反应详情

To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (200 mg, 0.45 mmol) (prepared according to WO 02/48115, example 2D) in tetrahydrofurane (4 ml), is added 2-aminomethyloxetane (the product of step 2) (79 mg, 0.91 mmol), and the mixture is heated to reflux for 30 minutes. The solution is allowed to cool to ambient temperature and the solvent evaporated in vacuo. The residue is purified by prep. HPLC (hexane/ethyl acetate gradient on LiChrospher Si 60, Merck NW25 column) to afford 180 mg (71%) of the title compound as a white solid. [1H-NMR (CDCl3): 10.21 (s, 1H), 8.48 (d, 1H), 7.88 (d, 1H), 7.41 (m, 1H), 7.32 (s, 1H), 7.29 (m, 2H), 6.63 (m, 1H), 4.98 (m, 1H), 4.68 (m, 1H), 4.48 (m, 1H), 3.71 (m, 1H), 3.59 (m, 1H), 2.68 (m, 1H), 2.43 (m, 1H), 2.19 (s, 3H); MS (electrospray ES+): 528, 530 ((M+H)+)].

1. temperaturethe mixture is heated
2. temperatureto reflux for 30 minutes
3. customthe solvent evaporated in vacuo
4. customThe residue is purified by prep