反应详情

温度

80 °C

A suspension of 27.9 g (109 mMol) of 1-chloro-4-(4-pyridyl-methyl)-phthalazine (Example 67A.1 in WO 98/35958) and 21.4 g (109 mMol) of 5-amino-3chloro-benzotrifluoride (Example 5b) in 500 ml of ethanol and 27.4 ml of 4 N HCl/dioxane is stirred during 3 h a 80° C. After cooling down, the reaction mixture is diluted with 0.3 l of ether, filtrated, and washed with ether. The remaining solid is then taken up in water and EtOAc, brought to alkaline pH by means of NH3 solution, stirred for 15 min at room temperature and then filtered and washed with ether (→raw product). The water layer is removed from the filtrate and extracted twice with ethyl acetate. The organic layers are washed with water and brine, dried over Na2SO4 and evaporated. The residue is combined with the raw product mentioned above, and the solid is dissolved in ethyl acetate and methanol. About 100 g SiO2 are added, followed by evaporation, and the powder is applied onto a silica gel column and eluted with ethyl acetate and subsequently with a mixture of ethyl acetate and methanol (98:2→95:5, v/v). Solving the obtained fractions in ethyl acetate/methanol, partial evaporation and crystallization by addition of ether/hexane leads to the title compound: m.p. 231-232° C.; An. calc. (C21H14N4ClF3) C, 60.81%; H, 3.40%; N, 13.51; %; Cl, 8.55%; F, 13.74%; An meas. C, 60.8%; H, 3.4%; N, 13.5%; Cl, 8.5%; F, 13.8%; 1H-NMR (DMSO-d6) 9.63 (s, HN), 8.60 (d, 1H), 8.56 (s, 1H), 8.44 (d, 2H), 8.39 (s, 1H), 8.16 (d, 1H), 8.03 (t, 1H), 7.97 (t, 1H), 7.43 (s, 1H), 7.32 (d, 2H), 4.63 (s, 2H); FAB-MS (M+H)+=415.

1. temperatureAfter cooling down
2. filtrationfiltrated
3. washwashed with ether
4. stirringstirred for 15 min at room temperature
5. filtrationfiltered
6. washwashed with ether (→raw product)
7. customThe water layer is removed from the filtrate
8. extractionextracted twice with ethyl acetate
9. washThe organic layers are washed with water and brine
10. dry with materialdried over Na2SO4
11. customevaporated
12. dissolutionis dissolved in ethyl acetate
13. additionAbout 100 g SiO2 are added
14. customfollowed by evaporation
15. washeluted with ethyl acetate and subsequently with a mixture of ethyl acetate and methanol (98:2→95:5
16. custompartial evaporation and crystallization
17. additionby addition of ether/hexane leads to the title compound