Pyridine → HCID 53855129, compound

HRID 843774Notes

Reaction equation

HRID 843774 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1.N1C=CC=CC=1.[C:24]1([S:30](Cl)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[OH-:31].[NH4+:1].[C:24]1([S:30]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 7369Benzenesulfonyl chlorideHCID 118312203-(1-Methylpiperidin-4-yl)-1h-indol-5-amine

Product 2

HCID 14923Ammonium HydroxideHCID 53855129HCID 53855129, compoundYield 78.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2.00 gm (5.74 mMol) 5-amino-3-(1-methylpiperidin-4-yl)-1H-indole in 50.0 mL dichloromethane were added 1.63 gm (20.7 mMol) pyridine and the solution was cooled to 0° C. To this cooled solution were then added dropwise a solution of 2.23 gm (12.6 mMol) benzenesulfonyl chloride in 50 mL dichloromethane. The reaction mixture was allowed to warm gradually to ambient. After 24 hours the reaction mixture was washed with 100 mL water and the remaining organics concentrated under reduced pressure. The residue was suspended in water and the pH adjusted to 14 with sodium hydroxide. The aqueous phase was then extracted well with dichloromethane. The organic phase was washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The aqueous phases were combined and the pH adjusted to 10 by the addition of acid and extracted again with 3:1 chloroform:isopropanol. These organic extracts were combined and concentrated under reduced pressure. The combined residues were subjected to flash chromtography, eluting with a gradient system of 100:10:0.5 to 100:11:0.5 dichloromethane:methanol:ammonium hydroxide, giving 0.83 gm (39.1%) of the title compound as a white powder.

Workup

  1. temperatureto warm gradually to ambient
  2. washAfter 24 hours the reaction mixture was washed with 100 mL water
  3. concentrationthe remaining organics concentrated under reduced pressure
  4. extractionThe aqueous phase was then extracted well with dichloromethane
  5. washThe organic phase was washed sequentially with water and saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionthe pH adjusted to 10 by the addition of acid
  9. extractionextracted again with 3:1 chloroform
  10. concentrationconcentrated under reduced pressure
  11. washeluting with a gradient system of 100:10:0.5 to 100:11:0.5 dichloromethane

Sources & evidence

ORD record
ord-529ba673b9454dc5b2f2180412ca04b0
Source dataset
uspto-grants-2002_04
Patent number
US06380201B1

Reaction notes

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