Hydrochloric Acid → HCID 178525700, compound

Participants

Reaction Steps

To a solution of methyl trans-4-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylate (Example 21-11, 91 mg, 0.197 mmol) in tetrahydrofuran (2.00 mL) and methanol (0.75 mL) was added aqueous 1N LiOH (0.590 mL, 0.590 mmol). The resultant solution was stirred 20 minutes at room temperature and then 30 minutes at 50° C. The solution cooled to room temperature and was quenched with HCl (0.571 mL, 0.571 mmol) and then aqueous 25% NH4OAc solution (to pH=7). The mixture was extracted with 2-Me-THF. The combined organic fractions were washed with brine, dried (Na2SO4), and were filtered before concentration to dryness. The residue was triturated in hot ethyl acetate. The product was collected by filtration (wash with ethyl acetate, then ether and then hexanes) to yield trans-4-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (37.6 mg 0.084 mmol, 43%) as a yellowish solid. MS APCI [M+H]+ m/z 449.1. 1H NMR (400 MHz, DMSO) δ 12.12 (s, 1H), 10.34 (s, 1H), 8.86 (d, J=4.9, 1H), 8.15 (s, 1H), 7.99 (s, 1H), 7.66 (d, J=8.0, 1H), 7.39 (t, J=7.9, 1H), 7.35-7.29 (m, 2H), 3.07-2.89 (m, 1H), 2.30 (ddd, J=11.5, 6.8, 2.5, 1H), 2.16 (d, J=10.4, 2H), 2.09-1.96 (m, 2H), 1.66-1.41 (m, 4H). rhSYK Activity: +++

Provenance & Evidence