Dichloromethane → 6-(2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

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6-Chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (38.7 mg, 0.153 mmol), 2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-ylboronic acid (51.2 mg, 0.176 mmol), potassium carbonate (87.8 mg, 0.635 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (21.0 mg, 0.0257 mmol) were suspended in DME (1.0 mL) and water (0.30 mL). The flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.), stirred under nitrogen for 2 hours, and cooled to room temperature. In a separate flask, 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (933 mg, 3.69 mmol), 2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-ylboronic acid (1.338 g, 4.597 mmol), potassium carbonate (2.096 g, 1.517 μmol), and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (360.9 mg, 0.4419 mmol) were suspended in DME (15 mL) and water (4.0 mL). Nitrogen was bubbled through the suspension for about 30 seconds, and then the flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.) and stirred under nitrogen, After 1 hour and 45 minutes, the reaction was cooled to room temperature. At this point, both reactions were combined, and the aqueous phase was removed via pipette. Then, the combined reactions were filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated and treated with Et2O. No precipitate was observed, so this was concentrated and the residue was purified on a silica gel filter (about 3 inches, 50:1 DCM/2N ammonia in MeOH to 25:1 DCM/2N ammonia in MeOH to 10:1 DCM/2N ammonia in MeOH). Note: Product elutes with 50:1 DCM/2N ammonia. The fractions with product were collected, concentrated, and dried under high vacuum overnight to give 6-(2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (1.688 g, 69% purity, 68% yield). MS (ESI pos. ion) m/z 464 (M+H)+.

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