Carbon Tetrachloride → 7-Chloro-2,3-bis[2-(methylsulfanyl)pyrimidin-4-yl]pyrazolo[1,5-a]pyridine

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Reaction Steps

To a −78° C. solution of 2,3-bis[2-(methylsulfanyl)pyrimidin-4-yl]pyrazolo[1,5-a]pyridine (0.72 g, 2.0 mmol) in tetrahydrofuran (50 mL) was added a 2 M solution of lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (2.9 mL, 5.9 mmol) dropwise. The reaction mixture was stirred for 15 minutes, then carbon tetrachloride (5 mL) was added. The reaction mixture was stirred for 1 hour and quenched with brine and extracted with ethyl acetate (3×25 mL). The organic phase was washed with brine (3×25 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (1:9 acetone:dichloromethane) to give 260 mg (32%) of 7-chloro-2,3-bis[2-(methylsulfanyl)pyrimidin-4-yl]pyrazolo[1,5-a]pyridine. 7-Chloro-2,3-bis[2-(methylsulfanyl)pyrimidin-4-yl]pyrazolo[1,5-a]pyridine (0.098 g, 0.24 mmol) was dissolved in dichlormethane (3 mL) and cooled to 0° C. To the solution was added 3-chloroperoxybenzoic acid (0.13 g, 0.73 mmol). The reaction mixture was allowed to warm to room temperature and stirred overnight The mixture was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate, and concentrated under reduced pressure. To 7-chloro-2,3-bis[2-(methylsulfinyl)pyrimidin-4-yl]pyrazolo[1,5-a]pyridine (0.027 g, 0.062 mmol) was added 2-methoxyethylamine (2 mL) and the reaction was heated to 100° C. in a sealed tube overnight. The reaction mixture was cooled to room temperature and concentrated by evaporation under reduced pressure. The residue was purified by silica gel chromatography eluting with 1:1 acetone:dichloromethane to give 15 mg (49%) of N-(2-methoxyethyl)-2,3-bis{2-[(2-methoxyethyl)amino]pyrimidin-4-yl}pyrazolo[1,5-a]pyridin-7-amine. 1H NMR (CDCl3): δ 8.41 (d, 1H), 8.16 (d, 1H), 7.69 (d, 1H), 7.36 (d, 1H), 7.05 (m, 1H), 6.65 (d, 1H), 6.33 (t, 1H), 6.09 (d, 1H), 5.57 (m, 1H), 5.42 (t, 1H), 3.37–3.80 (m, 21H); MS m/z 494 (M+1).

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