Sodium hydride → 3-Bromo-2,4-dimethyl-6-(3-methyl-pyrazol-1-yl)-pyridine

HRID 1711156Notes

Reaction equation

HRID 1711156 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][NH:4][N:3]=1.[H-].[Na+].Cl[C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([Br:17])=[C:12]([CH3:18])[N:11]=1>CN(C=O)C.CCOC(C)=O.[Cl-].[Na+].O>[Br:17][C:13]1[C:12]([CH3:18])=[N:11][C:10]([N:4]2[CH:5]=[CH:6][C:2]([CH3:1])=[N:3]2)=[CH:15][C:14]=1[CH3:16]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 714643513-Bromo-6-chloro-2,4-dimethylpyridineHCID 178428694HCID 178428694, compound

Product 1

HCID 687775833-Bromo-2,4-dimethyl-6-(3-methyl-pyrazol-1-yl)-pyridineYield 63%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 3-methylpyrazole (156 mg, 1.90 mmol) in DMF (2 ml) was added NaH (60% dispersion in oil, 76 mg, 1.9 mmol) and the reaction stirred at room temperature for 30 min. before adding 2-chloro-5-bromo-4,6-dimethylpyridine (227 mg, 1.03 mmol) as a solid in one portion. The mixture was heated to 85° C. for 2 d then cooled and diluted with EtOAc (35 ml) and brine (20 ml). The organic layer was washed with brine (2×15 ml) and water (1×10 ml), dried (Na2SO4), concentrated and purified by column chromatography on silica gel (Hexanes/Et2O, 9:1) to afford 3-bromo-2,4-dimethyl-6-(3-methyl-pyrazol-1-yl)-pyridine (172 mg, 63%) as a white crystalline solid. 1H NMR (CDCl3) δ 2.36 (s, 3H), 2.44 (s, 3H), 2.65 (s, 3H), 6.23 (d, 1H, J=3 Hz), 7.62 (s, 1H), 8.41 (d, 1H, J=3 Hz).

Workup

  1. temperatureThe mixture was heated to 85° C. for 2 d
  2. temperaturethen cooled
  3. washThe organic layer was washed with brine (2×15 ml) and water (1×10 ml)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by column chromatography on silica gel (Hexanes/Et2O, 9:1)

Sources & evidence

ORD record
ord-6f776a1beba24283a55c2629d42633a7
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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