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

HRID 29365Notes

Reaction equation

HRID 29365 reaction equation
[CH3:1][C:2]1[C:6]2[C:7]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:17]([OH:19])=O.[CH3:20][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].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>[CH3:20][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:38]=[CH:39][C:40]([NH:43][C:17]([C:3]3[O:4][C:5]4[CH:10]=[CH:9][CH:8]=[C:7]([C:11]5[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=5)[C:6]=4[C:2]=3[CH3:1])=[O:19])=[CH:41][CH:42]=2)=[CH:33][CH:32]=1)(=[O:30])=[O:29])[CH:24]([CH3:26])[CH3:25]

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 687125623-Methyl-4-pyridin-3-yl-benzofuran-2-carboxylic acid

Product 1

HCID 68712709(S)-3-methyl-2-{4'-[(3-methyl-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl esterYield 39.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 3-methyl-4-pyridin-3-yl-benzofuran-2-carboxylic acid (123 mg, 0.49 mmol) in 4 mL of DMF was added (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (352 mg, 0.97 mmol), BOP (429 mg, 0.97 mmol), and N,N-diisopropylethylamine (0.17 mL, 0.97 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was poured into brine, and extracted with ethyl acetate. The combined organic solution was washed with brine and water. Removal of solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 115 mg of (S)-3-methyl-2-{4′-[(3-methyl-4-pyridin-3-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester, obtained as white solid.

Workup

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

Sources & evidence

ORD record
ord-a7c128246f874d4abe5e9e1360d0ef19
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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