Benzenesulfonyl chloride → HCID 10156873, compound

HRID 1766275Notes

Reaction equation

HRID 1766275 reaction equation
C[N:2]1[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[C:4]([CH:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[CH:3]1.[H-].[Na+].[C:21]1([S:27](Cl)(=[O:29])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:31](OCC)(=O)C>C1COCC1.C(OCC)C>[CH3:31][C:9]1[CH:8]=[C:7]([O:11][S:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:29])=[O:28])[CH:6]=[C:5]2[C:10]=1[NH:2][CH:3]=[C:4]2[CH:12]1[CH2:13][CH2:14][N:15]([CH3:18])[CH2:16][CH2:17]1

Participants

7

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 179801241-Methyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-ol

Product 1

HCID 10156873HCID 10156873, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-4 °C

Procedure

To a suspension of 1-methyl-3-(1-methylpiperdin-4-yl)-5-hydroxy-1H-indole (2.52 mmol, 0.616 g) in THF (6.4 mL) at room temperature was added 60% sodium hydride (3.03 mmol, 0.121 g). After stirring 15 minutes, benzenesulfonyl chloride (2.77 mmol, 0.490 g) was added. Reaction stirred at room temperature for 24 hours. Reaction then treated with ethyl acetate (25 mL) and washed with water (2×25 mL) then brine (25 mL). The organic phase was dried over sodium sulfate, filtered, concentrated in vacuo to afford an oil. The oil was subjected to normal phase radial chromatography, 4 mm plate eluting with 9:1 chloroform:2M ammonia in methanol. Fractions containing product combined, concentrated in vacuo to afford an oil. The oil was dissolved in diethyl ether. The solution was cooled at −4° C. which resulted in crystal formation. Crystals collected by filtration to afford 0.639 g (66%) of the title compound: mp=118° C.; mass spectrum (ion spray): m/z=385 (M); 1H NMR (DMSOd6): 7.85-7.77 (m, 3H), 7.67-7.62 (m, 2H), 7.12 (d, J=2.20 Hz, 1H), 6.69 (d, J=2.20 Hz, 1H), 6.60 (d, J=1.46 Hz, 1H), 2.77-2.68 (bd, 2H), 2.43 (m, 1H), 2.37 (s, 3H), 2.19 (s, 3H), 1.92 (m, 2H), 1.71-1.62 (m, 2H), 1.52 (m, 2H); Calculated for C21H24N2O3S: C, 65.60; H, 6.29; N, 7.29. Found: C, 65.64; H, 6.45; N, 7.19.

Workup

  1. customReaction
  2. stirringstirred at room temperature for 24 hours
  3. customReaction
  4. washwashed with water (2×25 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford an oil
  9. washeluting with 9:1 chloroform
  10. additionFractions containing product
  11. concentrationconcentrated in vacuo
  12. customto afford an oil
  13. customresulted in crystal formation
  14. filtrationCrystals collected by filtration

Sources & evidence

ORD record
ord-a9eca62e2ea74dbaa7d293a2832475d3
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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