Tri-o-tolylphosphine → 4-Chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide

Participants

Reaction Conditions

Reaction Steps

tri-o-Tolylphosphine (2.0E1 mg, 0.064 mmol) was stirred in DMF (2 mL). The mixture was degassed by bubbling nitrogen through it until all additions were complete. To the mixture was added palladium acetate (7.2 mg, 0.032 mmol), and the resulting mixture was stirred at 20° C. for 5 min. To the resulting mixture was added sodium acetate (39.5 mg, 0.482 mmol) and 6-chloro-3′-[(5-iodopyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]biphenyl-3-carboxamide (0.191 g, 0.321 mmol). The resulting mixture was heated to reflux. After 4 h, LCMS showed complete reaction to give the desired product, M+H 467; and small amounts of reduction product (M+H 469) and de-chlorination product (M+H 433). The product was isolated by prep HPLC using a 30 mm×100 mm C18 column; 35% CH3CN—H2O (0.1% TFA), 1.5 min, to 55% at 6 min; 60 mL/min; detector set at 285 nm; retention time, 4.9 min; retention time of the de-chlorination product, 4.5 min. The HPLC fractions were freeze-dried to yield product TFA salt, a white solid; 1H NMR (DMSO-d6) δ 13.0 (s, 1H, NH); 10.7 (s, 1H, amide NH); 9.63 (s, 1H, NH); 9.11 (s, 1H); 8.44 (d, 1H); 8.36 (s, 1H); 8.27 (s, 1H); 8.09 (d, 1H); 8.02 (t, 2H); 7.95 (s, 1H); 7.84 (d, 1H); 7.70 (t, 1H); 7.62 (t, 1H); 7.47 (d, 1H).

Provenance & Evidence