Some tips on 2-Chloro-3-fluoroisonicotinic acid

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,628691-93-0, its application will become more common.

Application of 628691-93-0, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 628691-93-0 as follows.

2-Chloro-N-(4-(4,4-difluoropiperidin-1-yl)pyridin-3-yl)-3-fluoroisonicotinamideIn a 15 mL vial was dissolved 4-(4,4-difiuoiOpiperidin-l- yl)pyridin-3-amine (139 mg, 0.650 mmol) and 2-chloro-3-fluoroisonicotinic acid (103.8 mg, 0.591 mmol) in dimethylformamide (4 mL) to give a tan solution. HATU (450 mg, 1.183 mmol) and Hunig’s base (0,207 mL, 1,183 mmol) were added, and the mixture was stirred at rt for 22 h. It was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated. The residue was purified using silica gel flash chromatography, eluting with 50% ethyl acetate/hexane to afford the desired product (31.8 mg, 14.5%) as a tan oil: MS (ESI) (m/z) 371 (M+H)+; 1H NM (400 MHz, MeOD) delta 9.14 (s, lH)t 8.37 (d, J = 5.0 Hz, 1H), 8.30 (dd, J = 4.6, 3.7 Hz, 1H), 7.81 (t, J = 4.9 Hz, 1H), 7.39 (dd, J = 8.4, 4.4 Hz, 1H), 7.19 (d, J = 5.8 Hz, 1H), 3.38 – 3.31 (m, 2H), 3.25 – 3.18 (m, 2H), 2.16 – 2.02 (m, 2H), 2.01 – 1.91 (m, 2H); 1 F NMR (376 MHz, MeOD) delta -73.28 (s), -75.17 (s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,628691-93-0, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; LUO, Guanglin; CHEN, Ling; DUBOWCHIK, Gene M.; JACUTIN-PORTE, Swanee E.; SIVAPRAKASAM, Prasanna; MACOR, John E.; WO2015/69593; (2015); A1;,
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