Sodium Thiosulfate → 2-(4-Fluorophenyl)-3-iodo-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine

HRID 80707Notes

Reaction equation

HRID 80707 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[N:12][N:11]3[CH:23]=2)=[CH:4][CH:3]=1.[I:24]Cl.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]4)=[N:12][N:11]3[C:23]=2[I:24])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 24640Iodine chlorideHCID 516892Sodium BicarbonateHCID 594069602-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 594069722-(4-Fluorophenyl)-3-iodo-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazineYield 91.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution, cooled to about 5° C., of 31.0 g (99.6 mmol) of 2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine in chloroform is rapidly added dropwise a solution of 64.7 g (398 mmol) of iodine monochloride in 150 mL of methanol. Mild exothermicity and the formation of a precipitate during the addition are observed. After cooling to room temperature and stirring for 30 minutes, the mixture is poured into 2 L of aqueous 5% sodium thiosulfate solution saturated with sodium bicarbonate. After vigorous stirring until the mixture has decolorized, the product is extracted with chloroform. The organic phase is separated out, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a brown solid. This solid is triturated in a mixture of 400 mL of diisopropyl ether and 50 mL of isopropanol at reflux. After cooling, 40 g of a beige-colored powder are isolated by filtration through a sinter funnel and drying under vacuum.

Workup

  1. additionMild exothermicity and the formation of a precipitate during the addition
  2. stirringAfter vigorous stirring until the mixture
  3. extractionthe product is extracted with chloroform
  4. customThe organic phase is separated out
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a brown solid
  9. customThis solid is triturated in a mixture of 400 mL of diisopropyl ether and 50 mL of isopropanol
  10. temperatureat reflux
  11. temperatureAfter cooling

Sources & evidence

ORD record
ord-f874c6a4b9a3473289485f5fc94d0801
Source dataset
uspto-grants-2014_09
Patent number
US08846676B2

Reaction notes

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