Oxalyl chloride → (S)-2-{4'-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester

HRID 29396Notes

Reaction equation

HRID 29396 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]([OH:12])=O)=[C:7]([CH3:13])[C:6]=2[C:14]=1[O:15][CH3:16].C(Cl)(=O)C(Cl)=O.[CH3:23][O:24][C:25](=[O:47])[C@@H:26]([NH:30][S:31]([C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][C:43]([NH2:46])=[CH:42][CH:41]=2)=[CH:36][CH:35]=1)(=[O:33])=[O:32])[CH:27]([CH3:29])[CH3:28]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:23][O:24][C:25](=[O:47])[C@@H:26]([NH:30][S:31]([C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:41]=[CH:42][C:43]([NH:46][C:10]([C:8]3[O:9][C:5]4[CH:4]=[CH:3][C:2]([Br:1])=[C:14]([O:15][CH3:16])[C:6]=4[C:7]=3[CH3:13])=[O:12])=[CH:44][CH:45]=2)=[CH:36][CH:35]=1)(=[O:33])=[O:32])[CH:27]([CH3:29])[CH3:28]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 59847687(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl esterHCID 687165365-Bromo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 68714742(S)-2-{4'-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl esterYield 23%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To 40 mg (0.14 mmol) of 5-bromo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 0.5 mL of oxalyl chloride and the mixture was refluxed for 2 h, then the excess oxalyl chloride was removed by vacuum. The residue was dissolved in 0.5 mL of dichloromethane and was added to a mixture of 92 mg (0.25 mmol) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, 34 mg (0.28 mmol) of 4-(dimethylamino)pyridine and 1 mL of dichloromethane in an ice/water bath. The mixture was stirred at 0° C. for overnight. The mixture was diluted with dichloromethane and was washed with 2N HCl, and water. Removal of the solvent from the organic solution gave 20 mg (23% yield) of (S)-2-{4′-[(5-bromo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as an off-white solid.

Workup

  1. temperaturethe mixture was refluxed for 2 h
  2. customthe excess oxalyl chloride was removed by vacuum
  3. dissolutionThe residue was dissolved in 0.5 mL of dichloromethane
  4. washwas washed with 2N HCl, and water
  5. customRemoval of the solvent from the organic solution

Sources & evidence

ORD record
ord-8afaa50683ee4880b6d44dcbc0d3677d
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

Loading…