Potassium Carbonate → 4-chloro-3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine

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Reaction Steps

To a solution of 4-chloro-3-iodo-1H-pyrazolo[3,4-b]pyridine (1.31 g, 4.688 mmol) in DMF (40 mL) was added K2CO3 (1.30 g, 9.38 mmol) and 1-(chloromethyl)-4-methoxybenzene (0.766 ml, 5.63 mmol). The reaction mixture was stirred at room temperature overnight to yield two regioisomeric products is a 5.5:1 ratio by LC-MS. The mixture was partitioned between EtOAc and H2O. The phases were separated and the organic layer washed with brine, dried over Na2SO4, filtered and concentrated to afford a dark yellow solid. The crude product was purified by flash column chromatography, eluting with 3:1 hexanes/EtOAc and loaded with 10:1:1 CH2Cl2/MeOH/THF due to poor solubility. The desired N1-regioisomeric product (1.256 g, 67%) was obtained as a white crystalline solid. LRMS (APCI pos) m/e 400, 402 (M+, Cl pattern). The undesired N2-regioisomer, 4-chloro-3-iodo-2-(4-methoxybenzyl)-2H-pyrazolo[3,4-b]pyridine, was not isolated.

Provenance & Evidence