p-Toluenesulfonic acid → 8-fluoro-6-methoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1677053Notes

Reaction equation

HRID 1677053 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl.[NH:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1.C1(C(C2C=CC=CC=2)=N[NH:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=2[O:36][CH3:37])C=CC=CC=1>C(O)C>[F:35][C:32]1[CH:31]=[C:30]([O:36][CH3:37])[C:29]2[NH:28][C:16]3[CH2:15][CH2:14][NH:13][CH2:18][C:17]=3[C:34]=2[CH:33]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 30848514-Piperidone hydrochlorideHCID 86626061Diphenylmethanone (4-fluoro-2-methoxyphenyl)hydrazone

Product 1

HCID 575412988-fluoro-6-methoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

p-Toluenesulfonic acid (129 mg, 0.75 mmol) was added to piperidin-4-one hydrochloride (50.8 mg, 0.37 mmol) and 1-(diphenylmethylene)-2-(4-fluoro-2-methoxyphenyl)hydrazine (80.0 mg, 0.25 mmol) in ethanol (1.25 mL) at 25° C. over a period of 1 min under air. The resulting suspension was stirred at 80° C. for 16 hours. The reaction mixture was diluted with EtOH (20 mL), and EtOAC (100 mL) then washed sequentially with saturated NaHCO3 (75 mL), saturated NaHCO3 (75 mL), and saturated brine (75 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by preparative HPLC (containing 0.1% NH3, CH3CN/H2O) as eluents. Fractions containing the desired compound were evaporated to dryness to afford 8-fluoro-6-methoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (25.0 mg, 46%) as an off-white solid.

Workup

  1. washthen washed sequentially with saturated NaHCO3 (75 mL), saturated NaHCO3 (75 mL), and saturated brine (75 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by ion exchange chromatography
  7. washThe desired product was eluted from the column
  8. customwere evaporated to dryness
  9. customto afford crude product
  10. customThe crude product was purified by preparative HPLC (containing 0.1% NH3, CH3CN/H2O) as eluents
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b7979834682648c0b15148c03e326d54
Source dataset
uspto-grants-2011_08
Patent number
US08008279B2

Reaction notes

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