反应详情

A degassed solution of 2-bromo-1-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-3-methylbenzene (64.1 mg, 0.169 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (50 mg, 0.141 mmol, prepared as in Example 2, Step 1-2), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (13.42 mg, 0.028 mmol), potassium phosphate (149 mg, 0.704 mmol) and Pd2(dba)3 (6.44 mg, 7.04 μmol) in dioxane (0.94 mL)/water (0.47 mL) was heated in a sealed tube in the microwave at 140° C. for 15 min. The reaction was then quenched with water and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo to remove the solvent. The crude material was purified by column chromatography with 0-100% (10% NH3 in MeOH/DCM)/DCM to afford 6-(2-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine. MS (ESI, pos. ion) m/z: 528 (M+1).

1. customThe reaction was then quenched with water
2. extractionthe aqueous layer was extracted with EtOAc
3. washThe organic layer was then washed with water and brine (3× ea.)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customto remove the solvent
7. customThe crude material was purified by column chromatography with 0-100% (10% NH3 in MeOH/DCM)/DCM