Cesium carbonate → N-(1-chloro-9-fluorobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 1,6-dichloro-9-fluorobenzo[c]-1,6-naphthyridine (30 mg, 0.11 mmol) in dioxane (3 mL) were added cesium carbonate (128 mg, 0.39 mmol), piperidine-1-sulfonamide (18.4 mg, 0.11 mmol), Xantphos, (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine), (10 mg, 0.02 mmol), and Pd2(dba)3 (5.14 mg, 5.62 μmol). The solution was degassed by bubbling N2 for 5 min and heated 80° C. overnight and worked up with EtOAc and H2O. The organic layers were dried with MgSO4, filtered, and concentrated by rotary evaporation to afford an oily residue. Silica gel column chromatography 100% CH2Cl2 to 25% MeOH afforded N-(1-chloro-9-fluorobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide. This intermediate was taken up in 6 N HCl (2 mL) and THF (2 mL) and heated to 85° C. for 2 hr. The reaction mixture was concentrated and purified by reverse phase HPLC 100% H2O to 100% MeCN to afford N-(9-fluoro-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide. LRMS (ESI) calc'd for (C17H18FN4O3S) [M+H]+, 377.1; found 377.1.

Provenance & Evidence