3-Bromo-6-chloroimidazo(1,2-b)pyridazine → (Rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-(3-methyl-3h-benzoimidazol-5-yl)-methanol

HRID 69233

Reaction equation

HRID 69233 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Mg]Br)C.[CH3:16][N:17]1[C:21]2[CH:22]=[C:23]([CH:26]=[O:27])[CH:24]=[CH:25][C:20]=2[N:19]=[CH:18]1>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:26]([C:23]3[CH:24]=[CH:25][C:20]4[N:19]=[CH:18][N:17]([CH3:16])[C:21]=4[CH:22]=3)[OH:27])=[CH:3][N:4]=2)[N:7]=1

Participants

5

Reactant 3

HCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 224649141-methyl-1H-benzo[d]imidazole-6-carbaldehydeHCID 178418443HCID 178418443, compound

Product 1

HCID 87524278(Rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-(3-methyl-3h-benzoimidazol-5-yl)-methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-Bromo-6-chloro-imidazo[1,2-b]pyridazine (850 mg, 3.47 mmol) was dissolved in THF (50 mL) under Argon. Ethylmagnesium bromide solution (1 M, 3.47 mL) was added and the mixture was stirred at rt for 20 min. Then 3-methyl-3H-benzoimidazole-5-carbaldehyde in THF (10 mL) was slowly added and the mixture was stirred at rt for 18 h. The mixture was quenched with water and NaHCO3. It was extracted with EtOAc twice and some MeOH to dissolve the solids. The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 25 min then up to 11% MeOH). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound as a pink foam (tR 1.79 min (conditions 8), MH+=314).

Workup

  1. stirringthe mixture was stirred at rt for 18 h
  2. customThe mixture was quenched with water and NaHCO3
  3. extractionIt was extracted with EtOAc twice
  4. dissolutionsome MeOH to dissolve the solids
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash chromatography (CombiFlash® Companion System®
  10. waitwith 40 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 25 min
  11. additionThe collected fractions containing product
  12. customwere evaporated
  13. customthe residue was dried under vacuum

Sources & evidence

ORD record
ord-04d708a7cb954f2f87e04b335ac02dde
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Linked notes

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