反应详情

A mixture of 4-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]-N-methylpyrimidin-2-amine (C8, which can be prepared by the method of J. Sisko, U.S. Pat. No. 6,239,279 B1, May 29, 2001) (75 mg, 0.21 mmol), 1-isoxazol-3-ylethyl methanesulfonate (C7) (60 mg, 0.31 mmol) and cesium carbonate (139 mg, 0.43 mmol) in acetonitrile (2 mL) was heated at 70° C. for 24 hours. Removal of solvent under reduced pressure provided a residue, which was purified by silica gel chromatography (Eluants: 0%, then 5%, then 15% methanol in ethyl acetate). The resulting colorless oil was dissolved in ethyl acetate/heptane, then concentrated in vacuo to provide the product as a white solid. Yield: 57 mg, 0.13 mmol, 62%. APCI m/z 448.3 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.46 (d, J=6.9 Hz, 3H), 1.93-2.07 (m, 2H), 2.12-2.24 (m, 4H), 2.98-3.08 (m, 2H), 3.02 (d, J=5.0 Hz, 3H), 3.94 (q, J=6.9 Hz, 1H), 4.59 (br m, 1H), 5.14 (br d, J=5 Hz, 1H), 6.35 (d, J=1.7 Hz, 1H), 6.40 (d, J=5.0 Hz, 1H), 7.00 (dd, J=8.8, 8.8 Hz, 2H), 7.46 (dd, J=9.0, 5.5 Hz, 2H), 7.77 (s, 1H), 8.15 (br d, J=5 Hz, 1H), 8.38 (dd, J=1.7, 0.6 Hz, 1H).

1. customcan be prepared by the method of J
2. customRemoval of solvent under reduced pressure
3. customprovided a residue, which
4. customwas purified by silica gel chromatography (Eluants
5. dissolutionThe resulting colorless oil was dissolved in ethyl acetate/heptane
6. concentrationconcentrated in vacuo