Trifluoroacetic acid → HCID 67241339, compound

Participants

Reaction Conditions

Reaction Steps

A sealed tube was charged with a stir bar, 4-[5-(3-amino-5-methylphenyl)-4-chloro-1,3-thiazol-2-yl]-1,4-diazepan-2-one (45 mg, 0.134 mmol), 2-chloro-4-methoxypyrimidine, (20 mg, 0.138 mmol), potassium carbonate (37 mg, 0.268 mmol), Pd2(dba)3 (13 mg, 0.013 mmol), and dicyclohexyl[2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (X-Phos, 31.8 mg, 0.067 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed t-amyl alcohol (450 μl) was added, the tube was sealed and heated at 80° C. for 16 h with stirring. The reaction mixture was then cooled and filtered through a celite plug, which was rinsed with 10% isopropanol in CHCl3. The eluent was concentrated and purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water (30-100%), providing 4-(4-chloro-5-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one (19 mg, 0.032 mmol, 29.1%) as a TFA salt. APCI: [M+H]+ m/z 440.1. 1H NMR (500 MHz, dmso) δ9.65 (s, 1H), 8.19 (d, J=5.7, 1H), 7.90 (s, 1H), 7.66 (s, 1H), 7.50 (s, 1H), 6.98 (s, 1H), 6.29 (d, J=5.7 Hz, 1H), 4.15 (s, 2H), 3.93 (s, 3H), 3.76 (s, 2H), 3.23 (s, 2H), 2.28 (s, 3H), 1.77 (s, 2H). rhSYK activity=+++.

Provenance & Evidence