Diisopropylethylamine → (S)-2-{4'-[(5,7-dichloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl ester

HRID 29391Notes

Reaction equation

HRID 29391 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([Cl:17])[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:18]([O:22][C:23](=[O:45])[C@@H:24]([NH:28][S:29]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)=[CH:34][CH:33]=1)(=[O:31])=[O:30])[CH:25]([CH3:27])[CH3:26])([CH3:21])([CH3:20])[CH3:19].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:18]([O:22][C:23](=[O:45])[C@@H:24]([NH:28][S:29]([C:32]1[CH:33]=[CH:34][C:35]([C:38]2[CH:39]=[CH:40][C:41]([NH:44][C:10]([C:8]3[O:9][C:5]4[C:4]([Cl:17])=[CH:3][C:2]([Cl:1])=[C:14]([O:15][CH3:16])[C:6]=4[C:7]=3[CH3:13])=[O:12])=[CH:42][CH:43]=2)=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH:25]([CH3:27])[CH3:26])([CH3:20])([CH3:21])[CH3:19]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10525284(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl esterHCID 687160205,7-Dichloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 68714769(S)-2-{4'-[(5,7-dichloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 80 mg of 5,7-dichloro-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 120 mg of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester, 154 mg of BOP, 50 mg of N,N-diisopropylethylamine and 4 mL of DMF. The mixture was stirred at room temperature for 48 h. The mixture was washed with brine and was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine. Removal of the solvent in vacuo and purification of the residue by column chromatography on silica gel gave 110 mg (60% yield) of (S)-2-{4′-[(5,7-dichloro-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl ester as an off-white solid.

Workup

  1. washThe mixture was washed with brine
  2. extractionwas extracted with ethyl acetate
  3. washThe combined ethyl acetate layers were washed with brine
  4. customRemoval of the solvent
  5. customin vacuo and purification of the residue by column chromatography on silica gel

Sources & evidence

ORD record
ord-6aca8ed2c9774d81982081de1e92b443
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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