Hydrochloric Acid → 2-Chloro-6-propylimidazo[1,2-b]pyridazine

HRID 969717

反応式

HRID 969717 の反応式
[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7](Cl)=[N:6][N:5]2[CH:11]=1.O1C[CH2:15][CH2:14][CH2:13]1.C([Mg]Br)CC.Cl>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH2:13][CH2:14][CH3:15])=[N:6][N:5]2[CH:11]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2 回HCID 144223582,6-Dichloroimidazo[1,2-b]pyridazineHCID 178455851HCID 178455851、化合物

生成物 1

HCID 230280952-Chloro-6-propylimidazo[1,2-b]pyridazine

試薬・触媒・溶媒 2

HCID 178418745HCID 178418745、化合物触媒HCID 962Water溶媒

実験手順

2,6-Dichloroimidazo[1,2-b]pyridazine (10.0 g, 53.2 mmol) and [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride (0.43 g, 0.80 mmol) were added to tetrahydrofuran (80.0 ml) under a nitrogen stream, and a solution of n-propylmagnesium bromide in tetrahydrofuran (2 M, 31.9 ml, 63.8 mmol) was added dropwise thereto under ice-cooling over 60 minutes. The reaction mixture was stirred for 10 minutes under ice-cooling, warmed to room temperature, and stirred for 2 hours at room temperature. To the reaction mixture was added cold water (700 ml), and acidified with concentrated hydrochloric acid. Then the deposited solid was collected by filtration, and insoluble solid was washed with dilute hydrochloric acid, then with water. At the same time, the filtrate was extracted with ethyl acetate, the extracts were combined, and washed with dilute hydrochloric acid, saturated brine, saturated sodium hydrogen carbonate solution, and saturated brine, in that order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The concentrated residue and the solid collected by filtration were purified by silica gel column chromatography (ethyl acetate:hexane=3:7) to give the title compound as white crystals. The yield was 9.21 g (88.5%).

後処理

  1. temperatureunder ice-cooling over 60 minutes
  2. temperaturecooling
  3. stirringstirred for 2 hours at room temperature
  4. filtrationThen the deposited solid was collected by filtration, and insoluble solid
  5. washwas washed with dilute hydrochloric acid
  6. extractionAt the same time, the filtrate was extracted with ethyl acetate
  7. washwashed with dilute hydrochloric acid, saturated brine, saturated sodium hydrogen carbonate solution, and saturated brine, in that order
  8. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. filtrationThe concentrated residue and the solid collected by filtration
  12. customwere purified by silica gel column chromatography (ethyl acetate:hexane=3:7)

出典と根拠

ORDレコード
ord-21d3bda608e84dd1bb1835b63083c486
出典データセット
uspto-grants-2007_12
特許番号
US07307165B2

関連ノート

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