6-Iodo-1H-indazole

A concentrated hydrochloric acid (35 mL, 420 mmol) and an aqueous solution (30 mL) of sodium nitrite (6.64g, 96 mmol) were added to a suspension prepared by adding water (30 mL) to 6-aminoindazole (10.4 g, 78 mmol) at0°C and stirred at 0°C for 30 minutes. Subsequently, to this solution, an aqueous solution (30 mL) of potassium iodide(15.91 g, 96 mmol) was added at 0°C, stirred at room temperature for 30 minutes, to which dichloromethane (80 mL)was then added, and stirred at 40°C for 2 hours. The reaction mixture was cooled down to 0°C, then adjusted to pH =14 with a 3N sodium hydroxide aqueous solution, and the precipitate was taken by filtration. The resulting precipitatewas washed with 10percent sodium thiosulfate, dissolved in tetrahydrofuran, and then silica gel was added. After stirring atroom temperature for 1 hour, hexane (600 mL) was added and filtered. The residue was washed twice with a THF/hexane(1/3 (v/v)) solution, then the solvent was distilled away under a reduced pressure to obtain the title compound (15.23 g, 80percent) as an orange powder.1H NMR (400 MHz, CDCl3) δ 10.24 (1H, br, s), 8.04 (1H, br s), 7.92 (1H, br s), 7.51 (1H, br d, J = 8.4 Hz), 7.46 (1H, dd, J = 8.4, 1.2 Hz).(i) 6-Aminoindazole (1.0 g, 7.5 mmol) was mixed with ice (6 g) and water (3.5 mL). The reaction mixture was cooled to 0°C and concentrated aqueous hydrochloride solution (3.8 mL) was added followed by a solution of sodium nitrite (0.6 g, 8.2 mmol) in water (2.5 mL). After 10 min of stirring at 0°C potassium iodide (1.3 g, 9.0 mmol) was added in few portions. Then the cold bath was removed and reaction mixture was warmed to 40°C, heated for 40 min and next the temperature was increased to 50°C and heated for another 30 min. After cooled to ambient temperature the solution was alkalized with 10percent NaOH. The brown precipitate was collected by filtration and washed with saturated aqueous solution of sodium hydrogen carbonate. The crude product was dissolved in tetrahydrofuran (25 mL) and refluxed with silica gel for 10 min. To this slurry hexane was added and the mixture was vaccum filtered through a silica pad. The silica was washed with solution of tetrahydrofuran in hexane (2:3). The filtrate was concentrated under reduced pressure to give 6-iodoindazole (0.9 g). The 6-iodoindazole (0.9 g, 3.9 mmol) was dissolved in dry dichloromethane (30 mL), cooled to 0°C and N- bromosuccinimide (0.8 g, 4.3 mmol) was added in portions. The reaction mixture was stirred at 0°C for lh. The precipitate was collected by filtration and washed with dichloromethane. The obtained product 3-bromo-6-iodo-lH-indazole was used to the next step without further purification. LC-MS (m/z) 324.8 (M+l).To a solution of step-d product (12 g, 0.04 mol) in 1 , 4-dioxane (60 ml, 5 times), 6N HCI (60 ml, 5 times) was added at rt. Reaction mixture was heated to 7O

Molecular Weight:244.03
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:243.94975
Monoisotopic Mass:243.94975
Topological Polar Surface Area:28.7
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes