Methanethioamide → 4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazole

HRID 1930051ノート

反応式

HRID 1930051 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.[CH:25](=[S:27])[NH2:26]>C1COCC1>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:26]=[CH:25][S:27][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

4

反応物 2

HCID 3005587MethanethioamideHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

生成物 1

HCID 579299484-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thiazole収率 17.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.60 g, 1.5 mmol, Preparation #A.2) in THF (25 mL) was added methanethioamide (0.19 g, 3.0 mmol, prepared according to Euro. J. Med. Chem., 2004, 39, 867-872). The reaction mixture was stirred at ambient temperature for about 15 h. The solvent was removed under reduced pressure. The crude material was purified by silica gel flash chromatography using DCM/MeOH (gradient, 100:0 to 95:10). This residue was then repurified by silica gel flash chromatography using DCM/ACN (gradient, 90:10 to 0:100). The residue was dissolved in Et2O and solvent removed under reduced pressure to give a yellow solid. The solid was dried overnight under high vacuum to afford the title compound (0.095 g, 17%) as a yellow solid: LC/MS (Table 1, Method a) Rt=2.39 min; MS m/z: 358.2 (M+H.

後処理

  1. customThe solvent was removed under reduced pressure
  2. customThe crude material was purified by silica gel flash chromatography
  3. customThis residue was then repurified by silica gel flash chromatography
  4. dissolutionThe residue was dissolved in Et2O
  5. customsolvent removed under reduced pressure
  6. customto give a yellow solid
  7. customThe solid was dried overnight under high vacuum

出典と根拠

ORDレコード
ord-22bbaf0482254999bb89fc01c1049eee
出典データセット
uspto-grants-2012_05
特許番号
US08188083B2

反応ノート

読み込み中…