Sodium Carbonate → 9-Fluoro-7-(5-fluoro-pyridin-3-yl)-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

HRID 1521674Notes

Reaction equation

HRID 1521674 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[N:8]1[C:13]([CH3:16])=[N:14][N:15]=[C:7]1[CH2:6][CH2:5]2.C(=O)([O-])[O-].[Na+].[Na+].B(O)(O)[C:24]1[CH:29]=[N:28][CH:27]=[C:26]([F:30])[CH:25]=1>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:12][C:10]1[CH:11]=[C:2]([C:24]2[CH:29]=[N:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH:3]=[C:4]2[C:9]=1[N:8]1[C:13]([CH3:16])=[N:14][N:15]=[C:7]1[CH2:6][CH2:5]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 709780527-Bromo-9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

Product 1

HCID 709779699-Fluoro-7-(5-fluoro-pyridin-3-yl)-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

7-Bromo-9-fluoro-4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinoline (157-5, 0.25 g, 0.89 mmol) was dissolved in toluene (6.3 mL), and an aqueous 2.0 M sodium carbonate solution (2.8 mL), an ethanolic solution (2.8 mL) of 5-fluoropyridin-3-yl-3-boronic acid (0.19 g, 1.33 mmol) and tetrabutylammonium bromide (0.29 g, 0.89 mmol) were added. The mixture was deoxygenated under reduced pressure and flushed with nitrogen. After having repeated this cycle several times catalyst Pd(OAc)2 (0.01 g, 5 mol %) was added and the resulting suspension was heated under reflux for 18 h. After cooling, ethyl acetate (10 mL) and water (10 mL) were added and the organic layer was separated. The water phase was extracted with ethyl acetate (2×10 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered over a short plug of CELITE and evaporated under reduced pressure. The crude compound was purified by flash chromatography on silica gel to obtain title compound (white solid); 1H NMR (CDCl3, 500 MHz) δ 8.67 (t, J=1.5 Hz, 1H), 8.52 (d, J=2.7 Hz, 1H), 7.59 (ddd, J=2.0, 2.6 Hz, JHF=9.2 Hz, 1H), 7.39 (dd, J=1.9 Hz, JHF=14.6 Hz, 1H), 7.41 (d, J=1.7 Hz, 1H), 3.13 (t, J=7.5 Hz, 2H), 3.04 (t, J=7.5 Hz, 2H), 2.65 (d, JHF=8.3 Hz, 3H); MS (ESI): m/z=299 [M+H]+.

Workup

  1. customThe mixture was deoxygenated under reduced pressure
  2. customflushed with nitrogen
  3. additionwas added
  4. temperaturethe resulting suspension was heated
  5. temperatureunder reflux for 18 h
  6. temperatureAfter cooling
  7. additionethyl acetate (10 mL) and water (10 mL) were added
  8. customthe organic layer was separated
  9. extractionThe water phase was extracted with ethyl acetate (2×10 mL)
  10. washThe combined organic phases were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered over a short plug of CELITE
  13. customevaporated under reduced pressure
  14. customThe crude compound was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-1ebedc0fdbf74b808f5f41fc4b4066c7
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

Loading…