Chloroacetaldehyde → 8-Bromo-6-chloroimidazo(1,2-b)pyridazine

Temperature

50 °C

To a solution of 4-bromo-6-chloropyridazin-3-amine (6.0 g, 28.8 mmol) was added 2-chloroacetaldehyde (22.60 g, 144 mmol) (50% water solution). The reaction mixture was heated to 50° C. overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was diluted with CH2Cl2. Then, saturated NaHCO3 was added slowly until bubbling ceased. The layers were separated. The aqueous layer was extracted with CH2Cl2 (3×30 mL). The combined organic layer was washed with water and brine, dried over Na2SO4. The crude product was purified by BIOTAGE® (10-40% EtOAc/CH2Cl2, 2.1 L) to give 4.1 g (61%) product as a brown solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.01 (1H, s), 7.84 (1H, s), 7.39 (1H, s); 13C NMR (101 MHz, CDCl3) δ ppm 145.92 (1 C, s), 136.93 (1 C, s), 134.77 (1 C, s), 124.20 (1 C, s), 121.22 (1 C, s), 118.81 (1 C, s).

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationconcentrated
3. additionThe residue was diluted with CH2Cl2
4. additionThen, saturated NaHCO3 was added slowly
5. customuntil bubbling
6. customThe layers were separated
7. extractionThe aqueous layer was extracted with CH2Cl2 (3×30 mL)
8. washThe combined organic layer was washed with water and brine
9. dry with materialdried over Na2SO4
10. customThe crude product was purified by BIOTAGE® (10-40% EtOAc/CH2Cl2, 2.1 L)

ORD record

ord-49a1ee068b3a4e92a07af16347443ba4

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145419B2