These common heterocyclic compound, 518057-72-2, name is 5-Amino-2-fluorobenzamide, 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. category: amides-buliding-blocks
To a solution of 5-amino-2-fluoro-benzamide (0.88 g, 5.7 mmol) and DIEA (3.0 mL, 17 mmol) in THF (20 mL) and dichloromethane (10 mL) at 0 C was added a solution of 6-cyclopropyl-4- [2-methoxy-4-(trifluoromethoxy)phenoxy]pyridine-3-carbonyl chloride (2.1 g, 5.4 mmol) in dichloromethane. The reaction mixture was removed from the ice bath and stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was concentrated in vacuo and the resulting solid was purified using silica gel chromatography (0-60% ethyl acetate/hexanes) to provide N-(3 -carbamoyl -4-fluoro-phenyl)-6- cyclopropyl-4-[2-methoxy-4-(trifluoromethoxy)phenoxy]pyridine-3-carboxamide (1.1 g, 40%). ESI-MS m/z calc. 505.13, found 506.2 (M+l)+; retention time (Method B): 1.4 minutes (3 minute run). ‘H NMR (400 MHz, DMSO-d6) delta 10.41 (s, 1H), 8.55 (s, 1H), 7.99 (dd, J = 6.5, 2.8 Hz, 1H), 7.87 – 7.76 (m, 1H), 7.69 (d, J = 14.5 Hz, 2H), 7.45 (d, J = 8.8 Hz, 1H), 7.32 – 7.18 (m, 2H), 7.07 (ddd, J = 8.8, 2.8, 1.3 Hz, 1H), 6.59 (s, 1H), 3.80 (s, 3H), 2.07 (p, J = 6.7 Hz, 1H), 0.99 – 0.87 (m, 4H) ppm.
The synthetic route of 5-Amino-2-fluorobenzamide has been constantly updated, and we look forward to future research findings.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; AHMAD, Nadia; ANDERSON, Corey; ARUMUGAM, Vijayalaksmi; ASGIAN, Iuliana, Luci; CAMP, Joanne, Louise; FANNING, Lev Tyler, Dewey; HADIDA RUAH, Sara, Sabina; HURLEY, Dennis; SCHMIDT, Yvonne; SHAW, David; SHETH, Urvi, Jagdishbhai; THOMSON, Stephen, Andrew; (691 pag.)WO2019/14352; (2019); A1;,
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