Dichloromethane → 2-Chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid

Participants

Reaction Steps

A suspension of 6-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (2290 mg, 6903 μmol), 4-bromo-2-chlorobenzoic acid (2766 mg, 13805 μmol), Na2CO3 (2 M, 13805 μl, 27611 μmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) complex with dichloromethane (505 mg, 690 μmol) in DME (20 mL) was sparged with argon for 10 minutes then heated to reflux for 7 hours. The reaction was then partitioned between NaOH (1 M, 75 mL) and EtOAc (25 mL). The organic layer was discarded and the aqueous layer acidified to pH 4 with HCl (2M). The resulting orange precipitate was then collected by filtration and washed with water (50 mL). MS (ESI pos. ion) m/z: 452 (MH+); calc'd for C23H18ClN3O5: 451. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.86 (s, 3 H) 4.68 (s, 4 H) 6.94 (d, J=4.52 Hz, 1 H) 7.02 (d, J=9.03 Hz, 1 H) 7.09 (d, J=9.54 Hz, 1 H) 7.27 (s, 1 H) 7.60 (d, J=7.03 Hz, 1 H) 7.75 (d, J=7.03 Hz, 1 H) 7.81-7.98 (m, 2 H) 8.09 (d, J=9.54 Hz, 1 H) 8.62 (d, J=4.02 Hz, 1 H).

Provenance & Evidence