Hydrochloric Acid → HCID 178504714, compound

HRID 25448Notes

Reaction equation

HRID 25448 reaction equation
Cl.[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[S:12]([NH:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[N:21](COCC[Si](C)(C)C)[N:20]=[C:19]2[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:14])=[O:13])(=[O:5])=[O:4].[OH-].[Na+]>C(O)C.C(OC(C)C)(C)C>[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[S:12]([NH:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][N:20]=[C:19]2[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:14])=[O:13])(=[O:5])=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22567026HCID 22567026, compound

Product 1

HCID 178504714HCID 178504714, compoundYield 29.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 7914Diisopropyl EtherSolvent

Conditions

Temperature
20 °C

Procedure

2-Methylsulfonyl-N-(3-phenethyl-1H-indazol-5-yl)benzenesulfonamide can be obtained in the following way: 5.6 ml of an aqueous 5N hydrochloric acid solution are added dropwise to a suspension of 0.56 g of 2-methylsulfonyl-N-[3-phenethyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazol-5-yl]benzenesulfonamide in 17 ml of absolute ethanol. The reaction mixture is then refluxed for 30 minutes and then cooled to a temperature in the region of 20° C. 6.8 ml of an aqueous 5N sodium hydroxide solution are then added and the mixture is stirred. The mixture is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. and the residue is taken up in a mixture of 35 ml of ethyl acetate and of 50 ml of water. After settling out, the aqueous phase is extracted with 2 times 30 ml of ethyl acetate. The organic extracts are pooled, washed with 2 times 20 ml of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C. The residue thus obtained is purified by chromatography under argon pressure (50 kPa) on a column of 75 g of silica (particle size 40-63 μm), eluting with a dichloromethane/methanol (98/2 by volume) mixture. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C. The residue thus obtained is repurified by chromatography under argon pressure (50 kPa), on a column of silica (particle size 40-63 μm), eluting with a cyclohexane/ethyl acetate (70/30 by volume) mixture. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C. The residue thus obtained is taken up in 15 ml of diisopropyl ether, triturated, filtered and then dried. 130 mg of 2-methylsulfonyl-N-(3-phenethyl-1H-indazol-5-yl)benzenesulfonamide are thus obtained in the form of a white solid melting at 192° C. (CI mass analysis: m/z 456 (M+H)+).

Workup

  1. temperatureThe reaction mixture is then refluxed for 30 minutes
  2. concentrationThe mixture is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C.
  3. additionthe residue is taken up in a mixture of 35 ml of ethyl acetate and of 50 ml of water
  4. extractionthe aqueous phase is extracted with 2 times 30 ml of ethyl acetate
  5. washwashed with 2 times 20 ml of a saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  9. customThe residue thus obtained
  10. customis purified by chromatography under argon pressure (50 kPa) on a column of 75 g of silica (particle size 40-63 μm)
  11. washeluting with a dichloromethane/methanol (98/2 by volume) mixture
  12. additionThe fractions containing the expected product
  13. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  14. customThe residue thus obtained
  15. customis repurified by chromatography under argon pressure (50 kPa)
  16. washon a column of silica (particle size 40-63 μm), eluting with a cyclohexane/ethyl acetate (70/30 by volume) mixture
  17. additionThe fractions containing the expected product
  18. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  19. customThe residue thus obtained
  20. customtriturated
  21. filtrationfiltered
  22. customdried

Sources & evidence

ORD record
ord-04bdd681d2ab45e0976a8096edd5a73f
Source dataset
uspto-grants-2005_02
Patent number
US06858638B2

Reaction notes

Loading…