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

HRID 1400564Notes

Reaction equation

HRID 1400564 reaction equation
[C:1]([N:3]1[C:11]2[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=2[C:5]2[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]1=2)#[CH:2].Br[C:19]1[CH:20]=[CH:21][C:22]([CH3:25])=[N:23][CH:24]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O>[CH3:17][N:14]1[CH2:15][CH2:16][C:4]2[N:3]([C:1]#[C:2][C:19]3[CH:24]=[N:23][C:22]([CH3:25])=[CH:21][CH:20]=3)[C:11]3[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[C:5]=2[CH2:13]1

Participants

5

Reactant 3

HCID 12010205-Bromo-2-methylpyridineHCID 2724141Tetrabutylammonium FluorideHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 594549842,8-dimethyl-5-((6-methylpyridin-3-yl)ethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 14.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (156 mg, 0.69 mmol), 5-bromo-2-methyl-pyridine (100 mg, 0.58 mmol), dichlorobistriphenylphosphine palladium (II) (12 mg, 0.017 mmol) and TBAF.3H2O (548 mg, 1.74 mmol) were added to a reaction vessel and the contents heated at 80° C. for 5 min in microwave. After completion of starting material (as monitored by TLC & LCMS), the reaction mixture was poured into water (25 mL) and the desired compound extracted with EtOAc (3×50 mL). The organic layer was dried over sodium sulfate, concentrated under vacuum and purified by reverse phase chromatography to obtain 27 mg of 2,8-dimethyl-5-(6-methyl-pyridin-3-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and mg of 5-[1-fluoro-2,2-bis-(6-methyl-pyridin-3-yl)-vinyl]-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. 1H NMR (CDCl3, free base) δ (ppm): 8.58 (s, 1H), 7.98 (s, 1H), 7.58 (d, 1H), 7.20 (d, 1H), 7.10 (d, 2H), 7.0 (d, 1H), 6.96 (d, 1H), 6.82 (d, 1H), 3.62 (m, 2H), 2.90-2.70 (m, 4H), 2.60 (s, 3H), 2.50 (s, 3H), 2.40 (s, 6H).

Workup

  1. addition3H2O (548 mg, 1.74 mmol) were added to a reaction vessel
  2. extractionthe desired compound extracted with EtOAc (3×50 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-14cc8de5eedb458c8763698f569094c2
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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