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

HRID 1775905Notes

Reaction equation

HRID 1775905 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.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.Cl.O1CCOCC1>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

7

Reactant 5

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 204431481,4-Dioxane hydrochlorideHCID 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

The title compound was prepared by General Method 4. 150 mg of N-methyl-2-(5-methyl-1-(2-(6-methylpyridin-3-yl)ethyl)-1H-indol-3-yl)ethanamine was dissolved in acetonitrile (4 mL) containing 5% TFA and the reaction mixture was heated to reflux. 37% aqueous formaldehyde (0.04 mL) was added and the reflux was continued for additional 1.5 h. The reaction mixture was cooled to 25° C., concentrated under reduced pressure and partitioned between ethyl acetate and satd. 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 the product. The free base was converted into its dihydrochloride salt by treatment of dioxane-HCl. 1H NMR (DMSO) δ 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 (3, 3H), 2.35 (s, 3H). MS m/z observed 320. HPLC RT 3.63 min.

Workup

  1. temperaturethe reaction mixture was heated to reflux
  2. concentrationconcentrated under reduced pressure
  3. custompartitioned between ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customthe residue was purified by silica gel chromatography (eluent Methanol:aqueous NH3, 95:5)
  7. customto obtain the product

Sources & evidence

ORD record
ord-320190e28feb4ea99986ce54b387aa48
Source dataset
uspto-grants-2016_02
Patent number
US09260429B2

Reaction notes

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