Dimethylformamide → (S)-2-(4'-{[5-(1-chloro-vinyl)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester

HRID 29412Notes

Reaction equation

HRID 29412 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:11][C:10]([C:12]([OH:14])=O)=[C:9]([CH3:15])[C:8]=2[C:16]=1[O:17][CH3:18])(=O)[CH3:2].C(Cl)(=O)C([Cl:22])=O.CN(C=O)C.[CH3:30][O:31][C:32](=[O:54])[C@@H:33]([NH:37][S:38]([C:41]1[CH:46]=[CH:45][C:44]([C:47]2[CH:52]=[CH:51][C:50]([NH2:53])=[CH:49][CH:48]=2)=[CH:43][CH:42]=1)(=[O:40])=[O:39])[CH:34]([CH3:36])[CH3:35]>N1C=CC=CC=1>[CH3:30][O:31][C:32](=[O:54])[C@@H:33]([NH:37][S:38]([C:41]1[CH:46]=[CH:45][C:44]([C:47]2[CH:48]=[CH:49][C:50]([NH:53][C:12]([C:10]3[O:11][C:7]4[CH:6]=[CH:5][C:4]([C:1]([Cl:22])=[CH2:2])=[C:16]([O:17][CH3:18])[C:8]=4[C:9]=3[CH3:15])=[O:14])=[CH:51][CH:52]=2)=[CH:43][CH:42]=1)(=[O:40])=[O:39])[CH:34]([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 59847687(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl esterHCID 687121675-Acetyl-4-methoxy-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 86642080(S)-2-(4'-{[5-(1-chloro-vinyl)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl esterYield 20%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To 75 mg (0.3 mmol) of 5-acetyl-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 1 mL of oxalyl chloride and the mixture was refluxed for 2.5 h in the presence of a catalytic amount of DMF, then the excess oxalyl chloride was removed under vacuum. The residue was dissolved in 1 mL of dichloromethane and was added to a mixture of 163 mg (0.46 mmol) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 2 mL of pyridine in an ice/water bath. The mixture was stirred at room temperature overnight. All the solvents were removed under vacuum. Column chromatography on silica gel gave 36 mg (20% yield) of (S)-2-(4′-{[5-(1-chloro-vinyl)-4-methoxy-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester as an off-white solid.

Workup

  1. customthe excess oxalyl chloride was removed under vacuum
  2. dissolutionThe residue was dissolved in 1 mL of dichloromethane
  3. customAll the solvents were removed under vacuum

Sources & evidence

ORD record
ord-9463b83cb9b04b5692bc8340ddd7a5fa
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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