed to slowly warm to room temperature and stirred for 60 hours. The mixture was then partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over silica gel gradient eluted up to 7:3 ethyl acetate/hexane. The material obtained after chromatography was further treated by precipitation of dichloromethane solution with excess of hexanes to give 2-{(2S,3S)-2-[2-tert-butoxycarbonylamino-2-(4-methylsulfanyl-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester as a white amorphous solid (115 mg, 80%).

後処理

  1. customThe mixture was then partitioned between ethyl acetate and water
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography over silica gel gradient
  6. washeluted up to 7:3 ethyl acetate/hexane
  7. customThe material obtained after chromatography

出典と根拠

ORDレコード
ord-bc25aa330f8144e98799bfcab077e53d
出典データセット
uspto-grants-2008_09
特許番号
US07427635B2

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