Potassium Carbonate → N-(5-Chloro-1,3-thiazol-2-yl)-4-(4-cyano-2-iodophenoxy)-2,5-difluorobenzenesulfonamide

Temperatur

65 °C

To a suspension of potassium carbonate (0.068 g, 0.000492 mol) and N-(5-chloro-1,3-thiazol-2-yl)-N-(2,4-dimethoxybenzyl)-2,4,5-trifluorobenzenesulfonamide (Preparation 334, 0.200 g, 0.000418 mol) in dimethyl sulfoxide (3.0 mL) was added 4-hydroxy-3-iodobenzonitrile (Preparation 342, 0.108 g, 0.000441 mol) and was stirred at 65° C. under nitrogen for 16 hours. The reaction was diluted with ethyl acetate (10.0 mL). The organic phase was washed with saturated aqueous sodium chloride solution (2×10.0 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude was dissolved in dichloromethane (1.5 mL), treated with trifluoroacetic acid (1.5 mL) and stirred at room temperature under nitrogen for 16 hours. Reaction was concentrated in vacuo and residue dissolved in ethyl acetate (10.0 mL). The organic extract was washed with saturated aqueous sodium bicarbonate solution (2×10.0 mL), dried over sodium sulphate, filtered and concentrated in vacuo. The resulting residue was purified using ISCO™ (12 g SiO2) eluting with methanol:dichloromethane (gradient 0:1 to 1:39, by volume) to afford the title compound as an orange solid, 165 mg, 35% yield.

1. washThe organic phase was washed with saturated aqueous sodium chloride solution (2×10.0 mL)
2. dry with materialdried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. dissolutionThe crude was dissolved in dichloromethane (1.5 mL)
6. additiontreated with trifluoroacetic acid (1.5 mL)
7. stirringstirred at room temperature under nitrogen for 16 hours
8. customReaction
9. concentrationwas concentrated in vacuo and residue
10. dissolutiondissolved in ethyl acetate (10.0 mL)
11. extractionThe organic extract
12. washwas washed with saturated aqueous sodium bicarbonate solution (2×10.0 mL)
13. dry with materialdried over sodium sulphate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customThe resulting residue was purified
17. washeluting with methanol

ORD-Eintrag

ord-8ea28955b0174c21bd65d3e9e64f2209

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08541588B2