Sodium Carbonate → 7-[2,4-Difluoro-3-(pyridin-3-yl)phenyl]-3-trifluoromethylimidazo[1,2-b][1,2,4]triazine

HRID 891862Notes

Reaction equation

HRID 891862 reaction equation
Br[C:2]1[N:6]2[N:7]=[CH:8][C:9]([C:11]([F:14])([F:13])[F:12])=[N:10][C:5]2=[N:4][CH:3]=1.[F:15][C:16]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[C:20]([F:28])[CH:19]=[CH:18][C:17]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[F:28][C:20]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[C:16]([F:15])[CH:17]=[CH:18][C:19]=1[C:2]1[N:6]2[N:7]=[CH:8][C:9]([C:11]([F:14])([F:13])[F:12])=[N:10][C:5]2=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 116014167-Bromo-3-trifluoromethyl-imidazo[1,2-B][1,2,4]triazineHCID 222400962,4-Difluoro-3-(pyridin-3-yl)benzeneboronic acid

Product 1

HCID 99996397-[2,4-Difluoro-3-(pyridin-3-yl)phenyl]-3-trifluoromethylimidazo[1,2-b][1,2,4]triazineYield 55.9%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-bromo-3-trifluoromethylimidazo[1,2-b][1,2,4]triazine (0.1 g, 0.37 mmol), 2,4-difluoro-3-(pyridin-3-yl)benzeneboronic acid (132 mg, 0.56 mmol) and 2 M Na2CO3 (0.56 ml) in 1,2-dimethoxyethane (2 ml) was degassed for 10 min with a stream of nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.022 g) was added and the mixture was stirred under nitrogen at 80° C. for 12 h. After allowing to cool to ambient temperature, the mixture was diluted with ethyl acetate then partitioned between water (100 ml) and ethyl acetate (100 ml). The organic extracts were dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2.5% MeOH/CH2Cl2), to give 78 mg (55%) of the title compound: 1H NMR (400 MHz, CDCl3) δ 7.17–7.22 (1H, m), 7.37–7.41 (1H, m), 7.80 (1H, d, J 8.4), 8.10–8.16 (1H, m), 8.56 (1H, d, J 2.6), 8.62 (1H, dd, J 4.6, 1.5), 8.72 (1H, 8.74 (1H, s); MS (ES+) m/z 378 [M+H]+.

Workup

  1. customwas degassed for 10 min with a stream of nitrogen
  2. additionTetrakis(triphenylphosphine)palladium(0) (0.022 g) was added
  3. temperatureto cool to ambient temperature
  4. additionthe mixture was diluted with ethyl acetate
  5. customthen partitioned between water (100 ml) and ethyl acetate (100 ml)
  6. dry with materialThe organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by flash chromatography (silica gel, 2.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-18e1a1e09ebd4c19be65d051caca8639
Source dataset
uspto-grants-2006_02
Patent number
US07005431B2

Reaction notes

Loading…