反应详情

温度

180 °C

A microwave vial charged with 1-methylpiperazine (2.74 ml, 24.69 mmol) and 1-bromo-2-fluoro-4-(trifluoromethyl)benzene (2.000 g, 8.23 mmol) was heated to 180° C. in a microwave reactor for 90 minutes. The reaction mixture was concentrated then transferred to a vial charged with Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.291 g, 0.412 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (ASW Medchem, Brunswick, N.J., 2.96 g, 8.23 mmol), and potassium phosphate (8.74 g, 41.2 mmol). 8 mL dioxane and 4 mL water were added, and the reaction mixture was heated to 120° C. for 2 hours. After cooling to rt, the reaction mixture was poured into water and extracted with DCM. The organics were concentrated then purified by reverse phase column chromatography [RediSep Gold C18 150 g, 15 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielding tert-butyl 5-(2-(4-methylpiperazin-1-yl)-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.68 g, 3.53 mmol).

1. concentrationThe reaction mixture was concentrated
2. temperaturethe reaction mixture was heated to 120° C. for 2 hours
3. temperatureAfter cooling to rt
4. extractionextracted with DCM
5. concentrationThe organics were concentrated
6. customthen purified by reverse phase column chromatography [RediSep Gold C18 150 g, 15 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]