Propargyl bromide → 6-Cyclopropyl-4-methoxy-3-(2-methylphenoxy)pyridazine

HRID 1821682Notes

Reaction equation

HRID 1821682 reaction equation
[CH:1]12BC(C[CH2:7][CH2:8]1)CCC2.C(Br)C#C.[OH-].[Na+].Cl[C:17]1[N:22]=[N:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])=[C:19]([O:31][CH3:32])[CH:18]=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.O1CCCC1>[CH:7]1([C:17]2[N:22]=[N:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH3:30])=[C:19]([O:31][CH3:32])[CH:18]=2)[CH2:8][CH2:1]1

Participants

8

Reactant 4

HCID 7842Propargyl bromideHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 229401366-Chloro-4-methoxy-3-(2-methylphenoxy)pyridazine

Product 1

HCID 229400116-Cyclopropyl-4-methoxy-3-(2-methylphenoxy)pyridazineYield 70.7%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a tetrahydrofuran solution (2.94 mL) containing of 9-borabicyclo[3.3.1]nonane (0.5 mol/l, 1.47 mmol) was added 87.5 mg (0.735 mmol) of propargyl bromide, and the resulting mixture was refluxed for 2 hours. The reaction mixture was cooled to room temperature, 0.74 mL (2.2 mmol) of 3 mol/L aqueous sodium hydroxide solution was added to the mixture, and the resulting mixture was stirred at room temperature for 70 minutes. To the mixture were successively added 168 mg (0.669 mmol) of 6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in Example 2 (1) and 38.7 mg (0.00334 mmol) of tetrakis(triphenylphosphine)-palladium, and the resulting mixture was refluxed overnight. The reaction mixture was allowed to stand for cooling, water was added to the mixture, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, and washed successively with water and brine. After drying over anhydrous sodium sulfate, the solvent was removed. The obtained residue was purified by silica gel column chromatography to obtain 121 mg (0.473 mmol, Yield: 70.1%) of 6-cyclopropyl-4-methoxy-3-(2-methylphenoxy)pyridazine.

Workup

  1. temperaturethe resulting mixture was refluxed for 2 hours
  2. temperaturethe resulting mixture was refluxed overnight
  3. temperaturefor cooling
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washwashed successively with water and brine
  6. dry with materialAfter drying over anhydrous sodium sulfate
  7. customthe solvent was removed
  8. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-51ed4ad8abbb44028d3d22303f3ac1df
Source dataset
uspto-grants-2009_10
Patent number
US07608563B2

Reaction notes

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