Pentafluoroiodobenzene → N-Cyclopropylmethyl-2-ethyl-7-iodo-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrazolo[1,5-a]pyridine-3-amine

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A solution of N-cyclopropylmethyl-N-(2-ethylpyrazolo[1,5-a]pyridine-3-yl)-N-(tetrahydro-2H-4-pyranylmethyl)amine (180 g, 574 mmol) in tetrahydrofuran (1620 mL) was cooled in a dry ice-ethanol bath. Into the reaction mixture was dropped n-butyllithium (1.6M hexane solution; 538 mL, 854 mmol) at an inner temperature of −73° C. to −64.5° C. At the same temperature, the reaction mixture was stirred for 1 hour, and into the reaction mixture was dropped pentafluoroiodobenzene (115 mL, 861 mmol). The reaction mixture was further stirred for 1 hour and 20 minutes at the same temperature, and to the reaction mixture was added water/tetrahydrofuran (1/1, v/v, 360 mL). Into the reaction mixture was added water (3600 mL) and heptane (3600 mL). An aqueous layer was removed, and an organic layer was washed with water (3600 mL). Then, to the organic layer was added 5N hydrochloric acid (1800 mL) and the aqueous layer was separated. Then, the aqueous layer was cooled in an ice water bath, and a 5N sodium hydroxide aqueous solution (1620 mL) was added, then, toluene (3600 mL) was added, and an organic layer was separated. The remaining aqueous layer was further extracted with toluene (3600 mL), and both the organic layers were combined. The solution was concentrated under reduced pressure, to obtain 220 g of a title compound as deep green oil (yield: 87.3%).

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