2-Methyl-5-vinylpyridine → 8-Ethyl-2-methyl-5-[2-(6-methyl-pyridin-3-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 710813Notes

Reaction equation

HRID 710813 reaction equation
[CH2:1]([C:3]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:6]=3[C:5]=2[CH:4]=1)[CH3:2].[OH-].[K+].[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]=[CH2:27])=[CH:22][N:21]=1>CN1CCCC1=O.O>[CH2:1]([C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:27][CH2:26][C:23]3[CH:22]=[N:21][C:20]([CH3:19])=[CH:25][CH:24]=3)[C:7]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:6]=3[C:5]=2[CH:4]=1)[CH3:2]

Participants

6

Reactant 3

HCID 88172-Methyl-5-vinylpyridineHCID 14797Potassium HydroxideHCID 594550988-Ethyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 578761698-Ethyl-2-methyl-5-[2-(6-methyl-pyridin-3-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 20.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 8-Ethyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.107 g, 0.5 mmol) in N-methyl 2-pyrolidone (2 mL) was added powdered potassium hydroxide (0.224 g, 4.0 mmol) and allowed to stir for 10 min at RT. 2-methyl-5-vinyl pyridine (0.065 g, 0.55 mmol) was added and stirred for further 24 h. at 120 deg C., After completion of TLC, Reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3×50 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude was purified through column chromatography (8% MeOH:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch) to provide the desired compound as brown oil (0.034 g, 20% yield). 8-Ethyl-2-methyl-5-[2-(6-methyl-pyridin-3-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.034 g, 0.102 mmol) was dissolved in THF (0.5 mL). A solution of oxalic acid dihydrate (0.013 g, 0.102 mol) in THF (0.5 mL) was added and stirred for 30 min at RT, Precipitate obtained was filtered and dried to give oxalate salt as off white solid (0.015 g, 32% yield).

Workup

  1. stirringstirred for further 24 h. at 120 deg C
  2. custom, After completion of TLC, Reaction mixture
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified through column chromatography (8% MeOH:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch)

Sources & evidence

ORD record
ord-b3f13906479c406b99234f36f8d7ff85
Source dataset
uspto-grants-2015_11
Patent number
US09181240B2

Reaction notes

Loading…