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

HRID 29386Notes

Reaction equation

HRID 29386 reaction equation
[Cl: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].N1C=CC=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]([Cl: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 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 59847687(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl esterHCID 687142675-Chloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 68712004(S)-2-{4'-[(5-chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 80 mg (0.33 mmol) of 5-chloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 2 mL of oxalyl chloride and the mixture refluxed for 2 h, then stirred room temperature overnight. The excess oxalyl chloride was removed under vacuum. The residue was dissolved in 2 mL of dichloromethane and was added to a mixture of 181 mg (0.5 mmol) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester and 1 mL of pyridine in an ice/water bath. The mixture was stirred at 0° C. overnight. The reaction mixture was diluted with dichloromethane and was washed with 2N HCl, and water. Removal of the solvent in vacuo gave the crude product which was purified by column chromatography to give 168 mg (86% yield) of (S)-2-{4′-[(5-chloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as a white solid.

Workup

  1. temperaturethe mixture refluxed for 2 h
  2. customThe excess oxalyl chloride was removed under vacuum
  3. dissolutionThe residue was dissolved in 2 mL of dichloromethane
  4. stirringThe mixture was stirred at 0° C. overnight
  5. washwas washed with 2N HCl, and water
  6. customRemoval of the solvent in vacuo
  7. customgave the crude product which
  8. customwas purified by column chromatography

Sources & evidence

ORD record
ord-031d9ce06a43411e9353f5377657cf39
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

Loading…