Toluene → N-((5-(4-cyano-3-fluorophenyl)pyridin-3-yl)(cyclopropyl)-methyl)ethanesulfonamide

Participants

Reaction Conditions

Reaction Steps

Titanium isopropoxide (0.98 mL, 3.36 mmol) was added to a mixture of 2-fluoro-4-(5-formyl-pyridin-3-yl)-benzonitrile (380 mg, 1.68 mmol) and ethanesulfonamide (183 mg, 1.68 mmol) in toluene (14 mL) at RT. The resulting mixture was heated to reflux for 2 h. After concentration, the residue was dissolved in THF (10 mL) and a solution of c-PrMgBr (0.5 M in THF, 16.8 mL, 8.40 mmol) was added dropwise at −40° C., and the resulting mixture was stirred at −36° C. for 1 h. Saturated NH4Cl solution was added to the reaction mixture. The resulting mixture was diluted with ethyl acetate and brine, and subsequently filtered. The organic layer was separated to concentrate and purified by flash column (10% MeOH/DCM=0-30%) to give the title compound (185 mg, 30%); ESI-MS m/z: 360 [M+1]+, 1HNMR (MeOD, 400 MHz) δ ppm 8.85 (1H, d, J=2.0 Hz), 8.72 (1H, d, J=2.0 Hz), 8.25 (1H, t, J=2.0 Hz), 7.94 (1H, d, J=8.0 Hz), 7.82-7.77 (2H, m), 3.95 (1H, d, J=9.2 Hz), 3.89 (3H, s), 3.07-2.96 (2H, m), 1.34-1.29 (1H, m), 1.31 (1H, t, J=7.2 Hz), 0.81-0.76 (1H, m), 0.67-0.62 (2H, m), 0.55-0.51 (1H, m)

Provenance & Evidence