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

HRID 1775906Notes

Reaction equation

HRID 1775906 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH3:14])[CH:12]=2)[N:7]([CH2:15][CH2:16][C:17]2[CH:18]=[N:19][C:20]([CH3:23])=[CH:21][CH:22]=2)[CH:6]=1.[C:24](O)(C(F)(F)F)=O.C=O>C(#N)C>[CH3:1][N:2]1[CH2:3][CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([CH3:14])[CH:12]=3)[N:7]([CH2:15][CH2:16][C:17]3[CH:18]=[N:19][C:20]([CH3:23])=[CH:21][CH:22]=3)[C:6]=2[CH2:24]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 66911655N-methyl-2-(5-methyl-1-(2-(6-methylpyridin-3-yl)ethyl)-1H-indol-3-yl)ethanamine

Product 1

HCID 442421102,3,4,9-tetrahydro-2,6-dimethyl-9-(2-(6-methylpyridin-3-yl)ethyl)-1H-pyrido[3,4-b]indole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

N-methyl-2-(5-methyl-1-(2-(6-methylpyridin-3-yl)ethyl)-1H-indol-3-yl)ethanamine (150 mg) was dissolved in acetonitrile (4 mL) containing 5% TFA and the reaction mixture was refluxed. 37% aqueous formaldehyde (0.04 mL) was added and the reaction mixture was refluxed for additional 1.5 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 Methanol: aqueous NH3, 95:5) to obtain 2,3,4,9-tetrahydro-2,6-dimethyl-9-(2-(6-methylpyridin-3-yl)ethyl)-1H-pyrido[3,4-b]indole. The free base was converted into its dihydrochloride salt by treatment of dioxane-HCl. 1H NMR (DMSO): 11.7 (bs, 1H), 8.6 (s, 1H), 8.3 (d, 1H), 7.7 (d, 1H), 7.3 (d, 1H), 7.25 (s, 1H), 6.9 (d, 1H), 4.8 (m, 1H), 4.4 (m, 1H), 4.35 (t, 2H), 3.7 (bs, 1H), 3.55 (s, 3H), 3.5 (m, 1H), 3.4 (bs, 1H), 3.1 (t, 2H), 3.05 (bs, 1H), 2.65 (s, 3H), 2.35 (s, 3H).

Workup

  1. temperaturethe reaction mixture was refluxed
  2. temperaturethe reaction mixture was refluxed for additional 1.5 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 Methanol: aqueous NH3, 95:5)

Sources & evidence

ORD record
ord-55c15d5793dc4806960ede24e2eb89a6
Source dataset
uspto-grants-2016_02
Patent number
US09260429B2

Reaction notes

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