Triethylamine → 3-(Azetidin-1-ylcarbonyl)-6-chloropyridazine

Temperature

0 °C

Phosphorus oxychloride (50 mL) was added to 6-hydroxypyridazine-3-carboxylic acid (9.82 g, 70.05 mmol) and the resulting solution heated to reflux. After 45 mins the solution was allowed to cool and the excess of phosphorus oxychloride was removed under reduced pressure. THF (50 mL) was added to the black residue and the resulting solution cooled to 0° C. Triethylamine (9.77 mL, 70.05 mmol) and azetidine (4.0 g, 70.05 mmol) were added dropwise. The resulting mixture was allowed to warm to RT and stirred overnight. The volatiles were removed under reduced pressure and water (50 mL) added, then the residue was adjusted to pH8 using sodium hydroxide solution. The aqueous layer was extracted five times with ethyl acetate, the combined organics dried (MgSO4) and the solvent removed to give the crude product as a dark oil. A sample was purified by preparative HPLC, eluting with 5-95% acetoniltrile in water (+0.2% TFA), and gave the title compound as a colorless solid (135 mg).

1. temperaturethe resulting solution heated to reflux
2. temperatureto cool
3. customthe excess of phosphorus oxychloride was removed under reduced pressure
4. additionTHF (50 mL) was added to the black residue
5. temperatureto warm to RT
6. customThe volatiles were removed under reduced pressure and water (50 mL)
7. additionadded
8. extractionThe aqueous layer was extracted five times with ethyl acetate
9. dry with materialthe combined organics dried (MgSO4)
10. customthe solvent removed
11. customto give the crude product as a dark oil
12. customA sample was purified by preparative HPLC
13. washeluting with 5-95%

ORD record

ord-fe7e5fa42b8b463489474ab286e25e8c

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977328B2