Diisopropylethylamine → (1R,2R)-2-{4'-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acid

HRID 1691912Notes

Reaction equation

HRID 1691912 reaction equation
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[NH2:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][C:53]([C:56]([C@@H:58]3[CH2:62][CH2:61][CH2:60][C@H:59]3[C:63]([OH:65])=[O:64])=[O:57])=[CH:52][CH:51]=2)=[CH:46][CH:45]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([NH:43][C:44]3[CH:45]=[CH:46][C:47]([C:50]4[CH:55]=[CH:54][C:53]([C:56]([C@@H:58]5[CH2:62][CH2:61][CH2:60][C@H:59]5[C:63]([OH:65])=[O:64])=[O:57])=[CH:52][CH:51]=4)=[CH:48][CH:49]=3)=[O:14])[N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 57652037trans-2-(4'-Amino-biphenyl-4-carbonyl)-cyclopentanecarboxylic acid

Product 1

HCID 57651904(1R,2R)-2-{4'-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acidYield 10.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (0.25 g, 1 mmol) and bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (0.47 g, 1 mmol) in methylene chloride was added racemic trans-2-(4′-amino-biphenyl-4-carbonyl)-cyclopentanecarboxylic acid (0.20 g, 0.78 mmol) and diisopropylethylamine (0.35 mL, 2 mmol). The mixture was stirred at ambient temperature for 3 h. The reaction mixture was concentrated and the residue was re-dissolved in DMSO and acetonitrile. HPLC reverse phase purification with acetonitrile and water afforded 44 mg of racemic trans-2-{4′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acid as a white solid. LCMS calcd for C30H23F3N2O5 (m/e) 548, obsd 549 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was re-dissolved in DMSO
  3. customHPLC reverse phase purification with acetonitrile and water

Sources & evidence

ORD record
ord-3ac8adb3a1b6498997d15ac8f6f7c7b0
Source dataset
uspto-grants-2012_04
Patent number
US08153644B2

Reaction notes

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