Iodine → 6-Chloro-3-((1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine

HRID 1959663Notes

Reaction equation

HRID 1959663 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH3:22])[N:17]=[CH:16]4)O)=[CH:9][N:10]=2)[N:7]=1.II.O[PH2]=O>CC(O)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH3:22])[N:17]=[CH:16]4)=[CH:9][N:10]=2)[N:7]=1

Participants

5

Reactant 3

HCID 807IodineHCID 4124402Phosphinic AcidHCID 58190458(6-Chloroimidazo[1,2-b]pyridazin-3-yl)(1-methyl-1H-indazol-5-yl)methanol

Product 1

HCID 581905366-Chloro-3-((1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of (6-chloroimidazo[1,2-b]pyridazin-3-yl)(1-methyl-1H-indazol-5-yl)methanol (156.8 mg, 0.50 mmol), I2 (381 mg, 1.50 mmol) and H3PO2 (0.273 mL, 2.50 mmol) in AcOH (4 mL) was heated at 110° C. for 7 h. The solvent was removed under reduced pressure. The residue was diluted with water and extracted with DCM twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (DCM:MeOH=20:1) to give the title compound containing some iodine and used in the next step without further purification (180.0 mg, 36% purity, 44%). LCMS (method A): [MH]+=298, tR=5.37 min.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionThe residue was diluted with water
  3. extractionextracted with DCM twice
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-5037a9a3df9b40628538badf6b7228b2
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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