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

HRID 32839

반응식

HRID 32839 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:15][CH:14]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][O:28][C:29]([C:31]1[N:32]=[C:33]([NH:36][C:37](=[O:48])[C@@H:38]([NH2:47])[C@H:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH3:40])[S:34][CH:35]=1)=[O:30].Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:27][O:28][C:29]([C:31]1[N:32]=[C:33]([NH:36][C:37](=[O:48])[C@@H:38]([NH:47][C:10](=[O:11])[C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:13]2[CH:14]=[CH:15][C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])=[CH:17][CH:18]=2)[C@H:39]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH3:40])[S:34][CH:35]=1)=[O:30]

참가 물질

5

반응물 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13224269(R)-tert-butoxycarbonylamino-(4-tert-butoxycarbonylamino-phenyl)-acetic acidHCID 86603390(2S,3S)-2-(2-amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester

생성물 1

HCID 866033972-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester수율 82.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of (R)-tert-butoxycarbonylamino-(4-tert-butoxycarbonylamino-phenyl)-acetic acid (420 mg, 1.13 mmol) and (2S,3S)-2-(2-amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester (300 mg, 0.94 mmol) (prepared as described in Example 7) in dichloromethane (50 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (220 mg, 1.13 mmol) at 0° C. The reaction mixture was allowed to warm to ambient temperature slowly, stirred overnight and then partitioned between dichloromethane and water. The organic layer was dried over sodium sulfate, filtered and concentrated to give the crude product. Purification by chromatography over silica gel gradient eluted between 0 and 60% ethyl acetate in hexanes followed by a precipitation of the product from dichloromethane with excess hexanes gave 2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester as a white solid (520 mg, 82%).

후처리

  1. custompartitioned between dichloromethane and water
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product
  6. customPurification by chromatography over silica gel gradient
  7. washeluted between 0 and 60% ethyl acetate in hexanes
  8. customfollowed by a precipitation of the product from dichloromethane with excess hexanes

출처 및 근거

ORD 기록
ord-d1458445241b4463a8be4d1ed0ba9df1
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427635B2

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