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

HRID 29438Notes

Reaction equation

HRID 29438 reaction equation
[Na+].[CH3:2][C:3]1[C:8]2[N:9]=[C:10]([C:12]([O-:14])=O)[O:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.[C:15]([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])([CH3:18])([CH3:17])[CH3:16].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>[C:15]([O:19][C:20](=[O:42])[C@@H:21]([NH:25][S:26]([C:29]1[CH:30]=[CH:31][C:32]([C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:12]([C:10]3[O:11][C:7]4[CH:6]=[CH:5][CH:4]=[C:3]([CH3:2])[C:8]=4[N:9]=3)=[O:14])=[CH:39][CH:40]=2)=[CH:33][CH:34]=1)(=[O:28])=[O:27])[CH:22]([CH3:24])[CH3:23])([CH3:17])([CH3:18])[CH3:16]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10525284(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl esterHCID 68714301HCID 68714301, compound

Product 1

HCID 68712161(S)-3-methyl-2-{4'-[(4-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl esterYield 30.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 4-methyl-benzooxazole-2-carboxylic acid sodium salt (180 mg, 0.93 mmol) was added (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester (450 mg, 1.2 eq), BOP (490 mg, 1.2 eq), N,N-diisopropylethylamine (144 mg, 1.2 eq) 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 158 mg of (S)-3-methyl-2-{4′-[(4-methyl-benzooxazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl ester as a 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-a912413578dc4c1db5e146e85f88e8f1
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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