Lithium Hexamethyldisilazide → HCID 89545333, compound

To a solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (2.8 g, 13 mmol) in tetrahydrofuran (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 15.6 mL, 15.6 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was then cooled to −78° C. and 3,4,5-trifluorobenzene-1-sulfonyl chloride (3.0 g, 13.0 mmol) was added. The mixture was stirred at −78° C. for 0.5 h, warmed to 0° C. and 4,5-trifluorobenzene-1-sulfonyl chloride (0.6 g, 2.6 mmol) was added. The mixture was allowed to warm to ambient temperature, stirred for 20 h, diluted with ethyl acetate (200 mL), washed with saturated aqueous ammonium chloride (200 mL) and brine (200 mL), dried over sodium sulphate, filtered and concentrated in vacuo. The residue was triturated with dichloromethane to afford N-(2,4-dimethoxybenzyl)-3,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a beige solid in 53% yield (3.1 g): 1H NMR (300 MHz, CDCl3) δ8.24-8.18 (m, 1H), 7.37-7.28 (m, 2H), 7.26-7.22 (m, 1H), 7.07 (d, J=8.1 Hz, 1H), 6.39-6.32 (m, 1H), 6.29-6.24 (m, 1H), 5.27 (s, 2H), 3.75 (s, 3H), 3.65 (s, 3H).

1. temperatureThe reaction mixture was then cooled to −78° C.
2. stirringThe mixture was stirred at −78° C. for 0.5 h
3. temperaturewarmed to 0° C.
4. temperatureto warm to ambient temperature
5. stirringstirred for 20 h
6. washwashed with saturated aqueous ammonium chloride (200 mL) and brine (200 mL)
7. dry with materialdried over sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was triturated with dichloromethane

ORD record

ord-2aa748cc0edc450d94a5b411bdd73234

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365578B2