Sodium Carbonate → Indole

HRID 440926Notes

Reaction equation

HRID 440926 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2C1CCNCC1.N1C=CC(CCCCl)=N1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[NH:7]1[C:8]2[C:4](=[CH:3][CH:2]=[CH:10][CH:9]=2)[CH:5]=[CH:6]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 128313754-(5-chloro-[1H]-indol-3-yl)-piperidineHCID 178478457HCID 178478457, compound

Product 1

HCID 798Indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3.26 gm (14 mMol) 5-chloro-3-(4-piperidinyl)-1H-indole, 2.03 gm (14 mMol) 3-(1H-pyrazol-3-yl)-1-chloropropane and 3.71 gm (35 mMol) sodium carbonate in 76 mL dimethylformamide was heated at 100° C. for 18 hours. The reaction mixture was cooled to ambient and the solvent removed under reduced pressure. The residue was partitioned between water and dichloromethane, then the phases were separated. The organic phase was washed with water followed by saturated aqueous sodium chloride and the remaining organics were dried over sodium sulfate. The dichloromethane was removed under reduced pressure and the residual yellow oil subjected to flash silica gel chromatography, eluting with a gradient system of dichloromethane containing 0-10% methanol. Fractions shown to contain product were concentrated under reduced pressure to give 1.72 gm (35.9%) 5-chloro-3-<1-<3-<1H-pyrazol-4-yl>propyl>-4-piperidinyl>-1H-indole as a colorless foam. The oxalate salt was formed to give the title compound as a light yellow foam. m.p.=110° C. MS(m/e): 343(M+) Calculated for C19H32N4Cl·C2H2O4 : Theory: C, 58.27; H, 5.82; N, 12.94. Found: C, 58.07; H, 5.97; N, 12.88.

Workup

  1. temperatureThe reaction mixture was cooled to ambient and the solvent
  2. customremoved under reduced pressure
  3. customThe residue was partitioned between water and dichloromethane
  4. customthe phases were separated
  5. washThe organic phase was washed with water
  6. dry with materialthe remaining organics were dried over sodium sulfate
  7. customThe dichloromethane was removed under reduced pressure
  8. washeluting with a gradient system of dichloromethane containing 0-10% methanol
  9. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-bb58cceada394cb080686d78f2fcb00e
Source dataset
uspto-grants-1996_05
Patent number
US05521196

Reaction notes

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