Some common heterocyclic compound, 35277-02-2, name is 4-Fluoro-1H-pyrazole, molecular formula is C3H3FN2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Quality Control of 4-Fluoro-1H-pyrazole
(5)-N-(2-Chloropyridin-4-yl)-3-(4-fluoro- lH-pyrazol- l-yl)-2-hydroxy-2-methylpropanam (0881) (0882) 1041 (0883) [00407] To a dry, nitrogen-purged 100 mL round-bottom flask equipped with a dropping funnel under argon atmosphere, NaH of 60% dispersion in mineral oil (96 mg, 2.4 mmol) was added in 10 mL of anhydrous THF solvent at ice-water bath. 4-Fluoro-lH-pyrazole (103 mg, 1.2 mmol) was added and the solution stirred 30 min at the ice-water bath. Into the flask, the solution of ( ?)-3-bromo- N-(2-chloropyridin-4-yl)-2-hydroxy-2-methylpropanamide (293 mg, 1.0 mmol) in 5 mL of anhydrous THF was added through dropping funnel under argon atmosphere at the ice- water bath and stirred overnight at RT. After adding 1 mL of H2O, the reaction mixture was condensed under reduced pressure, and then dispersed into 50 mL of EtOAc, washed with 50 mL (x 2) water, evaporated, dried over anhydrous MgS04, and evaporated to dryness. The mixture was purified with flash column chromatography using as an eluent EtOAc/hexane as a 1:2 ratio to produce compounds to produce the titled compound (55%) as a white solid. (0884) [00408] Compound 1041 was characterized as follows: lH NMR (400 MHz, CDCI3) delta 8.90 (bs, 1H, NH), 8.26 (d, = 5.6 Hz, 1H), 7.63 (s, 1H), 7.75 (d, = 4.2 Hz, 1H), 7.33 (d, = 4.2 Hz, 1H), 7.31 (dd, = 5.6, 1.2 Hz, 1H), 5.88 (s, 1H, OH), 4.53 (d, = 13.6 Hz, 1H), 4.14 (d, = 13.6 Hz, 1H), 1.45 (s, 3H); 19F NMR (CDCI3, decoupled) delta -176.47; MS (ESI) m/z 298.98 [M + H] +; 296.96 [M – H] .
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 35277-02-2, its application will become more common.
Reference:
Patent; UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION; NARAYANAN, Ramesh; MILLER, Duane; PONNUSAMY, Thamarai; HWANG, Dong-Jin; HE, Yali; (234 pag.)WO2017/214634; (2017); A1;,
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