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

HRID 456154Notes

Reaction equation

HRID 456154 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 4 mL AcOH was heated at 110° C. for 7 hours. 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 which contains some iodine and used in the next step without further purification (180.0 mg, 44%, 36% pure). 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-e61672b0b85f4a8794f74fb09d1540d9
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

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