HCID 131731819, compound → (Rac)-3-[1-(6-fluoro-1-methyl-1h-indazol-5-yl)-ethyl]-6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

HRID 69280Notes

Reaction equation

HRID 69280 reaction equation
ClC1C=CC2N(C(C(C3C=[C:15]4[C:19](=CC=3F)[N:18]([CH3:23])[N:17]=[CH:16]4)=O)=CN=2)N=1.Cl[C:25]1[CH:26]=[CH:27][C:28]2[N:29]([C:31]([C:34]([C:37]3[CH:38]=[C:39]4[C:43](=[CH:44][C:45]=3[F:46])[N:42]([CH3:47])[N:41]=[CH:40]4)(O)[CH3:35])=[CH:32][N:33]=2)[N:30]=1.C[Mg]Br>C1COCC1.CCOC(C)=O>[F:46][C:45]1[CH:44]=[C:43]2[C:39]([CH:40]=[N:41][N:42]2[CH3:47])=[CH:38][C:37]=1[CH:34]([C:31]1[N:29]2[N:30]=[C:25]([C:15]3[CH:16]=[N:17][N:18]([CH3:23])[CH:19]=3)[CH:26]=[CH:27][C:28]2=[N:33][CH:32]=1)[CH3:35]

Participants

5

Reactant 2

HCID 131731819HCID 131731819, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 57917432(Rac)-3-[1-(6-fluoro-1-methyl-1h-indazol-5-yl)-ethyl]-6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethanol (6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-(6-fluoro-1-methyl-1H-indazol-5-yl)-methanone (Stage 278.3, 3.7 g, 11.22 mmol) was dissolved in THF (250 mL) with heating under Argon. The solution was let to cool down and methylmagnesium bromide (3 M, 7.48 mL) was added. The mixture was stirred at rt for 1 h. It was then diluted with EtOAc and washed with a saturated NaHCO3 sol. The aqueous phase was extracted twice with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 20 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound (tR 1.14 min (conditions 2), MH+=346)

Workup

  1. temperaturewith heating under Argon
  2. temperatureto cool down
  3. washwashed with a saturated NaHCO3 sol. The aqueous phase
  4. extractionwas extracted twice with EtOAc
  5. washThe combined organics 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®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 20 min)
  10. additionThe collected fractions containing product
  11. customwere evaporated
  12. customthe residue was dried under vacuum

Sources & evidence

ORD record
ord-1b9959746a904c50a3dcd7cc5ce05d70
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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