Iodine → 6-Chloro-3-[1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine

HRID 1959726Notes

Reaction equation

HRID 1959726 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[C:15]([F:25])=[C:16]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]([CH3:24])[N:18]=[CH:17]4)(O)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.II.[PH2](=O)O>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:14]3[C:15]([F:25])=[C:16]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]([CH3:24])[N:18]=[CH:17]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1

Participants

5

Reactant 3

HCID 807IodineHCID 4124402Phosphinic AcidHCID 581475291-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethanol

Product 1

HCID 581475396-Chloro-3-[1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazineYield 63.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethanol (530 mg, 1.457 mmol), Iodine (925 mg, 3.64 mmol) and phosphinic acid (50%, 0.556 mL) in 20 mL of acetic acid was heated at 110° C. for 2 h. Solvent was evaporated and the residue was dissolved in water, neutralized with saturated NaHCO3 solution and extracted with DCM three times. Organic layers were combined and washed with brine, dried over Na2SO4. Solvent was then evaporated and the crude was purified by flash chromatography (hexane:EtOAc=1:2) to give the title compound as light yellow solid (320 mg, 63.2%). 1H-NMR (400 MHz, MeOH-d4) δ ppm 8.03 (s, 1H), 8.0 (d, 1H), 7.8 (s, 1H), 7.23 (d, 1H), 7.19 (d, 1H), 5.1 (q, 1H), 4.0 (s, 3H), 1.92 (d, 3H). LCMS (method B): [MH]+=347.9, tR=2.69 min.

Workup

  1. customSolvent was evaporated
  2. dissolutionthe residue was dissolved in water
  3. extractionextracted with DCM three times
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customSolvent was then evaporated
  7. customthe crude was purified by flash chromatography (hexane:EtOAc=1:2)

Sources & evidence

ORD record
ord-d07e9828bf1f483486558722839534b5
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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