Acetyl chloride → 2-(3-Cyclopropoxy-4-difluoromethoxyphenyl)-3-methoxymethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Temperature

50 °C

To 8 ml of methanol was added 1.3 ml (18.3 mmol) of acetyl chloride, and the mixture was stirred at 50° C. for 15 minutes, and then, cooled to room temperature. To the solution was added 140 mg (0.276 mmol) of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-methoxymethyl-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 11-(b), and the resulting mixture was stirred at room temperature for 3 hours. After completion of the reaction, to the reaction mixture were successively added 18.4 ml of methanol solution containing 1M sodium methoxide and then water, and the mixture was extracted with a mixed solvent (chloroform:methano1=9:1 (UV)). The organic layer after separation of liquids was washed with water, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. Water was added to the obtained concentrate, and precipitated solid was collected by filtration and dried under reduced pressure to obtain 58 mg of the title compound as a white solid.

1. temperaturecooled to room temperature
2. stirringthe resulting mixture was stirred at room temperature for 3 hours
3. customAfter completion of the reaction
4. extractionwater, and the mixture was extracted with a mixed solvent (chloroform:methano1=9:1 (UV))
5. customThe organic layer after separation of liquids
6. washwas washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. additionWater was added to the obtained
10. concentrationconcentrate
11. customprecipitated solid
12. filtrationwas collected by filtration
13. customdried under reduced pressure

ORD record

ord-ad7cdcd79332400f8fa4d7ff8201e033

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450319B2