Hydrochloric Acid → 2-({4'-[(5-Fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

HRID 9604Notes

Reaction equation

HRID 9604 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([C@@H:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[C:21]([O:23]C)=[O:22])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:27]=[CH:28][C:29]2[O:33][C:32](S(C)(=O)=O)=[N:31][C:30]=2[CH:38]=1.[OH-].[Na+].Cl>ClC(Cl)C.CO>[F:25][C:26]1[CH:27]=[CH:28][C:29]2[O:33][C:32]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([CH:16]5[CH2:20][CH2:19][CH2:18][CH:17]5[C:21]([OH:23])=[O:22])=[O:15])=[CH:10][CH:9]=4)=[CH:6][CH:7]=3)=[N:31][C:30]=2[CH:38]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11416053Cyclopentanecarboxylic acid, 2-[(4'-amino[1,1'-biphenyl]-4-yl)carbonyl]-, methyl ester, (1R,2R)-HCID 219857385-Fluoro-2-(methylsulfonyl)-1,3-benzoxazole

Product 1

HCID 219857182-({4'-[(5-Fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acidYield 31.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclopentane carboxylate (100 mg, 0.31 mmol) in dichloroethane (3 mL), 5-fluoro-2-(methylsulfonyl)-1,3-benzoxazole (80 mg, 0.37 mmol) was added and the mixture was heated at 85° C. overnight. The solvent was removed by rotary evaporation, and the residue was redissolved in DMF (5 mL). A solution of 1 N aqueous NaOH (0.93 mL, 0.93 mmol) was added and the mixture was heated at 65° C. overnight. A solution of 1 N aqueous HCl (0.31 mL, 0.31 mmol) and methanol (5 mL) were added to the reaction mixture, and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 2-({4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid as a white solid (43.7 mg, 31.4%). 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, 2 H), 7.90–7.80 (m, 6 H), 7.50 (m, 1 H), 7.30 (m, 1 H), 6.95 (m, 1 H), 4.05 (m, 1 H), 3.20 (m, 1 H), 2.20 (m, 1 H), 1.95 (m, 1 H), 1.80–1.60 (m, 4 H); LC-MS ret. time 3.66 min (method 2), m/z 445.1 (MH+).

Workup

  1. customThe solvent was removed by rotary evaporation
  2. dissolutionthe residue was redissolved in DMF (5 mL)
  3. temperaturethe mixture was heated at 65° C. overnight
  4. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Sources & evidence

ORD record
ord-413351cac0774ed5921977575cb1bfa8
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

Loading…