4-chloro-3-iodo-1H-pyrazolo[4,3-c]pyridine

A solution of 4-chloro-1H-pyrazolo[4, 3-c]pyridine (1.5 g, 9.77 mmol, 1.00 equiv), 1, 4-dioxane(25 mL), potassium hydroxide (2.0 g, 35.65 mmol, 3.60 equiv), and iodine (4.95 g, 19.50 mmol, 2.00 equiv) was stuffed for 4 h at 75 °C. The reaction was quenched by saturated aqueous sodium thiosulfate pentahydrate and the solids were collected by filtration. This resulted in 2.5 g (92percent) of the title compound as a light yellow solid. LC-MS (ES, mlz): 280 [M+H].To a solution of 4-chloro-lH-pyrazolo[4, 3-c]pyridine (5.5 g, 36 mmol) in DMF (50 mL) was added NIS (6.9 g, 69 mmol). The resulted mixture was stirred at 100 °C overnight. Then the mixture was cooled and diluted with water, the precipitate was collected by filtration and dried to to give 4-chloro-3-iodo-lH-pyrazolo[4, 3-c]pyridine (8.5 g, 85percent) as a light yellow solid.To a mixture of 4-chloro-1H-pyrazolo [4, 3-c] pyridine (5.8 g, 38 mmol, synthesized according to WO 2010106333A1 and WO 2012038743A1) and KOH (8 g, 142 mmol) in dioxane (100 mL) at room temperature was added iodine (19 g, 76 mmol) . The reaction mixture was stirred at 75 for 4 h and then allowed to cool to room temperature. The solution was diluted with saturated NaA solution of 4-chloro-1H-pyrazolo[4, 3-c]pyridine (102) (30 mg, 0.196 mmol) and NIS (66 mg 1.5 eq, 0.249mmol) in DMF (1 mL) was heated to 80 °C for 3 h. The mixture was concentrated in vacuo, brine (10 mL) was addedand then extracted with ethyl acetate (3 3 30 mL). The combined organic layer was washed with brine (10 mL), driedover MgSO4 and filtered. The filtrate was concentrated in vacuo to afford the desired product, 4-chloro-3-iodo-1Hpyrazolo[4, 3-c]pyridine (103) (34 mg, 62percent yield) as a white solid. ESI-MS m/z : 277.85 [M - H]- .The product obtainedwas used directly in the next step without purification.Intermediate 34-Chloro-3-iodo-1 H-pyrazolo[4, 3-c]pyridiTo a mixture of Intermediate 2 (5.8 g, 38 mmol) and KOH (8 g, 142 mmol) in dioxane (100 ml) at room temperature was added iodine (19 g, 76 mmol). The reaction mixture was stirred at 75 °C for 4 h, and then allowed to cool to room temperature. The solution was diluted with saturated NaIntermediate 12C) 4-chloro-3-iodo-1H-pyrazolo[4, 3-c]pyridine [1033] To a mixture of 4-chloro-1H-pyrazolo[4, 3-c]pyridine (4.0 g) and potassium hydroxide (4.4 g) in DME (50 mL) was added iodine (13.3 g) at room temperature. The reaction mixture was stirred at 75°C for 4 hr. The reaction mixture was added to aqueous sodium thiosulfate solution, and the mixture was left stand overnight, and the resulting solid was collected by filtration to give the title compound (6.3 g). MS(ESI+): [M+H]A solution of 4-chloro-lH-pyrazolo[4, 3-c]pyridine (750.0 mg, 4.902 mmol, 1.0 eq), KOH (988.0 mg, 17.647 mmol, 4.0 eq) and 12 (2.49 g, 9.804 mmoL, 2.0 eq) in 1, 4- dioxane (20.0 mL) was stirred at 75 °C for 4 h, then cooled and quenched by sat. aq. Na2S03 and the precipitate was collected by filtration to provide 4-chloro-3-iodo-lH- pyrazolo[4, 3-c]pyridine (1.57 g).

Molecular Weight:279.46
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:278.90602
Monoisotopic Mass:278.90602
Topological Polar Surface Area:41.6
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes