Acetone → 4-(4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazol-2-yl)cyclohexanone

HRID 1930060ノート

反応式

HRID 1930060 の反応式
Br[CH:2]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[F:12])=O.O1[C:29]2([CH2:34][CH2:33][CH:32]([C:35](=[S:37])[NH2:36])[CH2:31][CH2:30]2)[O:28]CC1.CC(C)=O.Cl>CN(C=O)C>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:36]=[C:35]([CH:32]2[CH2:33][CH2:34][C:29](=[O:28])[CH2:30][CH2:31]2)[S:37][C:2]=1[C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1

参加物

6

反応物 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanoneHCID 579299251,4-Dioxaspiro[4.5]decane-8-carbothioamide

生成物 1

HCID 579298484-(4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazol-2-yl)cyclohexanone収率 69.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

The 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.622 g, 1.57 mmol, Preparation #A.2) and 1,4-dioxaspiro[4.5]decane-8-carbothioamide (0.317 g, 1.57 mmol) were dissolved in DMF (5 mL) then stirred at ambient temperature for about 12 h. The mixture was concentrated under reduced pressure then acetone (25 mL) and concentrated hydrochloric acid (2 μL, 10 mmol) were added. The mixture was heated to about 60° C. for about 1.5 h then concentrated under reduced pressure, basified with 50% NaOH and diluted with water. The mixture was extracted with ethyl acetate then organic solution was dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified by flash chromatography on silica gel using DCM/MeOH (95:5) as an eluent to give the title compound (0.495 g, 69%): LC/MS (Table 1, Method b) Rt=2.14 min; MS m/z: 454.2 (M+H)+.

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. temperatureThe mixture was heated to about 60° C. for about 1.5 h
  3. concentrationthen concentrated under reduced pressure
  4. additiondiluted with water
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialorganic solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe material was purified by flash chromatography on silica gel

出典と根拠

ORDレコード
ord-b55b774aeb904736b2fae18b64e78a13
出典データセット
uspto-grants-2012_05
特許番号
US08188083B2

反応ノート

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