These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,17282-04-1, its application will become more common.
Application of 17282-04-1, 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 17282-04-1 as follows.
To a degassed solution of [5-FLUORO-2- (4,] 4,5, 5-tetramethyl- [1, 3,2] dioxaborolan-2-yl) benzonitrile (5.55 g, 22.46 [MMOL),] 2-chloro-3- [FLUOROPYRIDINE] (2.95 g, 22.46 mmol), potassium fluoride (4.3 g, 74.14 mmol) and tris (dibenzylideneacetone) [DIPALLADIUM (0)] (0.824 g, 0. 89 mmol) in THF (80 ml) and water [(8] ml) was added tri (tert-butyl) phosphine (0.51M solution in hexane; 3.52 ml, 1.79 mmol). The reaction was heated at [70C] for 48 h, then allowed to cool to ambient temperature. The reaction mixture was filtered through a catalyst filter, and the filtrate diluted with ethyl acetate (400 ml) and washed with water (2 x 100 ml). The organic phase was separated, dried (MgSO4), filtered and adsorbed onto silica gel. The crude product was chromatographed on silica, eluting with 10% ethyl acetate in isohexane, to give [5-FLUORO-2- (3-FLUOROPYRIDIN-2-YL)] benzonitrile as a white solid (3.02 [G)] : [8H] (400 MHz, [CD13)] 7. [40-7.] 45 (2H, m), 7.51-7. 61 (2H, m), 7.72-7. 76 [(1H,] m), 8.58-8. 60 [(1H,] m); m/z (ES+) 217. To a solution of [5-FLUORO-2- (3-FLUOROPYRIDIN-2-YL)] benzonitrile (1 g, 4.62 mmol) in dichloromethane (10 ml) at [0C] was added urea hydrogen peroxide addition compound (0.91 g, 9.71 mmol) followed by trifluoroacetic anhydride (1.94 g, 1.30 ml, 9.25 mmol) and the mixture warmed to ambient temperature and stirred for 18 h. The reaction was quenched with [NA2S203] (saturated solution; 2 ml) and poured onto 0.5N HCl (20 ml). The aqueous phase was extracted with dichloromethane (2 x 100 ml) and the combined organics dried over [MGS04,] filtered and evaporated to give a red oil. The crude product was chromatographed on silica (0 to 5% methanol in dichloromethane) to give [5-FLUORO-2- (3-FLUORO-1-OXYPYRIDIN-2-] yl) benzonitrile as an amber oil which crystallised on standing (0.687 [G)] : [SN] (400 MHz, CDCl3) 7.24-7. 27 [(1H,] m), 7.36-7. 39 [(1H,] m), 7.45-7. 49 [(1H,] m), 7.56 [(1H,] dd, [J 2.] 7,7. 8), 7.65 [(1H,] dd, [J 5.] 3, 8. 7), 8.29 [(1H,] d, [J 6.] 6); [M/Z] (ES+) 233. To a solution of [5-FLUORO-2-(3-FLUORO-1-OXYPYRIDIN-2-YL)] benzonitrile (0.67 g, 2.88 mmol) in chloroform (3 ml) was added phosphorus oxychloride (11.06 g, 72. 18 mmol) and the mixture heated at reflux for 2 h. After cooling to ambient temperature, the reaction was poured onto ice (150 g) and stirred for 15 mins. Solid sodium carbonate was then added portionwise until pH = 10. The mixture was then extracted with dichloromethane (2 x 150 ml) and the combined organics dried [(MGSO4),] filtered and evaporated to give a cream-coloured solid. The crude product was chromatographed on silica, eluting with 50-25% isohexane in dichloromethane, to give two products. Less polar product 2- (6-chloro-3- [FLUOROPYRIDIN-2-YL)-5-FLUOROBENZONITRILE] (258 mg): aH (400 MHz, CDCl3) 7.41-7. 45 (2H, m), 7.53 [(1H,] dd, [J 2.] 6,7. 9), 7.57 [(1H,] t, [J 8.] 6), 7.74 [(1H,] dd, J 5.4, 8.8) ; m/z (ES+) 251. More polar product [2- (4-CHLORO-3-FLUOROPYRIDIN-] 2-yl)-5-fluorobenzonitrile (115 mg): [8H] (400 MHz, [CD13)] 7.41-7. 45 [(1H,] m), 7.49 [(1H,] t, [J 5.] 1), 7. 55 [(1H,] dd, [J 2.] 6,7. 9), 7.73 [(1H,] dd, [J 1.] 3,14. 1), 8. 47 [(1H,] d, [J 5.] 1); m/z (ES+) [251.] To [2- (8-FLUOROIMIDAZO [1,] 2-a] pyridin-7-yl) propan-2-ol (0.21 g, 1.10 mmol), [2- (6-CHLORO-3-FLUOROPYRIDIN-2-YL)-5-FLUOROBENZONITRILE] (0.25 g, 1.00 mmol) and palladium acetate (0.011 g, 0.05 mmol) in [N, N-] dimethylacetamide (2 ml) was added triphenylphosphine (0.013 g, 0.05 mmol) followed by potassium acetate (0.14 g, 1.51 mmol) and the mixture heated at [130C] for 2 h. The reaction was cooled to ambient temperature, diluted with methanol (8 ml) and 2 drops of acetic acid were added. The mixture was poured onto a strong cation exchange cartridge and eluted with several column lengths of methanol. Several column lengths of 2N ammonia in methanol were then eluted to recover the product. The pale yellow oil was chromatographed on silica, eluting with 3% methanol in dichloromethane, to give the title material as a white powdery solid. Recrystallised from ethyl [ACETATE/ETHER] to afford the title compound (215 mg): aH (400 MHz, CDCl3) 1.73 (6H, s), 2.07 [(1H,] s), 7.26 [(1H,] d, J 14.4), 7.45-7. 49 [(1H,] m), 7.61 [(1H,] dd, [J2.] 6,7. 9), 7.67 [(1H,] t, [J 9.] 0), 7.77-7. 80 [(1H,] m), 7. 88 [(1H,] dd, [J 3.] 3,8. 9), 8. 15 [(1H,] s), 9.59 [(1H,] d, [J 7.] 3); m/z [(ES+)] 409.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,17282-04-1, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME LIMITED; WO2003/99817; (2003); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem