反应详情

温度

140 °C

A mixture of (2-bromo-3-methylphenyl)(pyrrolidin-1-yl)methanone (0.115 g, 0.429 mmol), (R)—N-(4-methoxybenzyl)-3-(3-methylmorpholino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.07 g, 0.143 mmol), potassium phosphate, anhydrous (0.121 g, 0.572 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.014 g, 0.029 mmol), and Pd2(dba)3 (0.013 g, 0.014 mmol) was purged with N2 followed by the addition of degassed dioxane (1 mL) and degassed water (0.5 mL). The resulting mixture was heated in microwave at 140° C. for 12 min. The reaction went to completion and it was filtered, concentrated, and chromatographed on silica gel using 0-5% MeOH/DCM to afford a yellow oil. To the product was added TFA (10 mL, 130 mmol) and the solution was heated at 60° C. for 18 h until the starting material was consumed. The mixture was concentrated and chromatographed on silica gel using 0-5% 2 M NH3 in MeOH/DCM to afford a yellow solid as (R)-(2-(2-amino-3-(3-methylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone. MS (ESI, pos. ion) m/z: 431 (M+1).

1. customwas purged with N2
2. additionfollowed by the addition of degassed dioxane (1 mL)
3. customdegassed water (0.5 mL)
4. filtrationwas filtered
5. concentrationconcentrated
6. customchromatographed on silica gel using 0-5% MeOH/DCM
7. customto afford a yellow oil
8. temperaturethe solution was heated at 60° C. for 18 h until the starting material
9. customwas consumed
10. concentrationThe mixture was concentrated
11. customchromatographed on silica gel using 0-5% 2 M NH3 in MeOH/DCM