Cesium carbonate → 6-chloro-2-methyl-4-(5-(trifluoromethyl)pyrazin-2-ylamino)pyridazin-3(2H)-one

HRID 449570Notes

Reaction equation

HRID 449570 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[N:4]=[CH:5][C:6]([NH2:9])=[N:7][CH:8]=1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:17]1[CH:18]=[C:13]([NH:9][C:6]2[CH:5]=[N:4][C:3]([C:2]([F:1])([F:10])[F:11])=[CH:8][N:7]=2)[C:14](=[O:21])[N:15]([CH3:20])[N:16]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 133411155-(Trifluoromethyl)pyrazin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 667424416-chloro-2-methyl-4-(5-(trifluoromethyl)pyrazin-2-ylamino)pyridazin-3(2H)-oneYield 72%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-(trifluoromethyl)pyrazin-2-amine (146 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol), cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthine (77.7 mg, 0.13 mmol) in dioxane (10.0 ml) was added tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) and the reaction mixture purged with argon (3×) before being warmed to 90° C. for 18 hr. The mixture was cooled, diluted with dichloromethane and water (50 mL) and the layers separated. The aqueous phase was extracted with methylene chloride (2×25 mL). The organic phases were combined and dried over MgSO4. The mixture was filtered and evaporated and the residue purified via automated flash chromatography (Analogix, SF15-24 g column, 1%-10% methanol/dichloromethane gradient) to give 6-chloro-2-methyl-4-(5-trifluoromethyl-pyrazin-2-ylamino)-2H-pyridazin-3-one (197 mg, 72%) as a yellow solid: LC/MS m/e calculated for C10H7ClF3N5O [M]+305.03, observed 305.9

Workup

  1. customthe reaction mixture purged with argon (3×)
  2. temperatureThe mixture was cooled
  3. additiondiluted with dichloromethane and water (50 mL)
  4. customthe layers separated
  5. extractionThe aqueous phase was extracted with methylene chloride (2×25 mL)
  6. dry with materialdried over MgSO4
  7. filtrationThe mixture was filtered
  8. customevaporated
  9. customthe residue purified

Sources & evidence

ORD record
ord-39362ebe4a504cffb4586a5d744b588e
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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