2-Methanesulfonylbenzene-1-sulfonyl chloride → HCID 178504713, compound

HRID 25445Notes

Reaction equation

HRID 25445 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11](Cl)(=[O:13])=[O:12])(=[O:4])=[O:3].[NH2:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][N:20]=[C:19]2[C:25]#[C:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>N1C=CC=CC=1.O>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][N:20]=[C:19]2[C:25]#[C:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)(=[O:13])=[O:12])(=[O:4])=[O:3]

Participants

5

Reactant 2

HCID 27351782-Methanesulfonylbenzene-1-sulfonyl chlorideHCID 178507359HCID 178507359, compound

Product 1

HCID 178504713HCID 178504713, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

2-Methylsulfonyl-N-(3-phenylethynyl-1H-indazol-5-yl)benzenesulfonamide can be obtained in the following way: 0.23 g of 2-methylsulfonylbenzenesulfonyl chloride is added to a solution, at a temperature in the region of 0° C. and under argon, of 0.2 g of 5-amino-3-phenylethynyl-1H-indazole in 3.5 ml of pyridine. The reaction mixture is then stirred for 1.5 hours at 0° C. and then 2 hours at a temperature in the region of 20° C., and is then diluted with 10 ml of water. After settling out, the aqueous phase is washed with 3 times 15 ml of ethyl acetate. The organic extracts are pooled, washed with 3 times 5 ml of water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 20° C. The residue thus obtained is purified by chromatography under argon pressure (50 kPa), on a cartridge of 25 g of silica (particle size 20-40 μm), eluting with pure dichloromethane then successively with dichloromethane/methanol (99.5/0.5; 99/1 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 20° C. The residue is recrystallized from 5 ml of isopropanol in the presence of 3S black. The crystals are filtered through sintered glass, washed with diisopropyl ether, partially dried, and then dried under reduced pressure (3 kPa) at a temperature in the region of 50° C. for 2 hours. 66 mg of 2-methylsulfonyl-N-(3-phenylethynyl-1H-indazol-5-yl)benzenesulfonamide are obtained in the form of an off-white powder melting at 198° C. (analysis C22H17N3O4S2 % calculated C, 58.52; H, 3.79; N, 9.31; O, 14.17; S, 14.20. % found C, 58.37; H, 3.88; N, 9.11; S, 13.73).

Workup

  1. washthe aqueous phase is washed with 3 times 15 ml of ethyl acetate
  2. washwashed with 3 times 5 ml of water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 20° C
  6. customThe residue thus obtained
  7. customis purified by chromatography under argon pressure (50 kPa)
  8. washon a cartridge of 25 g of silica (particle size 20-40 μm), eluting 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 20° C
  11. customThe residue is recrystallized from 5 ml of isopropanol in the presence of 3S black
  12. filtrationThe crystals are filtered through sintered glass
  13. washwashed with diisopropyl ether
  14. custompartially dried
  15. customdried under reduced pressure (3 kPa) at a temperature in the region of 50° C. for 2 hours

Sources & evidence

ORD record
ord-5a1619af1ee84b1cbb7bdd2e9ce26b4e
Source dataset
uspto-grants-2005_02
Patent number
US06858638B2

Reaction notes

Loading…