Hydrochloric Acid → HCID 58456384, compound

Participants

Reaction Steps

To 2-(5-{3-[(4-{[4-(benzyloxy)cyclohexyl]oxy}pyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,1,1-trifluoropropan-2-ol (Example 94B-3, 0.12 g, 0.21 mmol) was added methanol (0.70 mL) and concentrated hydrochloric acid (6.2 μL, 0.21 mmol). The solution was evacuated and then purged with argon 5 times. 10% Palladium on carbon (0.002 g) was added and the solution was evacuated and then purged with argon 3 times. A balloon filled with hydrogen was placed on top of the reaction and the reaction was evacuated and then backfilled with hydrogen 3 times. The reaction was stirred for four hours. The solution was then filtered carefully through celite. The filtrate was concentrated and purified by reverse phase HPLC (10-100% acetonitrile gradient with water over 12 minutes with a 0.05% trifluoroacetic acid buffer) to afford 4-{[2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}cyclohexanol (30 mg, 0.06 mmol, 30%) as a 60:40 mixture of diastereomers. MS ESI: [M+H]+ m/z 494.7. The following NMR data for the major isomer: 1H NMR (500 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.22-8.15 (m, 1H), 8.08 (s, 1H), 7.74 (s, 1H), 7.68-7.60 (m, 2H), 7.11 (s, 1H), 6.31-6.13 (m, 1H), 5.08-4.93 (m, 1H), 4.65-4.53 (m, 1H), 3.54-3.42 (m, 1H), 2.33 (s, 3H), 2.09-1.98 (m, 1H), 1.91-1.72 (m, 5H), 1.59-1.37 (m, 2H), 1.32-1.19 (m, 2H), 1.12-1.03 (m, 1H). rhSYK activity=+++

Provenance & Evidence