With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.58584-86-4, name is Ethyl 2,6-dichloronicotinate, molecular formula is C8H7Cl2NO2, molecular weight is 220.05, as common compound, the synthetic route is as follows.Formula: C8H7Cl2NO2
3-[(2,2-Difluoro-1-methyl-cyclopropyl)methoxy]-1H-pyrazole (490 mg, 2.604 mmol) was dissolved in DMF (5 mL). Ethyl 2,6-dichloropyridine-3-carboxylate (approximately 573.0 mg, 2.604 mmol) was added followed by 1,4-diazabicyclo[2.2.2]octane(approximately 58.42 mg, 0.5208 mmol) and finely ground potassium carbonate (approximately 539.8 mg, 3.906 mmol). The reaction mixture was allowed to stir overnight at room temperature. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2× 50 mL). The combined organic layers were then washed with brine (1× 75 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was isolated by silica gel column chromatography eluting with a 0-20% EtOAc/hexane gradient on a 40 gram silica gel column. Ethyl 2- chloro-6-[3-[(2,2-difluoro-1-methyl-cyclopropyl)methoxy]pyrazol-1-yl]pyridine-3- carboxylate (797 mg, 82%) was obtained as a white solid.1H NMR (400 MHz, DMSO- d6) delta 8.46 (dd, J = 2.8, 0.9 Hz, 1H), 8.41 (dd, J = 8.4, 0.9 Hz, 1H), 7.75 (dd, J = 8.5, 0.9 Hz, 1H), 6.27 (dd, J = 2.9, 0.9 Hz, 1H), 4.44 – 4.37 (m, 1H), 4.37 – 4.31 (m, 2H), 4.17 (d, J = 10.8 Hz, 1H), 1.67 (q, J = 8.9 Hz, 1H), 1.42 (q, J = 8.4 Hz, 1H), 1.38 – 1.30 (m, 6H). ESI-MS m/z calc.371.08484, found 372.0 (M+1)+; Retention time: 2.09 minutes.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,58584-86-4, Ethyl 2,6-dichloronicotinate, and friends who are interested can also refer to it.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; ABELA, Alexander, Russell; ALCACIO, Timothy; ANDERSON, Corey; ANGELL, Paul, Timothy; BAEK, Minson; CLEMENS, Jeremy, J.; CLEVELAND, Thomas; FERRIS, Lori, Ann; GROOTENHUIS, Peter Diederik, Jan; GROSS, Raymond, Stanley; GULEVICH, Anton; HADIDA RUAH, Sara, Sabina; HSIA, Clara, Kuang-Ju; HUGHES, Robert, M.; JOSHI, Pramod, Virupax; KANG, Ping; KESHAVARZ-SHOKRI, Ali; KHATUYA, Haripada; KRENITSKY, Paul, John; MCCARTNEY, Jason; MILLER, Mark, Thomas; PARASELLI, Prasuna; PIERRE, Fabrice Jean, Denis; SHI, Yi; SHRESTHA, Muna; SIESEL, David, Andrew; STAVROPOULOS, Kathy; TERMIN, Andreas, P.; UY, Johnny; VAN GOOR, Fredrick, F.; YOUNG, Tomothy, John; ZHOU, Jinglan; (398 pag.)WO2018/107100; (2018); A1;,
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