Ammonium Chloride → 3-cyano-N-(2,4-dimethoxybenzyl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

(2,4-Dimethoxy-benzyl)-(1,2,4)thiadiazol-5-yl-amine (Preparation 14, 8.010 g, 0.03200 mol) was dissolved in tetrahydrofuran (100 mL, 1.3 mol) and cooled to −78° C. 1.0 M of Lithium hexamethyldisilazide in tetrahydrofuran (35.2 mL) was added dropwise to the reaction mixture. The cooling bath was removed and the reaction was allowed to stir for 30 minutes. The reaction was cooled back to −78° C. and a solution of 3-cyano-4-fluorobenzenesulfonyl chloride (7.028 g, 0.03200 mol) in tetrahydrofuran (80 mL, 0.99 mol) was added dropwise to the reaction. The reaction was allowed to stir for 30 minutes at −78° C. The reaction was poured into saturated aqueous ammonium chloride. The aqueous phase was extracted with ethyl acetate (three times). The combined organic phase was washed twice with 10% citric acid solution, water and brine. The organic phase was dried over magnesium sulfate and evaporated to a residue. The residue was purified by column chromatography (120 g silica gel column, Hexanes to ethyl acetate gradient elution). Product fractions were combined and evaporated to a residue. The residue was triturated with 10% t-butyl methyl ether in hexanes and the resulting off-white solid collected by filtration and rinsed with hexanes. Vacuum drying gave 3.58 g of the title compound. LCMS Rt=1.66 minutes MS m/z 457 [M Na]+. MS m/z 151 [MH]+2,4-Dimethoxybenzyl 1H NMR (d6-DMSO) δ 8.44 (s, 1H) 8.33 (dd, 1H), 8.25 (m, 1H), 7.72 (t, 1H), 7.03 (d, 1H), 6.43 (m, 2H), 5.23 (s, 2H), 3.73 (s, 3H), 3.64 (s, 3H).

Provenance & Evidence