Electric Literature of 58584-86-4 , The common heterocyclic compound, 58584-86-4, name is Ethyl 2,6-dichloronicotinate, molecular formula is C8H7Cl2NO2, its 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.
A mixture of 3-(dispiro[2.0.2. l]heptan-7-ylmethoxy)-lH-pyrazole (0.94 g, 4.9 mmol), ethyl 2,6-dichloropyridine-3-carboxylate (1.15 g, 5.23 mmol), potassium carbonate (0.83 g, 6.0 mmol), and l,4-diazabicyclo[2.2.2]octane (0.12 g, 1.1 mmol) in DMSO (16 mL) was stirred for 24 hours. The reaction was diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine and water, dried over sodium sulfate, and evaporated under vacuum. The residue was purified by silica gel column chromatography eluting with 0-20% ethyl acetate in hexanes to give ethyl 2-chloro-6-(3-(dispiro[2.0.2.1]heptan-7-ylmethoxy)-lH-pyrazol-l-yl)nicotinate (1.39 g, 75% yield) as a colorless solid. ESI-MS m/z calc. 373.11932, found 374.2 (M+l)+; Retention time: 0.87 minutes. *H NMR (400 MHz, Chloroform-d) delta 8.36 (d, J = 2.8 Hz, 1H), 8.27 (d, J = 8.5 Hz, 1H), 7.72 (d, J = 8.5 Hz, 1H), 5.96 (d, J = 2.9 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 4.30 (d, J = 7.0 Hz, 2H), 1.94 (t, J = 7.0 Hz, 1H), 1.42 (t, J = 7.1 Hz, 3H), 1.02-0.89 (m, 4H), 0.75-0.65 (m, 2H), 0.65-0.53 (m, 2H)
The synthetic route of 58584-86-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; ALCACIO, Timothy; BAEK, Minson; GROOTENHUIS, Peter; HADIDA RUAH, Sara, Sabina; HUGHES, Robert, M.; KESHAVARZ-SHOKRI, Ali; MCAULEY-AOKI, Rachel; MCCARTNEY, Jason; MILLER, Mark, Thomas; VAN GOOR, Fredrick; ZHANG, Beili; ANDRESON, Corey; CLEVELAND, Thomas; FRIEMAN, Bryan, A.; KHATUYA, Haripada; JOSHI, Pramod, Virupax; KRENITSKY, Paul, John; MELILLO, Vito; PIERRE, Fabrice, Jean Denis; TERMIN, Andreas, P.; UY, Johnny; ZHOU, Jinglan; ABELA, Alexander, Russell; BUSCH, Brett, Bradley; PARASELLI, Prasuna; SIESEL, David, Andrew; (329 pag.)WO2018/64632; (2018); A1;,
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