Lithium hexamethyldisilazane → 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide

Temperatur

0 °C

A solution of (2,4-dimethoxybenzyl)-pyrimidin-2-yl-amine (Preparation 12, 736 mg, 3 mmol) in anhydrous tetrahydrofuran (20 mL) was cooled to −78° C. before the addition of a 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (3.30 mL, 3.30 mmol). The reaction was allowed to warm to 0° C. for 30 minutes before cooling again to −78° C. The resulting solution was added to a solution of 3-chloro-4,6-difluorobenzenesulfonyl chloride (890 mg, 3.6 mmol) in tetrahydrofuran (10 mL) at −78° C. After 30 minutes at this temperature the reaction was warmed to room temperature and stirred for 24 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and extracted into ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (50-100% dichloromethane in heptane gradient elution) to afford the title compound as a white solid (260 mg, 19%).

1. temperaturebefore cooling again to −78° C
2. temperatureAfter 30 minutes at this temperature the reaction was warmed to room temperature
3. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution
4. extractionextracted into ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel column chromatography (50-100% dichloromethane in heptane gradient elution)

ORD-Eintrag

ord-0fb9cb2580a245ffae0267812946164f

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08772293B2