Lithium Chloride → 5-[4-Fluoro-3-(pyridin-2-yl)phenyl]-3-(pyridin-2-yl)-[1,2,4]triazine

HRID 1064284Notes

Reaction equation

HRID 1064284 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11](SC)[N:12]=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)CCC.[Cl-].[Li+]>O1CCOCC1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[N:10]=[C:11]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:12]=[N:13][CH:14]=2)=[CH:3][C:2]=1[C:24]1[CH:25]=[CH:26][CH:27]=[CH:22][N:23]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 6077842-(Tributylstannyl)pyridineHCID 222735835-(3-Bromo-4-fluorophenyl)-3-methylsulfanyl-[1,2,4]triazine

Product 1

HCID 104717605-[4-Fluoro-3-(pyridin-2-yl)phenyl]-3-(pyridin-2-yl)-[1,2,4]triazineYield 15.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 5-(3-bromo-4-fluorophenyl)-3-methylsulfanyl-[1,2,4]triazine (0.2 g, 0.67 mmol), cuprous 3-methylsalicylate (0.315 g, 1.5 mmol), 2-(tri-n-butylstannyl)pyridine (0.736 g, 2.2 mmol) and lithium chloride (0.085 g, 2.0 mmol) in dry 1,4-dioxane (8 ml) was added tetrakis(triphenylphosphine)palladium(0) (0.077 g, 0.032 mmol) and the mixture heated at 60° C. Fog 24 h. The reaction was allowed to cool to ambient temperature, diluted with DCM (20 ml) and washed with 10% ammonia solution (10 ml). The organic layer was washed with water (40 ml) and the combined organics dried over Mg2SO4, filtered and the solvent removed at reduced pressure. The crude product was purified by preparative thin-layer chromatography on silica gel, eluent 3% methanol in dichloromethane. The solid obtained was triturated with diethyl ether to give 5-[4-fluoro-3-(pyridin-2-yl)phenyl]-3-(pyridin-2-yl)-[1,2,4]triazine as a powdery orange solid (35 mg): δH (400 MHz, CDCl3) 7.39-7.48 (3H, m), 7.51 (1H, m), 7.81-8.00 (3H, m), 8.47 (1H, m), 8.71 (1H, m), 8.80 (1H, m), 8.93 (1H, m), 9.81 (1H, s); m/z (ES+) 330 (M++H).

Workup

  1. customFog 24 h
  2. temperatureto cool to ambient temperature
  3. washwashed with 10% ammonia solution (10 ml)
  4. washThe organic layer was washed with water (40 ml)
  5. dry with materialthe combined organics dried over Mg2SO4
  6. filtrationfiltered
  7. customthe solvent removed at reduced pressure
  8. customThe crude product was purified by preparative thin-layer chromatography on silica gel, eluent 3% methanol in dichloromethane
  9. customThe solid obtained
  10. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-b2d46a9800134332adf2b1fb1fd5bfd9
Source dataset
uspto-grants-2005_11
Patent number
US06969716B2

Reaction notes

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