反应详情

A 100 mL, round-bottomed flask was charged with 3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-amine (123.0 mg, 0.43 mmol), 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzoic acid (271.1 mg, 0.65 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (124.4 mg, 0.65 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (99.4 mg, 0.65 mmol), N-ethyl-N-isopropylpropan-2-amine (83.9 mg, 0.65 mmol) and DCM (1.5 mL). The reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (about 12 hours). Then the reaction mixture was partitioned between EtOAc (300 mL) and water (150 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×150 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 1/4 to 1/0, v/v) to afford 6-chloro-2-fluoro-N-(3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(3-(4-methoxyphenoxy)propylsulfonamido)benzamide (228.3 mg, 77.14%). LRMS (APCI pos): >95% purity, 254 nm, m/e 684.1 and 686.2 (M+1).

1. customhad been consumed (about 12 hours)
2. customThen the reaction mixture was partitioned between EtOAc (300 mL) and water (150 mL)
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with EtOAc (3×150 mL)
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto yield a crude product
9. customThe crude product was purified by silica gel chromatography (EtOAc/hexane from 1/4 to 1/0