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

Reaction equation

HRID 32839 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-d1458445241b4463a8be4d1ed0ba9df1
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Linked notes

Loading…