Triethylamine hydrochloride → 6-Chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine

HRID 11226

反応式

HRID 11226 の反応式
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[CH:8]1[CH2:11][CH2:10][CH2:9]1.[C:13]([NH:21][NH2:22])(=O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.C(N(CC)CC)C>CC1C=CC(C)=CC=1>[Cl:1][C:2]1[C:7]([CH:8]2[CH2:11][CH2:10][CH2:9]2)=[CH:6][C:5]2[N:4]([C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:21][N:22]=2)[N:3]=1

参加物

5

反応物 3

HCID 11130Triethylamine hydrochlorideHCID 11955BenzoylhydrazineHCID 219732193,6-Dichloro-4-cyclobutylpyridazine

生成物 1

HCID 110005936-Chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine収率 34%

試薬・触媒・溶媒 1

HCID 7809P-Xylene溶媒

実験手順

A mixture of 3,6-dichloro-4-cyclobutylpyridazine from above (55.7 g, 0.27 mol), benzoic hydrazide (41.1 g, 0.30 mol) and triethylamine hydrochloride (41.5 g, 0.30 mol) in p-xylene (0.4 l) was stirred and heated at reflux under a stream of nitrogen for 24 hours. Upon cooling the volatiles were removed in vacuo. The residue was partitioned between dichloromethane and water. The aqueous was basified by the addition of solid potassium carbonate. Some dark insoluble material was removed by filtration at this stage. The aqueous phase was further extracted with dichloromethane (×2). The combined extracts were dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica gel eluting with 5%→10%→25% ethyl acetate/dichloromethane to give the title compound, (26.4 g, 34%) as an off-white solid. Data for the title compound: 1H NMR (360 MHz, CDCl3) δ 1.90–2.00 (1H, m), 2.12–2.28 (3H, m), 2.48–2.57 (2H, m), 3.69–3.78 (1H,m), 7.49–7.59 (3H, m), 7.97 (1H, s), 8.45–8.48 (2H, m); MS (ES+) m/e 285 [MH]+, 287 [MH]+.

後処理

  1. temperatureheated
  2. temperatureat reflux under a stream of nitrogen for 24 hours
  3. temperatureUpon cooling the volatiles
  4. customwere removed in vacuo
  5. customThe residue was partitioned between dichloromethane and water
  6. additionThe aqueous was basified by the addition of solid potassium carbonate
  7. customSome dark insoluble material was removed by filtration at this stage
  8. extractionThe aqueous phase was further extracted with dichloromethane (×2)
  9. dry with materialThe combined extracts were dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by chromatography on silica gel eluting with 5%→10%→25% ethyl acetate/dichloromethane

出典と根拠

ORDレコード
ord-26548357d3fb4ca6b89c4b2d9219dad3
出典データセット
uspto-grants-2006_08
特許番号
US07098208B2

関連ノート

読み込み中…