反应详情

A mixture of 3-(benzyloxy)-N-(3-(4-fluorophenyl)-2-oxopropyl)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.16 g, 0.3337 mmol) and POCl3 (2 mL) in toluene (15 mL) was heated at reflux for 5 h, then cooled, concentrated and the resulting residue taken up in EtOAc (50 mL), washed with water (2×10 mL), brine (10 mL), dried (Na2SO4), filtered and concentrated to give a yellow residue. Purification by preparative HPLC on C18 column using water/MeOH containing 0.1% TFA provided the title as a white solid which was crystallized from MeOH/H2O to afford colorless needles. 1HNMR (500 MHz, CDCl3) δ: 11.04-10.92 (1H, br s), 7.26 (2H, dd, J=8.6, 5.5 Hz), 7.04 (2H, t, J=8.6 Hz), 6.86 (1H, s), 4.10 (2H, s), 4.07-4.02 (4H, m), 1.65 (6H, s). HRMS (M+H) calcd for C19H19N3O4F: 372.1360. found: 372.1356. Anal calcd for C19H18N3O4F: C, 61.45; H, 4.88; N, 11.31. found: C, 61.19; H, 4.74; N, 11.14.

1. temperaturewas heated
2. temperatureat reflux for 5 h
3. temperaturecooled
4. concentrationconcentrated
5. washwashed with water (2×10 mL), brine (10 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give a yellow residue
10. customPurification by preparative HPLC on C18 column
11. customprovided the title as a white solid which
12. customwas crystallized from MeOH/H2O
13. customto afford colorless needles