Hydrochloric Acid → 6-Butyl-2-chloroimidazo[1,2-b]pyridazine

HRID 969719

反応式

HRID 969719 の反応式
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[Cl-].C([Zn+])CCC.[Cl:12][C:13]1[N:14]=[C:15]2[CH:20]=[CH:19][C:18](Cl)=[N:17][N:16]2[CH:22]=1.Cl>O1CCCC1.[Cl-].[Zn+2].[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>[CH2:1]([C:18]1[CH:19]=[CH:20][C:15]2[N:16]([CH:22]=[C:13]([Cl:12])[N:14]=2)[N:17]=1)[CH2:2][CH2:3][CH3:4]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 144223582,6-Dichloroimidazo[1,2-b]pyridazineHCID 178418339ButyllithiumHCID 178448261HCID 178448261、化合物2 回

生成物 1

HCID 230280946-Butyl-2-chloroimidazo[1,2-b]pyridazine

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 178418745HCID 178418745、化合物触媒HCID 8028Tetrahydrofuran溶媒4 回

実験手順

Zinc chloride (2.04 g, 15.0 mmol) was dried at 180° C. for 2 hours under vacuum and then cooled to room temperature, and anhydrous tetrahydrofuran (20.0 mL) was added thereto. n-Butyl lithium (1.6 M, 9.0 mL, 14.4 mmol) was added dropwise thereto over about 30 minutes under ice-cooling and stirred for 30 minutes under ice-cooling, to prepare a solution of n-butylzinc chloride in tetrahydrofuran. Separately, a suspension of 2,6-dichloroimidazo[1,2-b]pyridazine (1.88 g, 10.0 mmol) and [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride (0.16 g, 0.30 mmol) in anhydrous tetrahydrofuran (20.0 mL) was prepared under a nitrogen atmosphere, and the previously prepared solution of n-butylzinc chloride in tetrahydrofuran was added dropwise thereto over 30 minutes with maintaining at 3 to 6° C. The mixture was stirred for 15 minutes under ice-cooling and for 3 hours at room temperature, poured into a saturated saline and adjusted to pH 2 with dilute hydrochloric acid. The reaction solution was extracted twice with ethyl acetate, and the extracts were combined, dehydrated over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to give the title compound as pale yellow crystals. The yield was 2.03 g (96.8%).

後処理

  1. temperatureover about 30 minutes under ice-cooling
  2. temperaturecooling
  3. customwas prepared under a nitrogen atmosphere
  4. temperatureover 30 minutes with maintaining at 3 to 6° C
  5. stirringThe mixture was stirred for 15 minutes under ice-
  6. temperaturecooling and for 3 hours at room temperature
  7. additionpoured into a saturated saline
  8. extractionThe reaction solution was extracted twice with ethyl acetate
  9. concentrationconcentrated under reduced pressure
  10. customThe residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:4)

出典と根拠

ORDレコード
ord-dafd2b571387437795ac686b100253b8
出典データセット
uspto-grants-2007_12
特許番号
US07307165B2

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