1,4-Dioxane hydrochloride → (R)-N-(2-Methylbenzyl)-3-{(2S,3S)-3-[N-(2-benzofurancarbonyl)-L-asparaginyl]amino-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide

HRID 1596319Notes

Reaction equation

HRID 1596319 reaction equation
Cl.[O:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[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(OC(C)(C)C)=O)[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]([CH3:20])([CH3:21])[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:7]([C:6]1[O:5][C:4]2[CH:3]=[CH:52][CH:53]=[CH:9][C:10]=2[CH:11]=1)=[O:2])[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=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 16727970(R)-N-(2-Methylbenzyl)-3-{(2S,3S)-3-[N-(2-benzofurancarbonyl)-L-asparaginyl]amino-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide

Procedure

4N HCl/dioxane (2 ml) was added to Boc-Asn-Apns-Dmt-NHBzl(2-Me) (197 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 (3 ml) and neutralized with Et3N (0.042 ml). 2-benzofurancarboxylic acid (54 mg), HOBt (45 mg), and EDC.HCl (69 mg) were added to this solution, and the mixture was stirred overnight. After the addition of ethyl acetate, the reaction mixture was washed with 3% NaHCO3, 1N HCl, and 5% NaCl and dried over MgSO4. After filtration and concentration, the residue was purified using silica gel column chromatography and reprecipitated from ethyl acetate/n-hexane to obtain the title compound (108 mg).

Workup

  1. customobtained in the step 1 of Example 6
  2. concentrationAfter concentration
  3. dissolutionthe reaction mixture was dissolved in DMF (3 ml)
  4. addition2-benzofurancarboxylic acid (54 mg), HOBt (45 mg), and EDC.HCl (69 mg) were added to this solution
  5. stirringthe mixture was stirred overnight
  6. additionAfter the addition of ethyl acetate
  7. washthe reaction mixture was washed with 3% NaHCO3, 1N HCl, and 5% NaCl
  8. dry with materialdried over MgSO4
  9. filtrationAfter filtration and concentration
  10. customthe residue was purified
  11. customreprecipitated from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-6ba1d2354a2c43b6b72a4a86668ea702
Source dataset
uspto-grants-2001_09
Patent number
US06291432B1

Reaction notes

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