Formaldehyde → 9-(2-cyclohexylethyl)-2,3,4,9-tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indole

HRID 2198291Notes

Reaction equation

HRID 2198291 reaction equation
[CH:1]1([CH2:7][CH2:8][N:9]2[C:17]3[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[C:11]([CH2:19][CH2:20][NH:21][CH3:22])=[CH:10]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:23](O)(C(F)(F)F)=O.C=O>C(#N)C>[CH:1]1([CH2:7][CH2:8][N:9]2[C:17]3[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[C:11]3[CH2:19][CH2:20][N:21]([CH3:23])[CH2:22][C:10]2=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 669116442-(1-(2-cyclohexylethyl)-5-methyl-1H-indol-3-yl)-N-methylethanamine

Product 1

HCID 442421119-(2-cyclohexylethyl)-2,3,4,9-tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

2-(1-(2-cyclohexylethyl)-5-methyl-1H-indol-3-yl)-N-methylethanamine (72 mg, 0.23 mmol) was dissolved in acetonitrile (2 mL) containing 5% TFA and the reaction mixture was refluxed. 37% aqueous formaldehyde (0.02 mL) was added to the reaction mixture and refluxed for additional 2 h, cooled to 25° C., concentrated under reduced pressure and partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was dried over sodium sulfate, evaporated under reduced pressure and the residue was purified by silica gel chromatography (eluent EtOAc/EtOH/NH3: 9/1/0.1) to obtain 9-(2-cyclohexylethyl)-2,3,4,9-tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indole (52 mg). The free base was converted into its oxalate salt by treatment of oxalic acid (1 equiv) in anhydrous THF. 1H NMR (DMSO): 7.5 (d, 1H), 7.4 (s, 1H), 6.9 (d, 1H), 4.3 (bs, 2H), 4.0 (t, 2H), 3.6 (bs, 2H), 2.8 (m, 5H), 2.3 (s, 3H), 1.8-0.7 (m, 13H).

Workup

  1. temperaturethe reaction mixture was refluxed
  2. temperaturerefluxed for additional 2 h
  3. concentrationconcentrated under reduced pressure
  4. custompartitioned between ethyl acetate and saturated aqueous NaHCO3
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customevaporated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (eluent EtOAc/EtOH/NH3: 9/1/0.1)

Sources & evidence

ORD record
ord-82593a50b9fb4adf8ff4fae02a2e9828
Source dataset
uspto-grants-2012_12
Patent number
US08338447B2

Reaction notes

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