Dimethylformamide → (S)-2-{4'-[(5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester

HRID 29415Notes

Reaction equation

HRID 29415 reaction equation
C(O[C:4]([C:6]1[O:7][C:8]2[CH:15]=[CH:14][C:13]([C:16](=[O:18])[CH3:17])=[C:12]([OH:19])[C:9]=2[C:10]=1[CH3:11])=[O:5])C.CCN=C=NCCCN(C)C.[CH3:31][O:32][C:33](=[O:55])[C@@H:34]([NH:38][S:39]([C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[CH:52][C:51]([NH2:54])=[CH:50][CH:49]=2)=[CH:44][CH:43]=1)(=[O:41])=[O:40])[CH:35]([CH3:37])[CH3:36].CN(C=O)C>[Cl-].[Na+].O>[CH3:31][O:32][C:33](=[O:55])[C@@H:34]([NH:38][S:39]([C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:49]=[CH:50][C:51]([NH:54][C:4]([C:6]3[O:7][C:8]4[CH:15]=[CH:14][C:13]([C:16](=[O:18])[CH3:17])=[C:12]([OH:19])[C:9]=4[C:10]=3[CH3:11])=[O:5])=[CH:52][CH:53]=2)=[CH:44][CH:43]=1)(=[O:41])=[O:40])[CH:35]([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 20205101Ethyl 5-acetyl-4-hydroxy-3-methylbenzofuran-2-carboxylateHCID 59847687(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester

Product 1

HCID 68716407(S)-2-{4'-[(5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl esterYield 11.5%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
65 °C

Procedure

To 70 mg (0.3 mmol) of 5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid ethyl ester was added 115 mg (2 eq) EDCI, 109 mg (1 eq) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2 mL of DMF. The mixture was stirred at 65° C. overnight. The reaction mixture was poured into brine, and extracted with dichloromethane. The organic solution was washed with 2N HCl and water. Removal of the solvents under vacuum gave crude product, which was purified by column chromatography on silica gel to give 20 mg (10% yield) of (S)-2-{4′-[(5-acetyl-4-hydroxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as a white solid.

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic solution was washed with 2N HCl and water
  3. customRemoval of the solvents under vacuum
  4. customgave crude product, which
  5. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-4716ed3695924c9493864b3bdc74a100
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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