反应详情

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.

1. customto yield two regioisomeric products
2. customThe mixture was partitioned between EtOAc and H2O
3. customThe phases were separated
4. washthe organic layer washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto afford a dark yellow solid
9. customThe crude product was purified by flash column chromatography
10. washeluting with 3:1 hexanes/EtOAc