反应详情

温度

100 °C

A 100 mL round-bottomed flask was charged with 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (100 mg, 0.204 mmol, prepared in Example 7, step B), tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (217 mg, 1.02 mmol), copper(I)iodide (15.5 mg, 0.0816 mmol), (S)-pyrrolidine-2-carboxylic acid (18.8 mg, 0.163 mmol), K2CO3 (141 mg, 1.02 mmol) and DMSO (10 mL). The reaction mixture was stirred at 100° C. overnight. The reaction was cooled to ambient temperature and partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford the desired product (44.8 mg, 38.2%). LRMS (APCI pos): m/e 575 (M+1).

1. temperatureThe reaction was cooled to ambient temperature
2. custompartitioned between EtOAc and H2O
3. customThe phases were separated
4. extractionthe aqueous phase was re-extracted with EtOAc
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1