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

反応式

HRID 69233 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-04d708a7cb954f2f87e04b335ac02dde
出典データセット
uspto-grants-2014_09
特許番号
US08822468B2

関連ノート

読み込み中…