3,6-Dichloro-4-isopropylpyridazine → HCID 59834510, compound

Temperature

100 °C

A mixture of 2,6-dibromo-4-(3-hydroxy-propyl)-phenol (20) (5.0 g, 16.3 mmol) in N,N-dimethyl acetamide (8 mL) was treated with potassium tert-butoxide (1.74 g, 15.48 mmol) under nitrogen at room temperature. The suspension was heated to 100° C. for 15 min and turned brown in color. 3,6-Dichloro-4-isopropyl pyridazine (7) (2.47 g, 12.9 mmol) was added to the suspension and the reaction was stirred at 140° C. for 24 h. The reaction was cooled to room temperature, diluted with water (180 mL) and extracted with ethyl acetate (3×100 mL). The organic layers were combined and were washed with a 1N aqueous sodium hydroxide solution (1×150 mL), followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried with sodium sulfate, filtered and concentrated. The resulting residue was purified by flash chromatography (Biotage 40M) eluted with 15% ethyl acetate in hexanes, followed by 25% ethyl acetate in hexanes, followed by 50% ethyl acetate in hexanes. The desired fractions were collected and concentrated under vacuum. The resulting solid was slurried in cold acetonitrile and filtered. The solid was then diluted with a 1:1 mixture of isopropyl acetate:methyl tert-butyl ether (20 mL). The mixture was heated to reflux and then cooled to room temperature. The solvent was decanted. The solid was slurried in heptane, filtered and dried under high vacuum overnight. The filtrate was concentrated. The resulting solid was then diluted with a 1:1 mixture of isopropyl acetate:methyl tert-butyl ether (20 mL). The mixture was heated to reflux and then cooled to room temperature. The solvent was decanted and the solid was slurried in heptane and filtered to afford a second crop of solid which was dried under high vacuum overnight. The solids were combined to afford 3-[3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-propan-1-ol (21) (1.48 g, 20%) as a white solid; LRMS for C16H17Br2ClN2O2 (M+H) m/z=465. Molecular Weight=464.5871; Exact Mass=461.9345

1. temperatureThe reaction was cooled to room temperature
2. extractionextracted with ethyl acetate (3×100 mL)
3. washwere washed with a 1N aqueous sodium hydroxide solution (1×150 mL)
4. dry with materialThe organic layer was dried with sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe resulting residue was purified by flash chromatography (Biotage 40M)
8. washeluted with 15% ethyl acetate in hexanes
9. customThe desired fractions were collected
10. concentrationconcentrated under vacuum
11. filtrationfiltered
12. additionThe solid was then diluted with a 1:1 mixture of isopropyl acetate
13. temperatureThe mixture was heated
14. temperatureto reflux
15. temperaturecooled to room temperature
16. customThe solvent was decanted
17. filtrationfiltered
18. customdried under high vacuum overnight
19. concentrationThe filtrate was concentrated
20. additionThe resulting solid was then diluted with a 1:1 mixture of isopropyl acetate
21. temperatureThe mixture was heated
22. temperatureto reflux
23. temperaturecooled to room temperature
24. customThe solvent was decanted
25. filtrationfiltered
26. customto afford a second crop of solid which
27. customwas dried under high vacuum overnight

ORD record

ord-8a5d8bc74edc4d02b612737805bc9835

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07452882B2