Dichloromethane → HCID 15603652, compound

Participants

Reaction Conditions

Reaction Steps

To a flame-dried round bottom flask was placed 6-chloro-7-(4-chlorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (44 mg, 0.1 mmol), 4-chlorophenylboronic acid (31 mg, 0.2 mmol), K3PO4 (42.5 mg, 0.2 mmol) and [1,1′-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II), complex with CH2Cl2 (1:1) (16 mg, 0.02 mmol). The flask was purged with argon for 15 min before addition of degassed anhydrous THF (1 mL). The reaction mixture was stirred at 70° C. under argon for 16 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc (20 mL), washed with 1 N aqueous NaOH, water, saturated aqueous NaCl, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 60% to 100% B, 8 min gradient, hold at 100% B for 6 min (A=90% H2O, 10% MeOH, 0.1% trifluoroacetic acid and B=10% H2O, 90% MeOH, 0.1% trifluoroacetic acid); Flow rate at 20 mL/min, UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The yellow residue was dissolved in acetonitrile, frozen and lyophilized to afford 18.2 mg (35%) of the title compound as a yellow powder. LC/MS (method A): retention time=3.94 min, (M+H)+=516. 1H NMR (CDCl3, 400 MHz): δ 8.83 (d,J=1.71 Hz, 1H), 7.98 (dd, J=7.95, 2.08 Hz, 1H), 7.69 (d,J=8.07 Hz, 1H), 7.41 (s, 1H), 7.25-7.32 (m, 4H), 7.20-7.23 (m, 2H), 7.00-7.04 (m, 2H), 5.33 (s, 2H).

Provenance & Evidence