6-chloro-2-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide → 6-chloro-2-fluoro-3-(3-hydroxypropylsulfonamido)-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide

Participants

Reaction Steps

A 100 mL, round-bottomed flask was charged with 6-chloro-2-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy) propylsulfonamido)benzamide (30.0 mg, 0.053 mmol), Ce(NH4)2(NO2)6 (72.9 mg, 0.13 mmol) and CH3CN (0.5 mL) The reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (overnight). Then the reaction mixture was partitioned between EtOAc (200 mL) and water (100 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×100 mL) The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (EtOAc/hexane from 1/2 to 1/0, v/v) to afford impure 6-chloro-2-fluoro-3-(3-hydroxypropylsulfonamido)-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (20.3 mg). Further purification by preparation HPLC afforded pure product (2.1 mg, 8.6%). LRMS (APCI pos): >95% purity, 254 nm, m/e 458.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 8.59 (d, 1H), 8.50 (d, 1H), 7.65 (m, 1H), 7.36 (d, 1H), 4.01 (s, 3H), 3.65 (t, 2H), 3.25 (t, 2H), 2.03 (m, 2H).

Provenance & Evidence