6-Bromoindazole

2-Fluoro-4-bromobenzaldehyde (20.0 g, 98.5 mmol) was suspended in hydrazine hydrate (100 mL) and heated under reflux for 20 hours. Cooling to room temperature to produce a large number of precipitates, The precipitate was collected by filtration and washed with water, and dried to give the title compound (17.3 g, 89.1percent).A solution of 2-fluoro-4-bromobenzaldehyde (5.09g, 25 mmol) was dissolved in glyme (25 mE) and slowlytreated over 10 minutes with anhydrous hydrazine (25 mE, 0.8 mol, 32 eq.).11274] The resulting biphasic mixture was then held at reflux overnight. The reflux condenser was replaced with a short-path distillation head and about half the solvent distilled, at which time the reaction flask showed one phase and two phases were evident in the distillate. The undistilled residue was cooled and treated with water (25 mE), forming a white precipitate. This solid was collected by filtration, washed thoroughly with water, and dried in vacuo to give 6-bromoindazole (4.21 g, 85percent) as white crystals.To a 100 mL round-bottomed flask was added hydrazine (30 mL, 832 mmol) and 4-bromo-2-fluorobenzaldehyde (4.69 g, 23 mmol). The solution was stirred at 125° C. for 3 hours. After cooling to ambient temperature, the solution was concentrated under reduced pressure. The solution was quenched by pouring it into a mixture of ice water (100 mL), and then extracting with EtOAc (3.x.100 mL). The organic layers were combined, dried over sodium sulfate, and filtered. The solution was evaporated to dryness, and adsorbed onto silica gel. The crude product was purified using column chromatography through a Redi-Sep.(R). pre-packed silica gel column (40 g), eluting with a gradient of 0percent to 100percent EtOAc in hexanes, to provide 6-bromo-1H-indazole (4.6 g, 18 mmol, 76percent yield). LCMS (M+H) 197.9 calc. for CTo a vigorously stirred solution of 5-bromo-2-fluorobenzaldehyde (40.6 g, 0.2 mol) in DMSO (80 mL) was added N6-Aminoindazole (1.33 g, 10 mmol) was dissolved in 48percent hydrobromic acid (5 mL) and water (16 mL). To the resulting solution at 0° C. was added dropwise a solution of sodium nitrite (0.77 g, 11 mmol) in water (9 mL). The mixture was stirred at 0° C. for 15 min. Urea (0.40 g) was added to remove excess nitrous acid. After stirring for 10 min, this solution was added dropwise to a stirred mixture of copper(I) bromide (4.3 g, 30 mmol), 48percent hydrobromic acid (10 mL) and water (24 mL) at room temperature. The reaction mixture was heated at 75-80° C. for 1.5 h, cooled to room temperature, basified with concentrated ammonium hydroxide, and extracted with chloroform (4.x.30 mL). The combined extracts were dried over sodium sulfate and concentrated to provide the bromoindazole (0.96 g, 48percent) as a greenish yellow solid; (i)

Molecular Weight:197.03
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:195.96361
Monoisotopic Mass:195.96361
Topological Polar Surface Area:28.7
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes