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

HRID 29426Notes

Reaction equation

HRID 29426 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[C:9]([CH3:15])=[C:10]([C:12]([OH:14])=O)[O:11][C:7]=2[CH:6]=[CH:5][C:4]=1[CH3:16].[C:17]([O:21][C:22](=[O:44])[C@@H:23]([NH:27][S:28]([C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([NH2:43])=[CH:39][CH:38]=2)=[CH:33][CH:32]=1)(=[O:30])=[O:29])[CH:24]([CH3:26])[CH3:25])([CH3:20])([CH3:19])[CH3:18].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>[Cl-].[Na+].O.CN(C=O)C>[C:17]([O:21][C:22](=[O:44])[C@@H:23]([NH:27][S:28]([C:31]1[CH:32]=[CH:33][C:34]([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:12]([C:10]3[O:11][C:7]4[CH:6]=[CH:5][C:4]([CH3:16])=[C:3]([O:2][CH3:1])[C:8]=4[C:9]=3[CH3:15])=[O:14])=[CH:41][CH:42]=2)=[CH:35][CH:36]=1)(=[O:30])=[O:29])[CH:24]([CH3:26])[CH3:25])([CH3:19])([CH3:20])[CH3:18]

Participants

7

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 687142664-Methoxy-3,5-dimethyl-benzofuran-2-carboxylic acid

Product 1

HCID 68713923(S)-2-{4'-[(4-methoxy-3,5-dimethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl esterYield 73.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 45 mg (0.2 mmol) of 4-methoxy-3,5-dimethyl-benzofuran-2-carboxylic acid was added 124 mg (1.5 eq) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester, BOP (106 mg, 1.2 eq), N,N-diisopropylethylamine (31 mg, 1.2 eq) and 2 mL of DMF. The mixture was stirred at room temperature for 24 h. Brine was added and the mixture was extracted with ethyl acetate. The combined organic solution was washed with 2N HCl and water. Removal of the solvent from the organic solution gave the crude product, which was purified by column chromatography on silica gel to give 89 mg of (S)-2-{4′-[(4-methoxy-3,5-dimethyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid tert-butyl ester as an off-white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic solution was washed with 2N HCl and water
  3. customRemoval of the solvent from the organic solution
  4. customgave the crude product, which
  5. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-8e777055c651430b8ebe438909546464
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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