Dimethylformamide → (+/-)-5-[(4-iodophenyl)methyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

Temperatur

50 °C

Ethyl 1-[(4-iodophenyl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate (2.0 g, 4.4 mmol), (±)-tetrahydro-2H-pyran-3-ylhydrazine hydrochloride [(Example 9, Step 2), 1.0 g, 6.6 mmol, 1.5 equiv], potassium carbonate (6.1 g, 44 mmol, 10 equiv), and mercury(II) chloride (1.2 g, 4.4 mmol, 1 equiv) were combined in 1,2-dimethoxyethane (20 mL) and N,N-dimethylformamide (4 mL) and stirred at ambient temperature for 1 hour. The mixture was warmed to 50° C. for 20 minutes, treated with additional potassium carbonate (1.0 g, 7.2 mmol, 1.6 equiv) and warmed to 60° C. for 30 minutes. The mixture was heated to 70° C. for 1 hour, cooled to ambient temperature, poured into water (200 mL) and ethyl acetate (200 mL) and filtered through a pad of Celite. The mixture was extracted with ethyl acetate (3×200 mL) and the combined organic extracts were washed with water (50 mL) and brine (50 mL), dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes; ethyl acetate), providing the titled compound as a red solid.

1. temperaturewarmed to 60° C. for 30 minutes
2. temperatureThe mixture was heated to 70° C. for 1 hour
3. temperaturecooled to ambient temperature
4. filtrationfiltered through a pad of Celite
5. extractionThe mixture was extracted with ethyl acetate (3×200 mL)
6. washthe combined organic extracts were washed with water (50 mL) and brine (50 mL)
7. dry with materialdried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes; ethyl acetate)

ORD-Eintrag

ord-9146ccba09fc45959d8ad4870a9000ab

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08293744B2