Sulfuric Acid → 1-(2,4-Difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone
Reaction equation
[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]=1Participants
Conditions
- Temperature
- 90 °C
Procedure
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)+.
Workup
- custompartitioned with DCM (500 mL)
- customThe organic layer was isolated
- extractionthe aqueous layer was extracted with DCM (3×500 mL)
- dry with materialThe combined organic extracts were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give 19.5 g of crude material
- customThe crude material was purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-e2ad1809e78540068d601525cff2708b
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188083B2
Reaction notes
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