反应详情

温度

50 °C

A solution of crude 4-(4-fluoro-phenyl)-2-isopropyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (Example 164) in EtOH (1 L) was treated with citric acid (71 g, 0.37 mol). The solution was warmed to 50° C. to form a homogeneous solution, then was cooled to rt and stirred for 16 h. The mixture was diluted with Et2O (750 mL) and was stirred for 1 h. The precipitated white solid was collected by filtration and washed with cold EtOH (ca. 100 mL). The white solid was dried in a vacuum oven at 55° C. to give an off-white solid (157.3 g, 50% overall yield). HPLC: RT=6.86 min. MS (ESI): exact mass calcd. for C16H18FN3, 271.15; m/z found, 271.9 [M+H]+. 1H NMR (D2O): 7.49-7.43 (m, 2H), 7.27-7.19 (m, 2H), 4.28 (s, 2H), 3.60 (t, J=6.5, 2H), 3.20 (t, J=6.5, 2H), 3.11 (sept, J=6.9, 1H), 2.77 (d, J=15.4, 2H), 2.65 (d, J=15.4, 2H), 1.23 (d, J=6.9, 6H). 13C NMR (D2O): 176.59, 172.69, 171.99, 162.59 (d, JC-F=11.6), 160.67, 159.41, 129.42, 128.53 (d, JC-F=8.8), 115.91, 113.89 (d, JC-F=22.4), 71.78, 41,61, 40.10, 38.77, 34.78, 25.33, 18.64. The compounds in Examples 166-167 were prepared using methods analogous to those described in the preceding examples.

1. customto form a homogeneous solution
2. temperaturewas cooled to rt
3. stirringwas stirred for 1 h
4. filtrationThe precipitated white solid was collected by filtration
5. washwashed with cold EtOH (ca. 100 mL)
6. customThe white solid was dried in a vacuum oven at 55° C.
7. customto give
8. customan off-white solid (157.3 g, 50% overall yield)
9. customThe compounds in Examples 166-167 were prepared