反应详情

温度

110 °C

A mixture of (3S*,5R*)-3-Amino-5-{cyclopropyl-[3-methoxy-5-(3-methoxy-propoxy)-benzyl]-carbamoyl}-piperidine-1-carboxylic acid tert-butyl ester (40 mg, 0.081 mmol), 3-bromotoluene (16 mg, 0.094 mmol), (rac)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (3.8 mg, 0.006 mmol), tris(dibenzylideneacetone)dipalladium(0) (3.8 mg, 0.004 mmol), and cesium carbonate (32 mg, 0.098 mmol) in toluene (0.6 mL) is heated at 110° C. for 36 h. The mixture is purified by RP-HPLC to give the desired amine, which is treated with 4 N HCl-1,4-dioxane (1 mL) at room temperature for 1 h. Concentration under vacuum gives the title compound as a white amorphous solid. MS: 481 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 3.07 min.

1. customThe mixture is purified by RP-HPLC