Hydrochloric Acid → trans-2-({4'-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

Temperature

90 °C

Methyl 2-[(4′-aminobiphenyl-4-yl)carbonyl]cyclopentanecarboxylate (264 mg, 0.02 mmol) was dissolved in n-butanol (8 mL), 2-chloro-5,6-difluoro-1H-benzimidazole (185 mg, 0.98 mmol) and 4 N HCl (0.2 mL) were then added, and the resulting mixture was heated at 90° C. for 5 h. The mixture was then cooled to rt, and solvent was removed under reduced pressure. The residue was dissolved in methanol (5 mL) and tetrahydrofuran (5 mL), and then treated with I N aqueous sodium hydroxide (2.45 mL, 2.45 mmol). The mixture was stirred at rt for 16 h and then concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford trans-2-({4′-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid (9.1 mg, 3%). LC-MS m/z 462.3 (MH+), ret. time 3.23 min; 1H NMR (300 MHz, DMSO-d6) δ 1.69-1.81 (m, 4H), 1.98-2.18 (m, 2H), 3.14-3.22 (m, 1H), 4.04-4.09 (m, 1H), 7.38 (t, 2H), 7.77-7.84 (m, 6H), 8.05 (d, 2H).

1. temperatureThe mixture was then cooled to rt
2. customsolvent was removed under reduced pressure
3. dissolutionThe residue was dissolved in methanol (5 mL)
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

ORD record

ord-86105a0989804e78978f541f97d08ba8

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07423156B2