p-Toluenesulfonic acid → Methyl 4-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate

HRID 1755313Notes

Reaction equation

HRID 1755313 reaction equation
[NH2:1][C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[Br:18].Cl[CH2:20][CH:21](OCC)OCC.CC1C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[Br:18][C:3]1[C:2]2[N:7]([CH:20]=[CH:21][N:1]=2)[N:6]=[C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH:4]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 121282-Chloro-1,1-diethoxyethaneHCID 86682705Methyl 4-(6-amino-5-bromopyridazin-3-yl)benzoate

Product 1

HCID 86682706Methyl 4-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoateYield 36.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of methyl 4-(6-amino-5-bromopyridazin-3-yl)benzoate (1.64 g, 5.32 mmol), 2-chloro-1,1-diethoxyethane (0.984 g, 6.39 mmol) and PTSA (1.215 g, 6.39 mmol) in isopropanol (50 mL) was heated to 80° C. for 40 h. After cooling to room temperature, the solution was concentrated in vacuo. The resulting mixture was treated with a saturated NaHCO3 solution (50 mL), extracted with dichloromethane (50 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 methyl 4-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (640 mg, 36%) as a white solid. LC-MS: [M+H]+, 333.9, tR=1.637 min.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additionThe resulting mixture was treated with a saturated NaHCO3 solution (50 mL)
  3. extractionextracted with dichloromethane (50 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-adab5625d3314637a6929b3b18ce328b
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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