Potassium Iodide → 1-(2-(1,2,3,4-Tetrahydro-9H-pyrido[3,4-b]indol-2-yl)-1-ethyl)-1,3-dihydro-3,3-dimethyl-2H-indol-2-one

HRID 864475Notes

Reaction equation

HRID 864475 reaction equation
[CH3:1][C:2]1([CH3:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12]O)[C:3]1=[O:14].C(N(CC)CC)C.CS(Cl)(=O)=O.[CH2:28]1[C:40]2[NH:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]=2[CH2:31][CH2:30][NH:29]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].C(O)(=O)/C=C\C(O)=O>ClCCl.C(OCC)(=O)C>[CH2:28]1[C:40]2[NH:39][C:38]3[C:33]([C:32]=2[CH2:31][CH2:30][N:29]1[CH2:12][CH2:11][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]([CH3:15])([CH3:1])[C:3]1=[O:14])=[CH:34][CH:35]=[CH:36][CH:37]=3

Participants

10

Reactant 7

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 107838Tetrahydro-beta-carbolineHCID 444266Maleic AcidHCID 158173642-((3,3-Dimethyl)oxindolyl)ethanol

Product 1

HCID 442133101-(2-(1,2,3,4-Tetrahydro-9H-pyrido[3,4-b]indol-2-yl)-1-ethyl)-1,3-dihydro-3,3-dimethyl-2H-indol-2-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-((3,3-Dimethyl)oxindolyl)ethanol and triethylamine (1.1 equivalent) were dissolved in dichloromethane, cooled to 0° C. under nitrogen with stirring and methanesulfonyl chloride (1 equivalent) was added. The mixture was stirred for 30 minutes, washed with cold dilute hydrochloric acid, dried (MgSO4), filtered and concentrated to dryness. The resulting oil was dissolved in acetonitrile and added to a solution of tetrahydro-β-carboline (1 equivalent) containing potassium carbonate (2.5 equivalent) and potassium iodide (0.1 equivalent). The reaction mixture was heated under reflux for three days under nitrogen. The solvent was removed under reduced pressure and the residue taken up in ethyl acetate. This solution was washed (×2) with water, dried (MgSO4), filtered and concentrated to dry under reduced pressure. Chromatography on silica gel (eluent ethyl acetate/methanol) gave an oil which was taken up in ethyl acetate. Maleic acid (1 equivalent) was added. The solution was refrigerated for 12 hours and the white crystals collected to given 1-(2-(1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indol-2-yl)-1-ethyl)-1,3-dihydro-3,3-dimethyl-2H-indol-2-one as its monomaleate salt, melting point 156°-158° C.

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. washwashed with cold dilute hydrochloric acid
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. dissolutionThe resulting oil was dissolved in acetonitrile
  7. temperatureThe reaction mixture was heated
  8. temperatureunder reflux for three days under nitrogen
  9. customThe solvent was removed under reduced pressure
  10. washThis solution was washed (×2) with water
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto dry under reduced pressure
  15. customChromatography on silica gel (eluent ethyl acetate/methanol) gave an oil which
  16. customthe white crystals collected

Sources & evidence

ORD record
ord-39bc7ca708b14349b52cd1e3822068b4
Source dataset
uspto-grants-1996_10
Patent number
US05563147

Reaction notes

Loading…