With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.19788-37-5,4-(Chloromethyl)-3,5-dimethylisoxazole,as a common compound, the synthetic route is as follows.
To a solution of the product of Example 1B (120 mg, 0.40 mmol) in tetrahydrofuran (3 mL) at 0 C. was added NaH (95 weight %, 31 mg, 1.22 mmol). The mixture was allowed to warm to ambient temperature and 4-(chloromethyl)-3,5-dimethylisoxazole (88 mg, 0.61 mmol) was added. The resulting mixture was stirred at ambient temperature for 18 hours. The reaction was quenched with water (0.5 mL) and concentrated in vacuo. The residue was dissolved in a solvent mixture of dimethyl sulfoxide (3 mL), methanol (2 mL) and water (0.5 mL), filtered through a glass microfiber frit and purified by preparative HPLC [Waters XBridge C18 5 mum column, 50*100 mm, flow rate 90 mL/minute, 5-95% gradient of acetonitrile in buffer (0.025 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to give the titled compound (155 mg, 0.38 mmol, 94% yield). 1H NMR (400 MHz, methanol-d4) delta ppm 8.38 (s, 1H), 7.61 (td, J=7.7, 1.6 Hz, 1H), 7.58-7.51 (m, 1H), 7.49-7.34 (m, 3H), 7.13 (dd, J=8.5, 2.9 Hz, 1H), 7.10 (d, J=7.5 Hz, 1H), 4.36 (s, 2H), 4.12-3.94 (m, 2H), 3.58-3.43 (m, 2H), 2.46 (s, 3H), 2.31 (s, 3H); MS (ESI+) m/z 406 [M+H]+., 19788-37-5
19788-37-5 4-(Chloromethyl)-3,5-dimethylisoxazole 88246, aIsoxazoles compound, is more and more widely used in various fields.
Reference£º
Patent; AbbVie Inc.; Daanen, Jerome F.; DeGoey, David A.; Frost, Jennifer M.; Koenig, John R.; Latshaw, Steve; Matulenko, Mark; Scanio, Marc; Shi, Lei; Bunnelle, William H.; (128 pag.)US2016/75692; (2016); A1;,
Isoxazole – Wikipedia
Isoxazole | C3H3NO – PubChem