N-bromobutanimide → (Rac)-3-[1-(3-bromo-imidazo[1,2-a]pyridin-6-yl)-ethyl]-6-m-tolyl-imidazo[1,2-b]pyridazine

HRID 69308Notes

Reaction equation

HRID 69308 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([CH:10]([C:12]3[N:16]4[N:17]=[C:18]([C:21]5[CH:22]=[C:23]([CH3:27])[CH:24]=[CH:25][CH:26]=5)[CH:19]=[CH:20][C:15]4=[N:14][CH:13]=3)[CH3:11])[CH:7]=[CH:6][C:5]=12.C1C(=O)N([Br:35])C(=O)C1>C(Cl)Cl>[Br:35][C:3]1[N:4]2[CH:9]=[C:8]([CH:10]([C:12]3[N:16]4[N:17]=[C:18]([C:21]5[CH:22]=[C:23]([CH3:27])[CH:24]=[CH:25][CH:26]=5)[CH:19]=[CH:20][C:15]4=[N:14][CH:13]=3)[CH3:11])[CH:7]=[CH:6][C:5]2=[N:1][CH:2]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 57917251HCID 57917251, compound

Product 1

HCID 57917261(Rac)-3-[1-(3-bromo-imidazo[1,2-a]pyridin-6-yl)-ethyl]-6-m-tolyl-imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(rac)-3-(1-Imidazo[1,2-a]pyridin-6-yl-ethyl)-6-m-tolyl-imidazo[1,2-b]pyridazine (Example 308, 100 mg, 0.283 mmol) was dissolved in DCM (2.8 mL) and NBS (50.4 mg, 0.283 mmol) was added. It was stirred at rt for 1 h then the solvent was removed. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM). Combined fractions were concentrated. The residue was repurified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and acetonitrile was removed. The aqueous solution was basified with 5% NaHCO3 solution and was extracted with EtOAc twice. Combined organic layers was washed with brine and dried over Na2SO4. It was filtered to afford the title compound after evaporation of the solvent as a white solid. (tR 1.0 min (conditions 2), MH+=432).

Workup

  1. customthe solvent was removed
  2. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM)
  3. concentrationCombined fractions were concentrated
  4. customThe residue was repurified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  5. customacetonitrile was removed
  6. extractionwas extracted with EtOAc twice
  7. washCombined organic layers was washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationIt was filtered

Sources & evidence

ORD record
ord-1366146d617343a2b654434fb85129e4
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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