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

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).

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)

ORD record

ord-d36e0f922e244d378753680d2a771034

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260429B2