反应详情

To 2-(4-chloro-7-methyl-quinazolin-2-yl)-phenol (245 mg, 0.91 mmol) in 3.0 mL of CH2Cl2 was added 3-hydroxymethyl-piperazine-1-carboxylic acid benzyl ester (226 mg, 0.58 mmol) and triethylamine (190 μL, 1.37 mmol). The reaction mixture was stirred for 12 hours at room temperature, and additional 3-hydroxymethyl-piperazine-1-carboxylic acid benzyl ester (100 mg, 0.4 mmol) and triethylamine (200 μL, 1.4 mmol) was added, and the reaction mixture was heated at 40° C. for 6 h. The reaction mixture was cooled, and diluted with 5 mL of CH2Cl2 and 5 mL of water, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography eluting with 20-85% EtOAc/hexanes to give 3-hydroxymethyl-4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazine-1-carboxylic acid benzyl ester (216 mg, 65%). LCMS: m/z 485 (M+H)+ at 3.03 min (10%-99% CH3CN/H2O)

1. temperaturethe reaction mixture was heated at 40° C. for 6 h
2. temperatureThe reaction mixture was cooled
3. customthe organic layer was separated
4. dry with materialdried over Na2SO4
5. customThe solvent was removed under reduced pressure
6. customthe residue was purified by silica gel chromatography
7. washeluting with 20-85% EtOAc/hexanes