反应详情

To a solution of 2-(3-((5-(piperidin-4-yl)pyrimidin-4-yl)oxy)azetidin-1-yl)quinoline hydrochloride in CH2Cl2 (10 mL) were added Et3N (100 mg, 0.99 mmol) and acetyl chloride (62 mg, 0.79 mmol). The reaction mixture was stirred at room temperature for 1 hour, then diluted with CH2Cl2 (20 mL), washed with water (20 mL). The organic layer was washed with brine (20 mL), dried over Na2SO4, and filtered, evaporated to give the crude product. Purified by column chromatography, and followed by prep. HPLC (10% to 80% water/MeCN) to give 1-(4-(4-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-5-yl)piperidin-1-yl)ethanone (34 mg, 0.08 mmol, yield 13%). M+1 IC50 (uM) 404 0.765 1H NMR (CDCl3, 400 MHz) δ (ppm) 8.73 (s, 1H), 8.44 (s, 1H), 8.14 (d, J=9.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.75-7.65 (m, 2H), 7.47-7.40 (m, 1H), 6.64 (d, J=9.2 Hz, 1H), 5.71 (s, 1H), 5.04-4.98 (m, 2H), 4.79-4.71 (m, 2H), 4.68-4.63 (m, 1H), 3.97-3.93 (m, 1H), 3.26-3.19 (m, 1H), 3.11-3.04 (m, 1H), 2.71-2.64 (m, 1H), 2.14 (s, 3H), 2.03-1.89 (m, 2H), 1.69-1.63 (m, 2H).

1. washwashed with water (20 mL)
2. washThe organic layer was washed with brine (20 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. customevaporated
6. customto give the crude product
7. customPurified by column chromatography