Water → HCID 71208632, compound

Participants

Reaction Conditions

Reaction Steps

While purging with argon, a small microwave tube was charged with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (30.0 mg, 0.155 mmol), K3PO4.H2O (53 mg, 0.230 mmol), and PdCl2(dppf) (9.3 mg, 0.013 mmol). 6-Bromo-N-[7-chloro-1-(2-chloro-phenyl)-4-oxo-1,4-dihydro-quinolin-3-yl-methyl]-nicotinamide (Example I-101) (50 mg, 0.099 mmol) in DMF (0.50 mL) was added followed by water (0.05 mL). The reaction mixture was heated at 120° C. via microwave irradiation for 15 min. HPLC showed one or two new peaks forming; LC/MS showed one of the new peaks with the product mass. The reaction mixture was heated at 120° C. for another 40 min. After this time, most of the starting material was consumed, as observed by HPLC. The reaction mixture was diluted with H2O, then extracted twice with ethyl acetate. The combined ethyl acetate layers were washed with brine. The organic phase was dried over Na2CO3, filtered, and concentrated. The crude product was purified using flash chromatography (12 g silica gel column eluting with 100% methylene chloride ramped to 0% methanol in methylene chloride). N-[7-Chloro-1-(2-chloro-phenyl)-4-oxo-1,4-dihydro-quinolin-3-ylmethyl]-6-(1H-pyrazol-4-yl)-nicotin-amide (3.7 mg, 7%) was obtained as a light brown solid at 90% purity by reverse-phase HPLC. MS calcd. for C25H17Cl2N5O2 [(M+H)+] 491.0, obsd. 489.9.

Provenance & Evidence