1,4-Dioxane hydrochloride → methyl N-[(1S)-3-amino-1-[[(1S,2S)-1-benzyl-3-[(4R)-5,5-dimethyl-4-(o-tolylmethylcarbamoyl)thiazolidin-3-yl]-2-hydroxy-3-oxo-propyl]carbamoyl]-3-oxo-propyl]carbamate

HRID 1596328Notes

Reaction equation

HRID 1596328 reaction equation
Cl.O1CCOCC1.[CH3:8][C:9]1[CH:53]=[CH:52][CH:51]=[CH:50][C:10]=1[CH2:11][NH:12][C:13]([C@@H:15]1[C:19]([CH3:21])([CH3:20])[S:18][CH2:17][N:16]1[C:22](=[O:49])[C@@H:23]([OH:48])[C@@H:24]([NH:32][C:33](=[O:47])[C@H:34]([CH2:43][C:44](=[O:46])[NH2:45])[NH:35][C:36]([O:38][C:39](C)(C)C)=[O:37])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:14]>>[CH3:8][C:9]1[CH:53]=[CH:52][CH:51]=[CH:50][C:10]=1[CH2:11][NH:12][C:13]([C@@H:15]1[C:19]([CH3:21])([CH3:20])[S:18][CH2:17][N:16]1[C:22](=[O:49])[C@@H:23]([OH:48])[C@@H:24]([NH:32][C:33](=[O:47])[C@H:34]([CH2:43][C:44](=[O:46])[NH2:45])[NH:35][C:36]([O:38][CH3:39])=[O:37])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:14]

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 70249347(R)-N-(2-methylbenzyl)-3-{(2S,3S)-3-[N-(tert-butoxycarbonyl)-L-asparaginyl]amino-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide

Product 1

HCID 16727998methyl N-[(1S)-3-amino-1-[[(1S,2S)-1-benzyl-3-[(4R)-5,5-dimethyl-4-(o-tolylmethylcarbamoyl)thiazolidin-3-yl]-2-hydroxy-3-oxo-propyl]carbamoyl]-3-oxo-propyl]carbamateYield 22.9%

Procedure

4N HCl/dioxane (2 ml) was added to the compound Boc-Asn-Apns-Dmt-NHBzl(2-Me) (70 mg) obtained in the step 1 of Example 6 and the mixture was stirred for two hours. After concentration, the reaction mixture was dissolved in DMF (1 ml) and neutralized with triethylamine (15 μl). After the addition of methyl chloroformate (9 μl ) and triethylamine (16 μl), the mixture was stirred for two hours. After the addition of ethyl acetate, the reaction mixture was washed with 3% Na2CO3, 1N HCl, and 5% NaCl and dried over MgSO4. After filtration and concentration, the residue was purified using silica gel column chromatography to obtain the title compound (15 mg).

Workup

  1. customobtained in the step 1 of Example 6
  2. concentrationAfter concentration
  3. dissolutionthe reaction mixture was dissolved in DMF (1 ml)
  4. additionAfter the addition of methyl chloroformate (9 μl ) and triethylamine (16 μl)
  5. stirringthe mixture was stirred for two hours
  6. additionAfter the addition of ethyl acetate
  7. washthe reaction mixture was washed with 3% Na2CO3, 1N HCl, and 5% NaCl
  8. dry with materialdried over MgSO4
  9. filtrationAfter filtration and concentration
  10. customthe residue was purified

Sources & evidence

ORD record
ord-48749ed4492c49fca745404d32f8864a
Source dataset
uspto-grants-2001_09
Patent number
US06291432B1

Reaction notes

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