Bromobenzene → 2,8-Dimethyl-5-phenyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 715149Notes

Reaction equation

HRID 715149 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.Br[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O>CN(C=O)C.O.[Cu]I>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

8

Reactant 4

HCID 7961BromobenzeneHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-

Product 1

HCID 126299082,8-Dimethyl-5-phenyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.2 g, 1 mmol), bromobenzene (0.314 g, 2 mmol), K3PO4 (0.424 g, 2 mmol), CuI (19 mg, 0.1 mmol) and L-Proline (23 mg, 0.2 mmol) in dry DMF (3 mL) was stirred at 150° C. for 12 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-phenyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as an off white solid (83 mg). 1H NMR (HCl salt, CD3OD) d (ppm): 7.60 (t, 2H), 7.5 (t, 1H), 7.4 (d, 2H), 7.35 (s, 1H), 7.1 (d, 1H), 7.05 (d, 1H), 4.8 (d, 1H), 4.4 (d, 1H), 3.85-3.8 (m, 1H), 3.6-3.59 (m, 1H), 3.2-3.19 (m, 1H), 3.18 (s, 3H), 3-2.95 (m, 1H), 2.4 (s, 3H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford crude material, which
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-c20c4a05799849b0a41e7348f7817b25
Source dataset
uspto-grants-2015_11
Patent number
US09187471B2

Reaction notes

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