1,10-Phenanthroline → 2,8-dimethyl-5-((6-methylpyridin-3-yl)ethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400622Notes

Reaction equation

HRID 1400622 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.C(=O)([O-])[O-].[K+].[K+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.Br[C:37]#[C:38][C:39]1[CH:40]=[CH:41][C:42]([CH3:45])=[N:43][CH:44]=1>C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2]>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([C:37]#[C:38][C:39]3[CH:44]=[N:43][C:42]([CH3:45])=[CH:41][CH:40]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

7

Reactant 4

HCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 120404695-(2-Bromoethynyl)-2-methylpyridine

Product 1

HCID 594549842,8-dimethyl-5-((6-methylpyridin-3-yl)ethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 4.5%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 1140TolueneSolvent2×

Procedure

To a stirred solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.14 g, 0.00070 mol) and copper sulfate (0.017 g, 0.00007 mol) in toluene (4 mL) was added potassium carbonate (0.193 g, 0.0014 mol) and 1,10-phenanthroline (0.025 g, 0.000014 mol). The reaction mixture was stirred for 5 min at RT. A solution of 5-(bromoethynyl)-2-methylpyridine (0.150 g, 0.00077 mol) in toluene (2 mL) was added to the reaction mixture. After addition, the reaction mixture was stirred for 12 h at 80° C. After completion of reaction (monitored by TLC), solvent was removed under reduced pressure, and the crude product was purified by column chromatography (4% MeOH:DCM as eluent on silica (100-200 mesh), diameter of column—5.0 cm, height of silica—approx. 5 inch). The product was further purified by preparative TLC to give the desired compound as a yellow colored oil (0.010 g, 4.5% yield). 2,8-Dimethyl-5-((6-methylpyridin-3-yl)ethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.01 g, 0.0000317 mol) was dissolved in THF (1.0 mL).

Workup

  1. additionAfter addition
  2. stirringthe reaction mixture was stirred for 12 h at 80° C
  3. customAfter completion of reaction (monitored by TLC), solvent
  4. customwas removed under reduced pressure
  5. customthe crude product was purified by column chromatography (4% MeOH:DCM as eluent on silica (100-200 mesh), diameter of column—5.0 cm, height of silica—approx. 5 inch)
  6. customThe product was further purified by preparative TLC

Sources & evidence

ORD record
ord-edf2e1666ea24b5eafb52cca626fb97b
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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