Methanol → 1-(cyclopropylmethyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 333730Notes

Reaction equation

HRID 333730 reaction equation
[CH3:1][O:2][C:3]1[C:4]([OH:20])=[C:5]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=[CH:11][CH:10]=2)[N:6]=[N:7][CH:8]=1.[H-].[Na+].Br[CH2:24][CH:25]1[CH2:27][CH2:26]1.CO>CN(C)C=O>[CH:25]1([CH2:24][N:7]2[CH:8]=[C:3]([O:2][CH3:1])[C:4](=[O:20])[C:5]([C:9]3[N:13]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[N:12]=[CH:11][CH:10]=3)=[N:6]2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 178493808HCID 178493808, compound

Product 1

HCID 680148501-(cyclopropylmethyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under an argon atmosphere, to a solution of 5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4-ol (2.0 g) in dimethylformamide (40 mL) was added 60% sodium hydride (596 mg) with stirring under ice-cooling, and the mixture was stirred at the same temperature for 1.5 hr. Then, (bromomethyl)cyclopropane (1.085 mL) was added, and the mixture was stirred at room temperature for 16 hr. To the reaction mixture was added methanol, and the mixture was concentrated under reduced pressure to dryness. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) and crystallized from methanol/ethyl acetate to give the title compound (2.12 g) as white prisms.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 1.5 hr
  3. stirringthe mixture was stirred at room temperature for 16 hr
  4. concentrationthe mixture was concentrated under reduced pressure to dryness
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol)
  6. customcrystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-aafd060bb8214724bc14d107f6b14dab
Source dataset
uspto-grants-2014_11
Patent number
US08883788B2

Reaction notes

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