Reaktion #53741

Reaktionsgleichung

ethanethiol

boron trifluoride etherate

benzyl 4-(3-phenyl-1H-indazol-5-ylsulfamoyl)piperidine-1-carboxylate

→

N-(3-phenyl-1H-indazol-5-yl)piperidine-4-sulfonamide

Ausbeute 11.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenis then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
2. 2
   Extraktionextracted successively with 30 ml and 15 ml of ethyl acetate
3. 3
   Trocknendried over magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
6. 6
   SonstigeThe residue thus obtained
7. 7
   Sonstigeis purified by chromatography on a silica column (particle size 40-63 μm)
8. 8
   Wascheneluting successively with dichloromethane/methanol (99/1; 95/5 by volume) mixtures
9. 9
   workup.ADDITIONThe fractions containing the expected product
10. 10
    Einengenconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
11. 11
    workup.DISSOLUTIONdissolved under hot conditions
12. 12
    Filtrationthe mixture is filtered under hot conditions through sintered glass
13. 13
    Sonstigerecrystallized
14. 14
    FiltrationThe crystals are filtered off through sintered glass
15. 15
    Waschenwashed with 2 times 0.5 ml
16. 16
    Trocknen1 ml of acetonitrile, partially dried
17. 17
    Sonstigedried under reduced pressure (3 kPa) at a temperature in the region of 50° C

Vorschrift

N-(3-Phenyl-1H-indazol-5-yl)piperidine-4-sulfonamide can be obtained in the following way: 1.89 g of ethanethiol, then 1.45 g of boron trifluoride etherate, are added dropwise to a solution, under argon, of 0.5 g of benzyl 4-(3-phenyl-1H-indazol-5-ylsulfamoyl)piperidine-1-carboxylate in 5 ml of dichloromethane. The reaction mixture is stirred at a temperature in the region of 20° C. for 16 hours and is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in 10 ml of water, basified with 5 ml of an aqueous 32% ammonium hydroxide solution, and then extracted successively with 30 ml and 15 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 thus obtained is purified by chromatography on a silica column (particle size 40-63 μm), eluting successively with dichloromethane/methanol (99/1; 95/5 by volume) mixtures. 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 taken up in 6 ml of acetonitrile in the presence of 3S black, and dissolved under hot conditions, and the mixture is filtered under hot conditions through sintered glass and then recrystallized. The crystals are filtered off through sintered glass, washed with 2 times 0.5 ml then 1 ml of acetonitrile, partially dried and then dried under reduced pressure (3 kPa) at a temperature in the region of 50° C. 0.04 g of N-(3-phenyl-1H-indazol-5-yl)piperidine-4-sulfonamide is thus obtained in the form of a white crystalline solid melting at 230° C. (analysis: C18H20N4O2S, % calculated C, 60.65, H 5.66; N, 15.72; O, 8.98; S, 9. % found C, 60.62; H, 5.85; N, 15.39; S, 8.72).

Quelle