Formaldehyde → 9-(4-fluorophenethyl)-6-chloro-2,3,4,9-tetrahydro-2-methyl-1H-pyrido[3,4-b]indole

HRID 1775913Notes

Reaction equation

HRID 1775913 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[C:10]([CH2:18][CH2:19][NH:20][CH3:21])=[CH:9]2)=[CH:4][CH:3]=1.[C:24](O)(C(F)(F)F)=O.C=O>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[C:10]3[CH2:18][CH2:19][N:20]([CH3:24])[CH2:21][C:9]2=3)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 669117692-(1-(4-fluorophenethyl)-5-chloro-1H-indol-3-yl)-N-methylethanamine

Product 1

HCID 442421769-(4-fluorophenethyl)-6-chloro-2,3,4,9-tetrahydro-2-methyl-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. 2-(1-(4-fluorophenethyl)-5-chloro-1H-indol-3-yl)-N-methylethanamine (600 mg) was dissolved in acetonitrile (10 mL) containing 5% TFA and the reaction mixture was heated to reflux. 37% aqueous formaldehyde (0.17 mL) was added and the reflux was continued for 15-20 min. 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 6% methanol-chloroform) to obtain 170 mg of product. The free base was converted into its HCl salt by treatment of HCL-ether. 1H NMR (CDCl3) δ 13.1 (s, 1H), 7.25-7.1 (m, 3H), 6.8 (m, 2H), 6.7 (m, 2H), 4.4 (m, 1H), 4.2 (m, 1H), 3.9 (m, 1H), 3.4 (m, 1H), 3.2-3.0 (m, 3H), 2.8 (m, 3H), 2.6 (s, 3H). MS m/z observed 343. HPLC RT 5.16 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 6% methanol-chloroform)

Sources & evidence

ORD record
ord-65e5f85bf9f248c89efa65fede3e76bc
Source dataset
uspto-grants-2016_02
Patent number
US09260429B2

Reaction notes

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