Methyl iodide → 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one

HRID 407698

Reaction equation

HRID 407698 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[H-].[Na+].I[CH3:20]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH3:20])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866839736-Chloro-2-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one

Product 1

HCID 585400026-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-oneYield 29.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 127a (480 mg, 2.0 mmol) in anhydrous DMF (10 mL) was added NaH (purity 60%) (64 mg, 1.6 mmol) at 0° C. and the resulting mixture was stirred for 0.5 h. To the mixture was added iodomethane (227 mg, 1.6 mmol) in DMF (5 mL) dropwise at 0° C. The reaction mixture was stirred for additional 1.5 h and quenched with water (20 mL). It was then extracted with dichloromethane (3×20 mL) and the combined organic layer was evaporated under reduced pressure. The residue was purified by reverse-phase Combiflush (A: 2% aqueous NH4HCO3, B: acetonitrile) to afford 127b (120 mg, 24%) as a light yellow solid. MS-ESI: [M+H]+ 254.3

Workup

  1. stirringThe reaction mixture was stirred for additional 1.5 h
  2. customquenched with water (20 mL)
  3. extractionIt was then extracted with dichloromethane (3×20 mL)
  4. customthe combined organic layer was evaporated under reduced pressure
  5. customThe residue was purified by reverse-phase Combiflush (A: 2% aqueous NH4HCO3, B

Sources & evidence

ORD record
ord-df70469246034d2fbdb1ae951893740c
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Linked notes

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