Dimethylformamide → (S)-3-methyl-2-{4'-[(5-trifluoromethyl-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl ester

HRID 29450Notes

Reaction equation

HRID 29450 reaction equation
[Na+].[F:2][C:3]([F:17])([F:16])[C:4]1[CH:5]=[CH:6][C:7]2[S:11][C:10]([C:12]([O-:14])=O)=[N:9][C:8]=2[CH:15]=1.[C:18]([O:22][C:23](=[O:45])[C@@H:24]([NH:28][S:29]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)=[CH:34][CH:33]=1)(=[O:31])=[O:30])[CH:25]([CH3:27])[CH3:26])([CH3:21])([CH3:20])[CH3:19].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN(C=O)C>[Cl-].[Na+].O>[C:18]([O:22][C:23](=[O:45])[C@@H:24]([NH:28][S:29]([C:32]1[CH:33]=[CH:34][C:35]([C:38]2[CH:39]=[CH:40][C:41]([NH:44][C:12]([C:10]3[S:11][C:7]4[CH:6]=[CH:5][C:4]([C:3]([F:2])([F:17])[F:16])=[CH:15][C:8]=4[N:9]=3)=[O:14])=[CH:42][CH:43]=2)=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH:25]([CH3:27])[CH3:26])([CH3:20])([CH3:21])[CH3:19]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10525284(S)-2-(4'-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl esterHCID 687139225-Trifluoromethyl-benzothiazole-2-carboxylic acid sodium salt

Product 1

HCID 68714729(S)-3-methyl-2-{4'-[(5-trifluoromethyl-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl esterYield 37.4%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To 5-trifluoromethyl-benzothiazole-2-carboxylic acid sodium salt (260 mg, 0.97 mmol) was added (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester (469 mg, 1.2 eq), BOP (515 mg, 1.2 eq) and 5 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 layers were washed with brine and water. Removal of solvent gave the crude product, which was purified by column chromatography on silica gel to give 230 mg of (S)-3-methyl-2-{4′-[(5-trifluoromethyl-benzothiazole-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 layers were washed with brine and water
  3. customRemoval of solvent
  4. customgave the crude product, which
  5. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-a8de0e0a6e7a45f6aadfad65a8312bc2
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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