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

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.

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

ORD record

ord-51ed4ad8abbb44028d3d22303f3ac1df

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608563B2