Tetrabutylammonium Fluoride → (Z)-5-(2-fluoro-2-(6-methoxypyridin-3-yl)vinyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401643Notes

Reaction equation

HRID 1401643 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]([O:25][CH3:26])=[N:23][CH:24]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-:44]>O>[F:44]/[C:2](/[C:19]1[CH:24]=[N:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)=[CH: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

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 27348955-Bromo-2-methoxypyridineHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 59455275(Z)-5-(2-fluoro-2-(6-methoxypyridin-3-yl)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

5-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (285 mg, 0.00127 mol) and 5-bromo-2-methoxy-pyridine (200 mg, 0.001063 mol), dichlorobistriphenylphosphine palladium (II) (20 mg, 0.0000285 mol) and TBAF.3H2O (1 g, 0.00317 mol) were charged in a microwave tube. The reaction mixture was heated at 80° C. for 5 min in microwave. It was then cooled to RT. The reaction was monitored by TLC and LCMS. The reaction mixture was diluted with water (100 mL) and the compound extracted with EtOAc (3×30 mL). The combined organic layers were washed with water, dried over sodium sulfate and concentrated under vacuum to obtain the crude product, which was purified on neutral alumina (Eluent: 0-20%, Hexane/EtOAc). 2 mg of pure product was obtained as a liquid. 1H NMR (CDCl3, free base) δ (ppm): 8.22 (s, 1H), 7.92 (d, 1H), 7.36 (d, 1H), 7.20 (s, 1H), 7.04 (d, 1H), 6.80 (d, 1H), 5.70 (d, 1H), 3.68 (s, 2H), 3.92 (m, 2H), 3.88 (m, 2H), 2.60 (s, 3H), 2.42 (s, 3H).

Workup

  1. addition3H2O (1 g, 0.00317 mol) were charged in a microwave tube
  2. temperatureIt was then cooled to RT
  3. extractionthe compound extracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customto obtain the crude product, which
  8. customwas purified on neutral alumina (Eluent: 0-20%, Hexane/EtOAc)

Sources & evidence

ORD record
ord-4f4e25d8a56a4ee7a30276f91d416c70
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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