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

HRID 29405Notes

Reaction equation

HRID 29405 reaction equation
[I: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].[CH3:17][O:18][C:19](=[O:41])[C@@H:20]([NH:24][S:25]([C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:39]=[CH:38][C:37]([NH2:40])=[CH:36][CH:35]=2)=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH:21]([CH3:23])[CH3:22].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>[CH3:17][O:18][C:19](=[O:41])[C@@H:20]([NH:24][S:25]([C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:35]=[CH:36][C:37]([NH:40][C:10]([C:8]3[O:9][C:5]4[CH:4]=[CH:3][C:2]([I:1])=[C:14]([O:15][CH3:16])[C:6]=4[C:7]=3[CH3:13])=[O:12])=[CH:38][CH:39]=2)=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH:21]([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59847687(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl esterHCID 687173935-Iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 68716706(S)-2-{4'-[(5-iodo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl esterYield 47.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 110 mg (0.33 mmol) of 5-iodo-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 132 mg (1.1 eq) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, BOP (34 mg, 1.2 eq), N,N-diisopropylethylamine (52 mg, 1.2 eq) and 4 mL of DMF. The mixture was stirred at room temperature for 48 h. Brine was added and the mixture was extracted with ethyl acetate. The combined organic solution was washed with 2N HCl and water. Concentration of the organics in vacuo gave the crude product which was purified by column chromatography on silica gel to give 106 mg (47% yield) of (S)-2-{4′-[(5-iodo-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester was obtained 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. customConcentration of the organics in vacuo gave the crude product which
  4. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-5093750376804b70af63cd4893f005d5
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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