p-Toluenesulfonic acid → 8-Bromo-6-chloroimidazo(1,2-b)pyridazine

HRID 1755282Notes

Reaction equation

HRID 1755282 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[N:4][C:3]=1[NH2:9].Cl[CH2:11][CH:12](OCC)OCC.CC1C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[Br:1][C:2]1[C:3]2[N:4]([CH:11]=[CH:12][N:9]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 121282-Chloro-1,1-diethoxyethaneHCID 220244193-Amino-4-bromo-6-chloropyridazine

Product 1

HCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazineYield 98.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 4-bromo-6-chloropyridazin-3-amine (15.7 g, 75.3 mmol), 2-chloro-1,1-diethoxyethane (13.9 g, 90.3 mmol) and PTSA (17.2 g, 90.3 mmol) in isopropanol (150 mL) was heated to 80° C. for 20 h. After cooling to room temperature, the solution was concentrated in vacuo. The resulting mixture was treated with a saturated NaHCO3 solution (300 mL), extracted with dichloromethane (200 mL×3), dried over Na2SO4, filtered and concentrated. The residue was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give 8-bromo-6-chloroimidazo[1,2-b]pyridazine (17.2 g, 98%) as an orange solid. LC-MS: [M+H]+, 231.9, 233.9, tR=1.46 min.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additionThe resulting mixture was treated with a saturated NaHCO3 solution (300 mL)
  3. extractionextracted with dichloromethane (200 mL×3)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-516059dd23a84e1abfe4108efdc98a41
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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