反应详情

温度

55 °C

Dissolve ethyl-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-amine (preparation 74, 110 mg, 0.47 mmol) in THF (6 mL), add triethylamine (95 mg, 0.94 mmol) and 2,4,6-trifluorobenzoyl chloride (136 mg, 0.70 mmol) sequentially, heat at 55° C. overnight. Quench the reaction with 0.1N NaOH, extract with methylene dichloride three times. Combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 3.5% 2M NH3-methanol in methylene dichloride provides 151 mg (82%) of the title compound as an oil: mass spectrum (ion spray): m/z=394.1 (M+1); 1H NMR (CDCl3, ppm): 7.43 (t, 1H), 6.52 (m, 4H), 4.82 (m, 1H), 4.03 (q, 2H), 2.73 (m, 2H), 2.33 (s, 3H), 2.26 (m, 2H), 1.95 (m, 2H), 1.75 (m, 2H), 1.31 (t, 3H). Mono-hydrochloride salt: Anal calcd for C20H22F3N3O2.HCl.H2O: C, 53.63; H, 5.63; N, 9.38. Found: C, 53.66; H, 5.12; N, 9.29.

1. customQuench
2. customthe reaction with 0.1N NaOH
3. extractionextract with methylene dichloride three times
4. dry with materialCombine the organic layers, dry over Na2SO4
5. filtrationfilter
6. concentrationconcentrate
7. customto give a residue
8. washChromatography (silica gel) eluting with 3.5% 2M NH3-methanol in methylene dichloride