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

To a solution of N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 248, 899 mg, 3.58 mmol) in tetrahydrofuran (6.0 mL), cooled to −78° C., was added lithium hexamethyldisilazide (1.0 M in tetrahydrofuran, 4.3 mL) dropwise. The reaction was stirred for 35 minutes at room temperature, cooled to −78° C. before the dropwise addition of 5-chloro-2,4-difluorobenzenesulfonyl chloride (850 mg, 0.0034 mol). The reaction mixture was stirred at −78° C. for 1 hour then at room temperature for 4 hours. The reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by automated flash chromatography eluting with ethyl acetate:hexanes (gradient 0:1 to 1:0, by volume) to afford the title compound as a white solid, 1.16 g, 73% yield.

1. stirringThe reaction mixture was stirred at −78° C. for 1 hour
2. waitat room temperature for 4 hours
3. extractionextracted with dichloromethane
4. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by automated flash chromatography
9. washeluting with ethyl acetate

ORD record

ord-534ba01eddc44866a91a7178d7c470f1

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541588B2