Ammonia → 4-Chloro-6-fluoropyrrolo[1,2-b]pyridazine-3-carboxamide

Temperature

120 °C

To a slurry of 6-fluoro-4-hydroxypyrrolo[1,2-b]pyridazine-3-carboxylic acid (0.400 g, 2.039 mmol) in POCl3 (15.64 g, 102 mmol) was added diisopropylethylamine (0.39 mL, 2.24 mmol) and the resulting mixture was heated at 120° C. for 3 h with stirring. The reaction was cooled to rt and concentrated to remove the excess POCl3 and the resulting residue was dissolved in dichloromethane (15 mL) and reconcentrated and the process was repeated 2 more times to afford a brown oil. This material was dissolved in dichloromethane (10 mL) and the solution was added dropwise via pipette into a 0° C. well stirred solution of ammonia in dichloromethane (˜100 mL, prepared by extracting 100 mL of conc. Aq ammonium hydroxide with 3×30 mL portions of dichloromethane). After the addition was complete, the mixture was concentrated under vacuum and water was added to give a slurry which was filtered to collect the precipitated solid. The solid was rinsed with additional water and dried to afford 355 mg (81%) of the title compound as a yellow solid. HPLC (condition B): retention time=2.05 min. LCMS (condition B): m/z 197 +ve.

1. temperatureThe reaction was cooled to rt
2. concentrationconcentrated
3. customto remove the excess POCl3
4. dissolutionthe resulting residue was dissolved in dichloromethane (15 mL)
5. customto afford a brown oil
6. additionAfter the addition
7. concentrationthe mixture was concentrated under vacuum and water
8. additionwas added
9. customto give a slurry which
10. filtrationwas filtered
11. customto collect the precipitated solid
12. washThe solid was rinsed with additional water
13. customdried

ORD record

ord-27c6e7323a4240209cf4b7d37b4aad24

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221826B2