Chlorosuccinimide → 3,6-Dichloroimidazo[1,2-b]pyridazine

HRID 1162090Notes

Reaction equation

HRID 1162090 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[Cl:11]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[Cl:11][C:8]1[N:6]2[N:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 138828Imidazo(1,2-b)pyridazine, 6-chloro-

Product 1

HCID 152710143,6-Dichloroimidazo[1,2-b]pyridazineYield 85.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

6-Chloroimidazo[1,2-b]pyridazine 41 (6.53 mmol) was dissolved in chloroform (12 mL) and N-chlorosuccinimide (6.53 mmol) added under N2. After stirring for 16 h, the mixture was partitioned between saturated sodium hydrogensulfate solution (25 mL) and chloroform (12 mL). The organic layer was removed, washed with water (2×), dried and concentrated to provide 3,6-dichloroimidazo[1,2-b]pyridazine 5 (1.05 g, 85%) as an orange solid; 1H NMR (500 MHz, CDCl3) δ 7.92 (d, J=9.5 Hz, 1H), 7.74 (s, 1H), 7.12 (d, J=9.5 Hz, 1H). 3,6-Dichloroimidazo[1,2-b]pyridazine 5 (150 mg, 0.8 mmol) and the desired amine (1 mL) were heated in a sealed tube for 16 hr at 120° C. Upon cooling the reaction mixture was concentrated and purified by column chromatography (12 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 80% methylene chloride over 30 min at 25 mL/min) to provide the desired product 6.

Workup

  1. customthe mixture was partitioned between saturated sodium hydrogensulfate solution (25 mL) and chloroform (12 mL)
  2. customThe organic layer was removed
  3. washwashed with water (2×)
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5f8f00c59d5b4fa4a11ef76a984833f1
Source dataset
uspto-grants-2010_10
Patent number
US07820670B2

Reaction notes

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