HCID 67431287, compound → HCID 67260166, compound

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyl 4-hydroxy-4-{5-[3-({4-[(1E)-3-methoxyprop-1-en-1-yl]pyrimidin-2-yl}amino)-5-methylphenyl]-1,3-thiazol-2-yl}cyclohexanecarboxylate (100 mg, 0.19 mmol, 1.0 equiv) was dissolved in absolute EtOH (10 ml), deoxygenated, and treated with 10% Pd on carbon (50 mg, 0.47 mmol, 2.5 equiv). The mixture was deoxygenated further before being placed under hydrogen balloon and stirred for at 23° C. for 1 h. The reaction was 50% complete so it was maintained under H2 at 23° C. for another 1 h. The black mixture was filtered through a pad of Celite, which was then washed with EtOAc, dichloromethane, and MeOH. The filtrate was concentrated in vacuo, then purified by reverse-phase HPLC (acetonitrile/water gradient with 0.05% TFA present). The TFA salt was converted to the free base by partitioning between EtOAc (60 ml) and saturated aqueous NaHCO3 (70 ml). The organic layers were dried over MgSO4, filtered and concentrated to afford the title compound (29.1 mg, 27.5%) as a yellow-orange oil. MS ESI: [M+H]+ m/z 539.1. 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J=3.4 Hz, 1H), 7.90 (m, 1H), 7.84 (s, 1H), 7.32 (s, 1H), 7.00 (s, 1H), 6.61 (m, 1H), 3.46-3.45 (m, 5H), 2.74-2.72 (m, 2H), 2.36 (s, 3H), 2.30 (m, 1H), 2.15-2.00 (m, 6H), 1.92-1.85 (m, 4H), 1.45 (s, 9H). rhSYK activity=++

Provenance & Evidence