Potassium Carbonate → azd4635

HRID 1771349Notes

Reaction equation

HRID 1771349 reaction equation
Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1.[Cl:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[C:19]([CH3:32])[N:18]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[Cl:16][C:17]1[CH:22]=[C:21]([C:2]2[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=2[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:20]=[C:19]([CH3:32])[N:18]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 467394142-Chloro-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86676117HCID 86676117, compound

Product 1

HCID 86676119azd4635Yield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

6-bromo-5-(4-fluorophenyl)-1,2,4-triazin-3-amine (1 molar eq.), 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-methylpyridine (1 molar eq.) and K2CO3 (1.5 molar eq.) are suspended in a mixture of 1,4-dioxane and water (2:1; 10 mL of solvent per gram of bromotriazine). The resulting mixture is degassed, treated with dichlorobis[di-tert-butyl(4-dimethylaminophenyl)phosphino]palladium(II) (2 mol %) and refluxed until full consumption of bromotriazine is observed by LCMS. The cooled reaction mixture is then diluted with water, extracted with DCM and passed through a phase separator. The organic phase is concentrated under reduced pressure and purified by gradient flash chromatography, eluting with mixtures of ethyl acetate and hexanes to afford 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine (61%).

Workup

  1. customThe resulting mixture is degassed
  2. additiontreated with dichlorobis[di-tert-butyl(4-dimethylaminophenyl)phosphino]palladium(II) (2 mol %)
  3. temperaturerefluxed until full consumption of bromotriazine
  4. customThe cooled reaction mixture
  5. extractionextracted with DCM
  6. concentrationThe organic phase is concentrated under reduced pressure
  7. custompurified by gradient flash chromatography
  8. washeluting with mixtures of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-27dda1bafae54ec5b6f6423913962571
Source dataset
uspto-grants-2016_02
Patent number
US09249130B2

Reaction notes

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