反应详情

To a suspension of N′-(6-(2-chlorophenyl)-5-(4-chlorophenyl)pyridazin-3-yl)-2-cyclohexylacetohydrazide (46 mg, 0.1 mmol) in THF (2 mL) at room temperature was added diisopropylethylamine (0.14 mL, 0.8 mmol). After 5 min, triphenylphosphine dichloride (110 mg, 0.33 mmol) was added, and the reaction mixture stirred at room temperature for 16 h. Analysis by HPLC/MS indicated the reaction was complete. The reaction was diluted with EtOAc (40 mL), washed with H2O, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated. The obtained residue was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-30%) in hexanes to yield 45 mg of the desired product with 80% purity (contaminated with triphenylphosphine oxide). The product was further purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5 μC18 21.2×100 mm; Eluted with 70% to 100% B, 8 min gradient, 100% B hold for 7 min, (A=90% H2O, 10% MeOH and B=10% H2O, 90% MeOH); Flow rate at 20 mL/min, UV detection at 220 nm) to afford 30 mg (68%) of the title compound as a white powder. HPLC/MS (method A): retention time=4.22 min, (M+H)+=437.1. 1H NMR (CDCl3, 400 MHz): δ 8.03 (s, 1H), 7.33-7.41 (m, 4H), 7.21-7.28 (m, 2H), 7.07 (d, J=8.31Hz, 2H), 3.14 (d, J=7.09 Hz, 2H), 2.01-2.12 (m, 1H), 1.69-1.80 (m, 4H), 1.21-1.29 (m, 3H), 1.10-1.17 (m, 3H).

1. washwashed with H2O, saturated aqueous NaCl
2. dry with materialdried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated
5. customThe obtained residue was purified
6. washeluting with a gradient of EtOAc (0-30%) in hexanes