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

HRID 29354Notes

Reaction equation

HRID 29354 reaction equation
[CH:1]([O:4][C:5]1[C:10]2[C:11]([CH3:17])=[C:12]([C:14]([OH:16])=O)[O:13][C:9]=2[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[CH3:18][O:19][C:20](=[O:42])[C@@H:21]([NH:25][S:26]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=2)=[CH:31][CH:30]=1)(=[O:28])=[O:27])[CH:22]([CH3:24])[CH3:23].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.[Cl-].[Na+].O>[CH3:18][O:19][C:20](=[O:42])[C@@H:21]([NH:25][S:26]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:14]([C:12]3[O:13][C:9]4[CH:8]=[CH:7][CH:6]=[C:5]([O:4][CH:1]([CH3:2])[CH3:3])[C:10]=4[C:11]=3[CH3:17])=[O:16])=[CH:39][CH:40]=2)=[CH:31][CH:30]=1)(=[O:28])=[O:27])[CH:22]([CH3:24])[CH3:23]

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 687160934-Isopropoxy-3-methyl-benzofuran-2-carboxylic acid

Product 1

HCID 68710039(S)-2-{4'-[(4-Isopropoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl esterYield 75.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 200 mg (0.91 mmol) 4-isopropoxy-3-methyl-benzofuran-2-carboxylic acid in 4 mL of DMF was added 329 mg (1 eq) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, 482 mg (1.2 eq) of BOP, and 0.19 mL of N,N-diisopropylethylamine. The mixture was stirred at room temperature overnight. Brine was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and water. Removal of the solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 395 mg (69% yield) of (S)-2-{4′-[(4-Isopropoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl ester as colorless oil.

Workup

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

Sources & evidence

ORD record
ord-1a2e99e69294420f9c8661260d712e8b
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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