反应详情

To a solution of {1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid (0.515 g, 1.14 mmol) in NMP (8 ml), triethylamine (0.166 ml, 1.26 mmol) is added followed by HATU (0.452 g, 1.26 mmol). The mixture is stirred at RT for 5 minutes and then treated with 1-methylpiperazine (140.3 μL, 1.26 mmol). After 5 minutes at RT the reaction mixture is partitioned between EtOAc (25 ml) and water (25 ml). The phases are separated and the aqueous phase is washed further with EtOAc (2×20 ml). The organic extracts are combined, washed with saturated NaHCO3 (40 ml), brine (40 ml), dried (MgSO4), filtered and concentrated to give a brown oil. The residue is taken up in MeCN (5 ml) and passed through a 10 g Varian pre packed silica cartridge, eluting with MeCN then EtOAc to remove the impurities. The product is eluted off the column with MeOH. The MeOH fractions are combined and concentrated in vacuo and dried to afford the title compound, [M+H]+ 530.

1. customAfter 5 minutes at RT the reaction mixture is partitioned between EtOAc (25 ml) and water (25 ml)
2. customThe phases are separated
3. washthe aqueous phase is washed further with EtOAc (2×20 ml)
4. washwashed with saturated NaHCO3 (40 ml), brine (40 ml)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a brown oil
9. washeluting with MeCN
10. customEtOAc to remove the impurities
11. washThe product is eluted off the column with MeOH
12. concentrationconcentrated in vacuo
13. customdried