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

HRID 29376Notes

Reaction equation

HRID 29376 reaction equation
[CH3:1][C:2]1[C:6]2[C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]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>[Cl-].[Na+].O.CN(C=O)C>[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]([N:11]5[CH2:12][CH2:13][O:14][CH2:15][CH2:16]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 687173063-Methyl-4-morpholin-4-yl-benzofuran-2-carboxylic acid

Product 1

HCID 68712374(S)-3-methyl-2-{4'-[(3-methyl-4-morpholin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl esterYield 82.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 3-methyl-4-morpholin-4-yl-benzofuran-2-carboxylic acid (97 mg, 0.37 mmol) was added (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester (268 mg, 0.74 mmol), BOP (327 mg, 0.74 mmol), N,N-diisopropylethylamine (0.13 mL, 0.74 mmol) and 4 mL of DMF. 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 the solvent in vacuo gave the crude product, which was purified by column chromatography on silica gel to give 184 mg of (S)-3-methyl-2-{4′-[(3-methyl-4-morpholin-4-yl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid methyl ester, obtained as an off-white solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic solution was 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-254c3f37e6174c86adc24aab4142f2a6
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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