Hydrochloric Acid → HCID 178428305, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of butyl trans-4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate (600 mg, 1.066 mmol) in methanol (10.7 mL) was added sodium hydroxide (1.0 M in H2O, 2.13 mL, 2.13 mmol) and the reaction was heated overnight at 100° C. The reaction was then cooled to room temperature, acidified with HCl (1.0 M in H2O) to a pH of ˜3 and then diluted with water and ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated. The residue was purified and at the same time the enantiomers separated by supercritical fluid chromatography (Chiral OJ column, 35%:75% methanol/CO2 5.0 min run time) to yield trans-4-{(1R)-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylic acid and trans-4-{(1S)-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylic acid. Characterization data for the faster eluting enantiomer (Rt=3.22 min): MS ESI calc'd. for C24H26F3N4O3S [M+H]+ 507. found 507. 1H NMR (500 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.83 (d, J=4.9, 1H), 7.99-7.92 (m, 2H), 7.45 (s, 1H), 7.27 (d, J=4.9, 1H), 7.14 (s, 1H), 5.82 (s, 1H), 2.31 (s, 3H), 2.10-1.95 (m, 1H), 1.95-1.73 (m, 2H), 1.72-1.58 (m, 1H), 1.58-1.50 (m, 1H), 1.47 (s, 3H), 1.32-1.11 (m, 4H), 1.10-0.94 (m, 1H). rhSyk=+++. The slower eluting enantiomer Rt=4.04 min. rhSyk=+++

Provenance & Evidence