1-Methyl-4-piperidone → 8-chloro-6-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400327Notes

Reaction equation

HRID 1400327 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]N)=[C:5]([F:11])[CH:4]=1.[CH3:12][N:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1>S(=O)(=O)(O)O.O1CCOCC1>[Cl:2][C:3]1[CH:4]=[C:5]([F:11])[C:6]2[NH:9][C:16]3[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][C:15]=3[C:7]=2[CH:8]=1

Participants

5

Reactant 2

HCID 740491-Methyl-4-piperidoneHCID 2782933(4-Chloro-2-fluorophenyl)hydrazine hydrochloride

Product 1

HCID 594550388-chloro-6-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

4-Chloro-2-fluorophenyl hydrazine hydrochloride (1 equiv.) is taken in 7% sulfuric acid in 1,4-dioxan. N-Methylpiperidine-4-one (0.76-1.4 equiv.) is added and the contents are stirred at RT for 10 min. The reaction mixture is then stirred at 100° C. for 6 h. The reaction is monitored by TLC and LCMS. After completion of the reaction, the reaction mixture is concentrated and then slowly quenched with aq. NaHCO3 solution, followed by extraction with EtOAc. The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The crude product is purified by column chromatography to afford 8-chloro-6-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole.

Workup

  1. stirringThe reaction mixture is then stirred at 100° C. for 6 h
  2. customAfter completion of the reaction
  3. concentrationthe reaction mixture is concentrated
  4. customslowly quenched with aq. NaHCO3 solution
  5. extractionfollowed by extraction with EtOAc
  6. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  7. customevaporated to dryness
  8. customThe crude product is purified by column chromatography

Sources & evidence

ORD record
ord-0d813c50fd7c40f78921045818161a92
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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