2,5-Dibromopyridine → 5-[2-(6-Bromo-pyridin-3-yl)-1-fluoro-vinyl]-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400561Notes

Reaction equation

HRID 1400561 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:18][C:19]1[CH:24]=[CH:23][C:22](Br)=[CH:21][N:20]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-:43]>O>[Br:18][C:19]1[N:20]=[CH:21][C:22]([CH:2]=[C:1]([N:3]2[C:11]3[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[C:5]3[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]2=3)[F:43])=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 693532,5-DibromopyridineHCID 2724141Tetrabutylammonium FluorideHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 866909535-[2-(6-Bromo-pyridin-3-yl)-1-fluoro-vinyl]-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

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 (113 mg, 0.50 mmol), 2,5-dibromopyridine (100 mg, 0.42 mmol), dichlorobistriphenylphosphine palladium (II) (8 mg, 0.012 mmol) and TBAF.3H2O (396 mg, 1.26 mmol) were charged in a reaction vessel and heated at 80° C. for 5 min in microwave. After completion of reaction (as monitored by TLC & LCMS) the reaction mixture was poured into water (10 mL) and the desired compound extracted with EtOAc (20 mL×2). The organic layer was dried over sodium sulfate, concentrated under vacuum and purified by reverse phase chromatography to obtain 20 mg of 5-[2-(6-Bromo-pyridin-3-yl)-1-fluoro-vinyl]-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. 1H NMR (CD3OD, HCl salt) δ (ppm): 8.62 (s, 1H), 8.08 (d, 1H), 7.78 (d, 1H), 7.41 (d, 1H), 7.24 (s, 1H), 7.16 (d, 1H), 6.10 (d, 1H), 4.62 (d, 2H), 4.30 (d, 1H), 3.80 (m, 1H), 3.50 (m, 2H), 3.05 (s, 3H), 2.38 (s, 3H).

Workup

  1. addition3H2O (396 mg, 1.26 mmol) were charged in a reaction vessel
  2. customAfter completion of reaction (as monitored by TLC & LCMS) the reaction mixture
  3. extractionthe desired compound extracted with EtOAc (20 mL×2)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-c1dd362468f74e909841ce389170ac96
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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