2-Methanesulfonylbenzene-1-sulfonyl chloride → HCID 22567026, compound

HRID 25449Notes

Reaction equation

HRID 25449 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)[N:21]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:20]=[C:19]2[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=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)[N:21]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:30])[CH3:31])[N:20]=[C:19]2[CH2:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)(=[O:13])=[O:12])(=[O:4])=[O:3]

Participants

5

Reactant 2

HCID 27351782-Methanesulfonylbenzene-1-sulfonyl chlorideHCID 225671855-amino-3-phenethyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole

Product 1

HCID 22567026HCID 22567026, compoundYield 42.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

2-Methylsulfonyl-N-[3-phenethyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazol-5-yl]benzenesulfonamide can be obtained in the following way: 0.6 g 2-methylsulfonylbenzenesulfonyl chloride is added portionwise to a solution, at a temperature in the region of 0° C. and under argon, of 0.83 g of 5-amino-3-phenethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole in 13 ml of pyridine. The reaction mixture is then stirred for 0.5 hours at a temperature in the region of 0° C. then 2 hours at a temperature in the region of 20° C., and is then diluted with 13 ml of water. After settling out, the aqueous phase is extracted with 3 times 30 ml of ethyl acetate. The organic extracts are pooled, washed with 2 times 15 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 40° C. The residue thus obtained is purified by chromatography under argon pressure (50 kPa), on a cartridge of 70 g of silice (particle size 20-40 μm), eluting successively with pure cyclohexane then with a cyclohexane/ethyl acetate (80/20 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 25° C. 0.56 g of 2-methylsulfonyl-N-[3-phenethyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazol-5-yl]benzenesulfonamide are obtained in the form of a brown-colored paste (Rf=0.32, silica gel thin layer chromatography, eluent: cyclohexane/ethyl acetate (70/30 by volume)).

Workup

  1. extractionthe aqueous phase is extracted with 3 times 30 ml of ethyl acetate
  2. washwashed with 2 times 15 ml of a saturated aqueous sodium chloride solution
  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 40° C
  6. customThe residue thus obtained
  7. customis purified by chromatography under argon pressure (50 kPa)
  8. washon a cartridge of 70 g of silice (particle size 20-40 μm), eluting successively with pure cyclohexane
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 25° C

Sources & evidence

ORD record
ord-5aa91b8900fa46b68110dca610e61e25
Source dataset
uspto-grants-2005_02
Patent number
US06858638B2

Reaction notes

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