Chloroacetaldehyde → 2-Chloroimidazo[1,2-b]pyridazine

Temperatur

0 °C

Chloro-imidazo[1,2-b]pyridazine (10-1) was synthesized as shown in scheme 10, wherein chloracetaldehyde (55% in water, 126 ml, 880 mmol) was added to a solution of 6-chloro-pyridazin-3-ylamine (25.43 g, 196 mmol) and NaHCO3 (28 g, 334 mmol) in EtOH (600 ml) and then the reaction mixture was heated to reflux while stirring for 14 hours. The resulting dark brown reaction mixture was then concentrated under vacuum and the resulting residue reconstituted with dichloromethane (DCM). This solution was filtered through a celite pad and the solid washed with DCM and the solvent was then removed to yield a dark brown oil. 2M HCl (290 ml) and water (300 ml) was added to the residue and the resulting slurry was stirred at room temperature for 15 minutes. The solution was filtered through a celite pad and the filter cake was washed with water. The filtrate was extracted with diethyl ether (3×200 ml). The aqueous layer was cooled to 0° C. (ice bath) and neutralized using NaOH (24 g). The resulting slurry was extracted with diethyl ether (6×300 ml), dried using sodium sulfate and the diethyl ether was removed using a rotary evaporator to yield chloro-imidazo[1,2-b]pyridazine (10-1) as a light orange solid. MS: 155.1 [M+1]+.

1. customChloro-imidazo[1,2-b]pyridazine (10-1) was synthesized
2. temperaturethe reaction mixture was heated
3. temperatureto reflux
4. concentrationThe resulting dark brown reaction mixture was then concentrated under vacuum
5. filtrationThis solution was filtered through a celite pad
6. washthe solid washed with DCM
7. customthe solvent was then removed
8. customto yield a dark brown oil
9. stirringthe resulting slurry was stirred at room temperature for 15 minutes
10. filtrationThe solution was filtered through a celite pad
11. washthe filter cake was washed with water
12. extractionThe filtrate was extracted with diethyl ether (3×200 ml)
13. extractionThe resulting slurry was extracted with diethyl ether (6×300 ml)
14. customdried
15. customthe diethyl ether was removed
16. customa rotary evaporator

ORD-Eintrag

ord-f8bf7fc269894a45afa052e54350ed10

Quelldatensatz

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08507488B2