O[C:2]1[N:11]=C(O)[C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:8]=2)[N:3]=1.O=P(Cl)(Cl)Cl.P(Cl)(Cl)(Cl)(Cl)[Cl:23].C([O-])(O)=O.[Na+].[CH2:33]([Cl:35])Cl>O>[Cl:23][C:2]1[N:11]=[C:33]([Cl:35])[C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:8]=2)[N:3]=1
To a 250 mL flask charged with methyl 2,4-dihydroxyquinazoline-7-carboxylate was added POCl3 (76 mL), PCl5 (12.1 g, 58.1 mmol), and the suspension heated at reflux overnight under nitrogen. In morning a dark orange solution has formed. The POCl3 was removed and the residue azeotroped with toluene to yield an orange solid that was taken into DCM (50 mL) and added slowly to stirred satd NaHCO3 (300 mL). The bi-phasic solution was then diluted with DCM (100 mL) and water (30 mL) and stirred for 1 hour at room temp. DCM (500 mL) was added and the mix transferred to a sep-funnel. The DCM layer was removed along with a large amount of ppt. The aq. was extracted with DCM (3×100 mL) and the combined organics dried over MgSO4, filtered and stripped to a orange solid that was purified by Biotage 65 flash chromatography eluting with DCM −3% MeOH/DCM over 3.5 L to reveal the title compound as a white solid, 4.4 g, 59%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.47 (1H, d, J=1.01 Hz) 8.43 (1H, d, J=8.84 Hz) 8.29 (1H, dd, J=8.72, 1.64 Hz) 3.96 (3H, s); MS (API+) for C10H6N2Cl2O2 m/z 257.0 (M+H)+.
불러오는 중…
