Sodium Bicarbonate → 2-(3-Cyclobutoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Reaction was carried out in the same manner as in Example 2-(b) except for using 0.46 g (0.96 mmol) of 2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 31-(a) in place of 3-chloro-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one. After completion of the reaction, to the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate to neutralize the mixture, and the mixture was extracted with a mixed solvent (chloroform/methanol=9/1 (V/V)). The organic layer after separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. To the obtained solid were added methanol and 28% aqueous ammonia, and the mixture was stirred under room temperature for 3 hours. Then, the solution was concentrated under reduced pressure and the obtained solid was washed with chloroform and dried under reduced pressure to obtain 199 mg of the title compound as a white solid. (Yield: 60%)

1. customReaction
2. customAfter completion of the reaction
3. extractionthe mixture was extracted with a mixed solvent (chloroform/methanol=9/1 (V/V))
4. customThe organic layer after separation
5. washwas washed with a saturated aqueous solution of sodium chloride
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. additionTo the obtained solid were added methanol and 28% aqueous ammonia
9. concentrationThen, the solution was concentrated under reduced pressure
10. washthe obtained solid was washed with chloroform
11. customdried under reduced pressure

ORD record

ord-c1af78ebc2094308a66cc958a06dbfc1

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450319B2