(R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-nitroimidazo[1,2-b]pyridazine → (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine

Temperature

70 °C

To a mixture of (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-nitroimidazo[1,2-b]pyridazine (4.17 g, 12.1 mmol) and SnCl2 dihydrate (10.9 g, 48.4 mmol) in a flask was added 200 mL EtOH to form a suspension. The reaction was heated at 70° C. for 1 hour to reach completion. After cooling to ambient temperature, the reaction mixture was concentrated. Water (200 mL) was added to the resulting crude solid residue, and the mixture was briefly sonicated and then vacuum-filtered. The filtrate pH was neutralized with 6N NaOH solution and extracted with DCM (3×250 mL). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, and concentrated to yield the crude product as a yellowish foamy solid. The crude material was purified by C-18 reverse-phase column chromatography (eluent=5 to 60% acetonitrile/water) to provide the pure product as a light yellowish powder (3 g, 78% yield).

1. customto form a suspension
2. temperatureAfter cooling to ambient temperature
3. concentrationthe reaction mixture was concentrated
4. additionWater (200 mL) was added to the resulting crude solid residue
5. customthe mixture was briefly sonicated
6. filtrationvacuum-filtered
7. extractionextracted with DCM (3×250 mL)
8. washThe combined organic layers were washed with brine (200 mL)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customto yield the crude product as a yellowish foamy solid
12. customThe crude material was purified by C-18 reverse-phase column chromatography (eluent=5 to 60% acetonitrile/water)

ORD record

ord-08b536dea41b4a719a9f9d9fb7f527aa

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227975B2