Hydrochloric Acid → Cyclohexanecarboxylic acid

Temperature

80 °C

To a solution of methyl trans-4-[(1R or 1S)-1-hydroxy-1-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-2,3′-bipyridin-6′-yl)ethyl]cyclohexanecarboxylate (83 mg, 0.161 mmol) in methanol (1.5 ml) was added sodium hydroxide (1.0 M in water, 560 μl, 0.560 mmol). The mixture was then heated to a temperature of 80° C. for 60 minutes. The reaction was subsequently allowed to cool to room temperature and the pH was lowered to 5-6 by dropwise addition of hydrochloric acid (2N in water). The resulting suspension was filtered to afford trans-4-((1R or 1S)-1-hydroxy-1-(4-methyl-6-(4-(trifluoromethyl)pyridin-2-ylamino)-2,3′-bipyridin-6′-yl)ethyl)cyclohexanecarboxylic acid (52 mg, 0.104 mmol, 64.4% yield) as a colorless solid. MS ESI calcd. for C26H28F3N4O3 [M+H]+ 501. found 501. 1H NMR (500 MHz, DMSO-d6) δ 11.94 (br s, 1H), 10.21 (s, 1H), 9.12 (s, 1H), 8.58 (s, 1H), 8.49 (d, J=5.1 Hz, 1H), 8.33 (d, J=8.3 Hz, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.45 (s, 1H), 7.29 (s, 1H), 7.20 (d, J=5.1 Hz, 1H), 5.05 (s, 1H), 2.35 (s, 3H), 2.05-1.66 (m, 5H), 1.43 (s, 3H), 1.15-1.0 (m, 5H). rhSyk IC50=<0.5 nM

1. temperatureto cool to room temperature
2. filtrationThe resulting suspension was filtered
3. customto afford trans-4-((1R

ORD record

ord-1c6ee96f70f6436cbb44871e1a4d31d7

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145391B2