Acetic Anhydride → 7-Bromo-1H-pyrazolo[4,3-b]pyridine
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[C:3]=1[NH:9]C(=O)C.C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.[N:25](OCCC(C)C)=O>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:25][NH:9][C:3]=12Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 85 °C
Procedure
To a solution of N-(4-bromo-2-methylpyridin-3-yl)acetamide (0.6 g, 2.62 mmol) in toluene (26.2 ml) was added potassium acetate (0.308 g, 3.14 mmol) and acetic anhydride (0.743 ml, 7.86 mmol). The mixture was stirred for 15 minutes and isopentyl nitrite (0.806 ml, 6.02 mmol) was added and the reaction was heated at 85° C. for 4 hours. The reaction was cooled and partitioned between ethyl acetate (75 mL) and water (75 mL). The organic layer was separated, dried over MgSO4, and concentrated to a brown oil. The oil was purified on silica column chromatography eluted with methanol:dichloromethane (3:97). Concentration of product fractions afforded 7-bromo-1H-pyrazolo[4,3-b]pyridine (90 mg, 0.454 mmol, 17.35% yield) as an amber solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.71 (1H, d, J=4.80 Hz) 8.32-8.40 (1H, m) 8.40-8.51 (1H, m) 13.89 (1H, br. s.). MS [M+H] found 197.9.
Workup
- temperatureThe reaction was cooled
- custompartitioned between ethyl acetate (75 mL) and water (75 mL)
- customThe organic layer was separated
- dry with materialdried over MgSO4
- concentrationconcentrated to a brown oil
- customThe oil was purified on silica column chromatography
- washeluted with methanol:dichloromethane (3:97)
Sources & evidence
- ORD record
- ord-0500c04bce0d44c3bcc92583ce729d4d
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073918B2
Reaction notes
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