Sulfuric Acid → 1-(2,4-Difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone
반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]#[C:10][C:11]1[CH:12]=[CH:13][C:14]2[N:15]([C:17]([CH:20]([CH3:22])[CH3:21])=[N:18][N:19]=2)[N:16]=1.[OH:23]S(O)(=O)=O>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:23])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]2[N:15]([C:17]([CH:20]([CH3:22])[CH3:21])=[N:18][N:19]=2)[N:16]=1참가 물질
3
반응 조건
- 온도
- 90 °C
실험 절차
To a round bottom flask was added 6-((2,4-difluorophenyl)ethynyl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (19.5 g, 65.4 mmol, Preparation #J.1) and concentrated H2SO4 (145 mL, 1630 mmol). The reaction mixture was heated to about 90° C. for about 15 min. The reaction mixture was diluted with ice water (1000 mL) and partitioned with DCM (500 mL). The aqueous layer was neutralized with 50% aqueous NaOH (about 350 mL) to about pH 7. The organic layer was isolated and the aqueous layer was extracted with DCM (3×500 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to give 19.5 g of crude material. The crude material was purified by silica gel chromatography using EtOAc/acetone (gradient, 1:0 to 0:1) to give title compound (17.1 g, 83%) as a brown solid. LC/MS (Table 1, Method a) Rt=2.41 min; MS m/z: 317.2 (M+H)+.