Reacción #74612

Ecuación de reacción

N,N-diisopropylethylamine

pyridine

5-Chloro-2,4-difluorobenzenesulfonyl chloride

2-amino-5-fluoropyridine

chloromethyl methyl ether

→

title compound

5-Chloro-2,4-difluoro-N-(5-fluoropyridin-2-yl)-N-(methoxymethyl)benzenesulfonamide

Disolventes

dichloromethane

dichloromethane

dichloromethane

hydrochloric acid

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter addition
2. 2
   Temperaturathe reaction mixture was warmed to room temperature
3. 3
   ExtracciónThe aqueous layer was extracted with dichloromethane
4. 4
   LavadoThe combined organic layers were washed with water
5. 5
   workup.ADDITIONdiluted with ethyl acetate
6. 6
   Secadodried over sodium sulfate
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane (8.0 mL)
10. 10
    TemperaturaThe mixture was cooled to 0° C.
11. 11
    TemperaturaThe reaction mixture was warmed to room temperature
12. 12
    Lavadowashed with saturated aqueous sodium bicarbonate solution
13. 13
    SecadoThe organic layer was dried over sodium sulfate
14. 14
    Filtraciónfiltered
15. 15
    Concentraciónconcentrated in vacuo onto Celite™
16. 16
    OtroThe residue was purified by automated flash chromatography (24 g silica gel column)
17. 17
    Lavadoeluting with ethyl acetate

Procedimiento

5-Chloro-2,4-difluorobenzenesulfonyl chloride (1 g, 4 mmol) in dichloromethane (7.6 mL) was added portion-wise to a solution of 2-amino-5-fluoropyridine (498 mg, 4.44 mmol) in pyridine (7.6 mL, 94 mmol) cooled to 0° C. After addition was complete, the reaction mixture was warmed to room temperature. After 16 hours, the reaction mixture was diluted with dichloromethane and hydrochloric acid (1 N aqueous solution). The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with water, diluted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in dichloromethane (8.0 mL) and N,N-diisopropylethylamine (0.776 mL, 4.45 mmol) added. The mixture was cooled to 0° C. and chloromethyl methyl ether (0.338 mL, 4.45 mmol) was added dropwise by syringe. The reaction mixture was warmed to room temperature and after stirring for 6 hours, the reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo onto Celite™. The residue was purified by automated flash chromatography (24 g silica gel column) eluting with ethyl acetate:hexanes (gradient 0:1 to 1:0, by volume) to afford the title compound, 363 mg.

Fuente