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

HRID 29421Notes

Reaction equation

HRID 29421 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([OH:13])=O)=[C:8]([CH3:14])[C:7]=2[C:15]=1[O:16][CH3:17])#[N: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>[Cl-].[Na+].O.CN(C=O)C>[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:11]([C:9]3[O:10][C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[C:15]([O:16][CH3:17])[C:7]=4[C:8]=3[CH3:14])=[O:13])=[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 68716451HCID 68716451, compound

Product 1

HCID 68711753(S)-2-{4'-[(5-cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl esterYield 32.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 110 mg (0.48 mmol) of 5-cyano-4-methoxy-3-methyl-benzofuran-2-carboxylic acid was added 207 mg (1.2 eq) of (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester, BOP (252 mg, 1.2 eq), N,N-diisopropylethylamine (74 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 crude product, which was purified by column chromatography on silica gel to give 89 mg (32% yield) of (S)-2-{4′-[(5-cyano-4-methoxy-3-methyl-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-3-methyl-butyric acid methyl 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. customConcentration of the organics in vacuo gave crude product, which
  4. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c54b20cf3d2e4e309f11fefb1ed5709b
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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