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

HRID 29446Notes

Reaction equation

HRID 29446 reaction equation
[Na+].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([C:11]([O-:13])=O)=[N:8][C:7]=2[CH:14]=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:11]([C:9]3[S:10][C:6]4[CH:5]=[CH:4][C:3]([Cl:2])=[CH:14][C:7]=4[N:8]=3)=[O:13])=[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 68717138Sodium 5-chloro-1,3-benzothiazole-2-carboxylate

Product 1

HCID 68713740(S)-3-methyl-2-{4'-[(5-chloro-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl esterYield 35.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 5-chloro-benzothiazole-2-carboxylic acid sodium salt (150 mg, 0.64 mmol) was added (S)-2-(4′-amino-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester (310 mg, 1.2 eq), BOP (340 mg, 1.2 eq), N,N-diisopropylethylamine (99 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 solvent gave the crude product, which was purified by column chromatography on silica gel to give 136 mg of (S)-3-methyl-2-{4′-[(5-chloro-benzothiazole-2-carbonyl)-amino]-biphenyl-4-sulfonylamino}-butyric acid tert-butyl ester was obtained as a white solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic solution was 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-cd4feb128f7b468599deeef2401aa2c1
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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