2,4-Dichloro-6-methylpyrimidine → HCID 117668859, compound

HRID 595181Notes

Reaction equation

HRID 595181 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH2:9])[CH:4]=1.[Cl:12][C:13]1[N:18]=[C:17](Cl)[CH:16]=[C:15]([CH3:20])[N:14]=1.CC(C)([O-])C.[Na+]>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:12][C:13]1[N:18]=[C:17]([NH:9][C:5]2[CH:4]=[C:3]([C:2]([F:1])([F:10])[F:11])[CH:8]=[CH:7][N:6]=2)[CH:16]=[C:15]([CH3:20])[N:14]=1

Participants

6

Reactant 3

HCID 794712,4-Dichloro-6-methylpyrimidineHCID 27783152-Amino-4-(trifluoromethyl)pyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 117668859HCID 117668859, compound

Reagents, catalysts & solvents 2

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

Procedure

Nitrogen was bubbled through a solution of 4-(trifluoromethyl)pyridin-2-amine (10.96 g, 67.6 mmol), 2,4-dichloro-6-methylpyrimidine (11.02 g, 67.6 mmol) in dioxane (198 mL) for 10 minutes. Sodium tert-butoxide (6.50 g, 67.6 mmol) and 1,1′ bis(di-t-butylphosphino ferrocene) (3.21 g, 6.76 mmol) were added, followed by Pd2(dba)3 (3.10 g, 3.38 mmol) and the solution was evacuated and then purged with nitrogen. After heating to reflux for 3 h, the reaction mixture was cooled to room temperature and EtOAc (1 L) was added. The organic layer was washed with saturated sodium bicarbonate, water and brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/hexanes; to afford 2-chloro-6-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine as a yellow solid. MS ESI calcd. for C11H18ClF3N4[M+H]+ 289. found 289.

Workup

  1. customthe solution was evacuated
  2. custompurged with nitrogen
  3. temperatureAfter heating
  4. temperatureto reflux for 3 h
  5. additionEtOAc (1 L) was added
  6. washThe organic layer was washed with saturated sodium bicarbonate, water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel (EtOAc/hexanes

Sources & evidence

ORD record
ord-c32c35806ae548b7875aae87c6f18e67
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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