5-Bromo-3-iodo-1H-pyrazolo[3,4-b]pyridine

5-bromo-3 -iodo- 1 H-pyrazolo [3 , 4-bipyridine ( IV-A-I); To a stirred solution of the bromo-diazaindole III- A-I (1 g, 5.05 mmol) in DMF (14 mL) was added crushed KOH pellets (1.06 g, 19.03 mmol) in one portion. After 11 min, ITo a solution of 5-bromo-lH-pyrazolo[3, 4-b]pyridine (I) (5 g, 25.25 mmol, 1 eq) in 1, 4- dioxane (100 mL) and 4 N aqueous NaOH (100 mL) was added iodine (64.1 g, 252.5 mmol, 10 eq). The mixture was stirred at 60 °C overnight, and TLC showed the reaction was complete. The reaction mixture was extracted with EtOAc (100 ml x 2). The combined organic extracts were washed with saturated aqueous NaHS0[0116] To a solution of 5-bromo-1H-pyrazolo[3, 4-b]pyridine (I) (5 g, 25.25 mmol, 1 eq) in a mixture of 1 , 4-dioxane (100 mL) and 4 N aqueous NaOH (100 mL) was added iodine (64.1 g, 252.5 mmol, 10 eq). The resulting mixture was stirred at 60 °C overnight, and TLC showed the reaction was complete. The resulting mixture was extracted with EtOAc (100 ml x 2). The combined organic layers were washed with saturated aqueous NaHSO3 (100 mL x 3) and brine (50 mL), dried over Na2504, and concentrated to give the title compound 5-bromo-3-iodo-JH- pyrazolo[3, 4-b]pyridine (II) as an off-white solid (7.5 g , yield:91percent), which was used in the next step without any further purification.To a solution of 5-bromo-1H-pyrazolo[3, 4-b]pyridine (I) (5 g, 25.25 mmol, 1 eq) in 1, 4-dioxane (100 mL) and 4 N aqueous NaOH (100 mL) was added iodine (64.1 g, 252.5 mmol, 10 eq). The mixture was stirred at 60 °C overnight, and TLC showed the reaction was complete. The reaction mixture was extracted with EtOAc (100 ml x 2). The combined organics were washed with saturated aqueous NaHSO3 (100 mL x 3) and brine (50 mL), dried over Na2SO4, and concentrated to give the title compound 5-bromo-3-iodo-JH-pyrazolo[3, 4- b]pyridine (II) as an off-white solid (7.5 g , yield:91percent), which was used in the next step without any further purification.To a solution of 5-Bromo-1H-pyrazolo[3, 4-b]pyridine (2.0 g, 10.1 mmol) in DMF (20 mL) Potassium hydroxide (KOH, 1.2 g, 21.4 mmol) was added at 25 °C. The 5-bromo -1H-pyrazolo [3, 4-b] pyridine (2.0g, 10 . 1mmol) adding 20mLN, in N-dimethyl formamide, stirring to dissolve, then adding flaky potassium hydroxide (1.2g, 21 . 4mmol), stir at room temperature the reaction 10 minutes, and then added with the solid iodine (2.8g, 11 . 1mmol), stir at room temperature the reaction 4 experimental, then water (30 ml) dilution, ethyl acetate (3×20 ml) extraction, then with saturated sodium thiosulfate solution (2×30 ml) and saturated salt water (2×30 ml) washing, the organic phase is dried with anhydrous sodium sulfate, concentrated. Then the solid plus dioxane (30 ml) is dissolved, add potassium hydroxide (1.2g, 21 . 4mmol), stir to react under room temperature for 10 minutes, then adding solid iodine (2.8g, 11 . 1mmol), stir at room temperature reaction sleepovers, water reaction is ended (30 ml) dilution, ethyl acetate (3×20 ml) extraction, then with saturated sodium thiosulfate solution (2×30 ml) and saturated salt water (2×30 ml) washing, the organic phase is dried with anhydrous sodium sulfate, concentrated to obtain pale brown solid (2.8g, 85.6percent).Step 4: Synthesis of 5-bromo-3-iodo-lH-pyrazolo[3, 4-b]pyridine.[0220] 5-bromo-17J-pyrazolo[3, 4-b]pyridine (3.00 g, 15.2 mmol) and A'-iodosuccinimide(3.60 g, 16.0 mmol) were dissolved in anhydrous dichloroethane (100 mL). The resultingmixture was stirred under reflux conditions for 6 h, cooled to room temperature and dilutedwith THF (300 mL). The resulting solution was washed with a saturated aqueous solutionof sodium thiosulfate (100 mL) and brine, then dried over magnesium sulfate, filtered andconcentrated. The residue was titurated with a 1:1 mixture of dichloromethane and etherand then ether before being dried in vacuum to afford 5-bromo-3-iodo-l//-pyrazolo[3, 4-bjpyridine (3.795 g, 77percent yield) as a beige-brown solid. ^-NMR (500 MHz, 5-bromo-1H-pyrazolo[3, 4-b]pyridine (3.00 g, 15.2 mmol) and N-iodosuccinimide (3.60 g, 16.0 mmol) were dissolved in anhydrous dichloroethane (100 mL). The resulting mixture was stirred under reflux conditions for 6 h, cooled to room temperature and diluted with THF (300 mL). The resulting solution was washed with a saturated aqueous solution of sodium thiosulfate (100 mL) and brine, then dried over magnesium sulfate, filtered and concentrated. The residue was titurated with a 1:1 mixture of dichloromethane and ether and then ether before being dried in vacuum to afford 5-bromo-3-iodo-1H-pyrazolo[3, 4-b]pyridine (3.795 g, 77percent yield) as a beige-brown solid. N-Iodosuccinimide (8.1 g, 34.1 mmol) was added to a solution of 5- bromo-lH-pyrazolo[3, 4-b]pyridine (4.5 g, 22.7 mmol) in dichloroethane (100 mL), and the reaction mixture was heated to reflux overnight. The reaction mixture was cooled to room temperature and diluted with THF (300 mL). The organic layers were washed with saturated Na5-Bromo-1H-pyrazolo[3, 4-b]pyridine (19.7 g, 100 mmol) was dissolved in 150 mL of 1, 2-dichloroethane, and N-iodosuccinimide (24.8 g) was added. , 110 mmol), heated to reflux overnight.After the reaction was completed, the sodium thiosulfate solution was added and stirred for 20 min, and a yellow solid was charged and analyzed, and the mixture was filtered under reduced pressure. The filter cake was washed thoroughly with petroleum ether and dried in vacuo.A yellow solid was obtained 22.7 g (Yield: 70percent).Four grams of compound d and 10.25 g of iodine were dissolved into 50 ml N, N-dimethylformamide, stirred for 5 minutes at room temperature. Slowly, 2.83 g of potassium hydroxide was added into the above solution, and further stirred at room temperature for 3 hours, the reaction was completed. The reactant liquid was poured into 1000 ml water, solid was precipitated, filtered, the filter cake was washed three times by water immersion, vacuum dried to obtain compound e (m=1.35 g, yield: 41.3percent). (0183) Compound 4b (8 mg, 0.033 mmol), bromine (20 μL, 0.39 mmol) and acetic acid (1 mL) were added to a flask and the mixture was heated to reflux overnight. The reaction mixture was concentrated in vacuo, the residue was dissolved in EtOAc and sequentially washed with aqueous NaHCO

Molecular Weight:323.92
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:322.85551
Monoisotopic Mass:322.85551
Topological Polar Surface Area:41.6
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes