反应详情

2-Methylsulfonyl-N-[3-(3-trimethylsilanylethynylphenyl)-1H-indazol-5-yl] benzenesulfonamide can be obtained in the following way: 0.28 g of trimethylsilylacetylene, 0.06 g of copper iodide, 0.03 g of triphenylphosphine, 0.11 g of tetrakis(triphenylphosphine)palladium(0) and 0.29 g of triethylamine are added successively to a solution, under argon, of 0.73 g of N-[3-(3-bromophenyl)-1H-indazol-5-yl]-2-methylsulfonylbenzenesulfonamide in 45 ml of acetonitrile. The reaction mixture is refluxed for 16 hours. After cooling to a temperature in the region of 20° C., 100 ml of water are added to the reaction mixture, which is allowed to settle out. The aqueous phase is extracted with 100 ml of ethyl acetate. The organic extracts are pooled, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is purified by chromatography on a silica column (particle size 40-63 μm), eluting with pure dichloromethane. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is repurified by HPLC chromatography/MS, on a C18 grafted silica column of the X Terra™ type (particle size 5 μm; length×diameter=100×30 mm), eluting with an acetonitrile/water (65/35 by volume) mixture at a flow rate of 20 ml/min. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in 20 ml of ethyl acetate and recrystallized in the presence of 3S black and magnesium sulfate. The crystals are filtered off through sintered glass, washed, partially dried and then dried. 0.05 g of 2-methylsulfonyl-N-[3-(3-trimethylsilanylethynylphenyl)-1H-indazol-5-yl]-benzenesulfonamide is thus obtained in the form of a white crystalline solid melting at 110° C. (analysis LC/MS Tr: 4.25 minutes; [M+.]=523).

1. temperatureThe reaction mixture is refluxed for 16 hours
2. additionare added to the reaction mixture, which
3. extractionThe aqueous phase is extracted with 100 ml of ethyl acetate
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
7. customThe residue is purified by chromatography on a silica column (particle size 40-63 μm)
8. washeluting with pure dichloromethane
9. additionThe fractions containing the expected product
10. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
11. customThe residue is repurified by HPLC chromatography/MS, on a C18
12. washeluting with an acetonitrile/water (65/35 by volume) mixture at a flow rate of 20 ml/min
13. additionThe fractions containing the expected product
14. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
15. customrecrystallized in the presence of 3S black
16. filtrationThe crystals are filtered off through sintered glass
17. washwashed
18. custompartially dried
19. customdried