Category: 425379-16-4

Reference of 425379-16-4, These common heterocyclic compound, 425379-16-4, name is 2-Bromo-3-fluorobenzonitrile, 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.

The product of Example 12 step a) (1.00 g, 4.57 mmol) and 2-BROMO- 3-FLUOROBENZONITRILE (0.91 g, 4.57 mmol) were suspended in 1, 2- dimethoxyethane (20 ml) and 2 N sodium carbonate (10 ml) and the mixture degassed with nitrogen for 30 min. TETRAKIS-TRIPHENYLPHOSPHINE palladium (0) (211 mg, 0.18 mmol) was added and the mixture was heated at 80C for 18 h. The mixture was allowed to cool to ambient temperature, DILUTED WITH ETHYL ACETATE (100 ML) AND WASHED WITH 2 N SODIUM HYDROXIDE solution (75 ml), water (50 ml) and brine (50 ml), dried over anhydrous sodium sulfate, filtered and evaporated to give a pale yellow oil. The oil was purified by flash column chromatography on silica eluting with 0-15% ETOAC/ISOHEXANE to give 0.39 g (29%) of the title compound as a colourless oil which solidified on standing: ON (400 MHz, CDCL3) 7.19 (1 H, ddd, J 8.0, 8.0, 1.0), 7.34-7. 38 (1 H, m), 7.44 (1 H, td, J9.0, 1.4), 7.50-7. 56 (1 H, m), 7.61 (1 H, ddd, J7. 8, 1.0, 0.6), 7. 68-7. 72 (1 H, m).

The synthetic route of 425379-16-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME LIMITED; WO2004/65388; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

425379-16-4, name is 2-Bromo-3-fluorobenzonitrile, belongs to nitriles-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Recommanded Product: 2-Bromo-3-fluorobenzonitrile

To a solution of 2-bromo-3-fluorobenzonitrile (10.0 g, 50 mmol) in sulfuric acid (22 mL) was added nitric acid (69%, 4.82 mL, 75 mmol) dropwise, maintaining the temperature between 5-10 C. The reaction mixture turned red-orange at the end of the addition. The reaction mixture was allowed to warm up to RT and was stirred for 1 hour. The reaction mixture was then poured onto crushed ice. The products were extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine (50 mL), dried (MgS04), filtered and concentrated under reduced pressure. The residue was suspended in MeOH (50 mL) and the mixture was briefly heated at reflux. After cooling to RT, a pale yellow precipitate was collected by vacuum filtration, washed with a small amount of MeOH and dried in the vacuum oven. The material was recrystallized from MeOH to afford 1 .77 g (14% yield) of the title compound as a yellow powder.1H NMR (500 MHz, DMSO-d6) delta [ppm] 8.77 (dd, J = 2.5, 1 .4 Hz, 1 H), 8.65 (dd, J = 8.3, 2.5 Hz, 1 H).LCMS (Analytical Method A): Rt = 1 .1 1 min, mass ion not observed.

The synthetic route of 425379-16-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeURLE, Stefan; DAVENPORT, Adam, James; STIMSON, Christopher; CARR, James, Lindsay; BUBERT, Christian, Abingdon; MARLIN, Frederic, Jacques; NAGEL, Jens; SCHMIDT, Nicole; ROTGERI, Andrea; IRLBACHER, Horst; (378 pag.)WO2018/114783; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 425379-16-4, name is 2-Bromo-3-fluorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H3BrFN

(4aS,5S)-1-(4-Fluorophenyl)-4a-methyl-5-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl]-1,4,4a,5,6,7-hexahydrocyclopenta[f]indazol-5-ol (13) (200 mg, 0.456 mmol), 2-bromo-3-fluorobenzonitrile (91 mg, 0.456 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (30 mg, 0.046 mmol), and Cs2CO3 (446 mg, 1.37 mmol) in degassed toluene(0.9 mL)/water (0.3 mL) were heated at 80 C for 1 h. The reaction was quenched with water and extracted with EtOAc (×3). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on Silica, eluting with a gradient of 0-100% EtOAc in hexanes to afford 14 (139 mg, 71%) as a white solid; 1H NMR (CDCl3, 500 MHz): delta 7.50 (s, 1H), 7.44-7.40 (m, 3H), 7.33-7.25 (m, 2H), 7.17 (t, J = 8.3 Hz, 2H), 6.15 (s, 1H), 3.18 (td, J = 12.7, 4.5 Hz, 1H), 2.97 (td, J = 12.6, 4.8 Hz, 1H), 2.84 (d, J = 15.4 Hz, 1H), 2.65 (dd, J = 19.0, 9.8 Hz, 1H), 2.53-2.42 (m, 2H), 2.34-2.26 (m, 1H), 2.07-1.98 (m, 1H), 1.88-1.80 (m, 1H), 1.75-1.67 (m, 1H), 1.17 (s, 3H), 0.90-0.82 (m, 1H); MS (ESI): m/z = 432.09 (MH+), 100% pure by LC-MS.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 425379-16-4.

Synthetic Route of 425379-16-4, 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 425379-16-4 as follows.

2-Bromo-3-fluorobenzonitrile (1 .0 g, 5.0 mmol) and (1 H-pyrazol-5-yl)boronic acid (647 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 ml_) then treated with NaHCO3 (1260 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3) (288 mg, 0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. Cooled to 23 C filtered and solid rinsed with EtOAc and the layers separated. The organic layers were combined, dried and concentrated under reduced pressure.Chromatography (0-30% ethyl acatate / hexanes) afforded 3-fluoro-2-(1 H- pyrazol-5-yl)benzonitrile (178 mg,19%).

According to the analysis of related databases, 425379-16-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BRANSTETTER, Bryan, James; LETAVIC, Michael, A.; LY, Kiev, S.; RUDOLPH, Dale, A.; SAVALL, Brad, M.; SHAH, Chandravadan, R.; SHIREMAN, Brock, T.; WO2011/50200; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 425379-16-4, These common heterocyclic compound, 425379-16-4, name is 2-Bromo-3-fluorobenzonitrile, 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.

The product of Example 12 step a) (1.00 g, 4.57 mmol) and 2-BROMO- 3-FLUOROBENZONITRILE (0.91 g, 4.57 mmol) were suspended in 1, 2- dimethoxyethane (20 ml) and 2 N sodium carbonate (10 ml) and the mixture degassed with nitrogen for 30 min. TETRAKIS-TRIPHENYLPHOSPHINE palladium (0) (211 mg, 0.18 mmol) was added and the mixture was heated at 80C for 18 h. The mixture was allowed to cool to ambient temperature, DILUTED WITH ETHYL ACETATE (100 ML) AND WASHED WITH 2 N SODIUM HYDROXIDE solution (75 ml), water (50 ml) and brine (50 ml), dried over anhydrous sodium sulfate, filtered and evaporated to give a pale yellow oil. The oil was purified by flash column chromatography on silica eluting with 0-15% ETOAC/ISOHEXANE to give 0.39 g (29%) of the title compound as a colourless oil which solidified on standing: ON (400 MHz, CDCL3) 7.19 (1 H, ddd, J 8.0, 8.0, 1.0), 7.34-7. 38 (1 H, m), 7.44 (1 H, td, J9.0, 1.4), 7.50-7. 56 (1 H, m), 7.61 (1 H, ddd, J7. 8, 1.0, 0.6), 7. 68-7. 72 (1 H, m).

The synthetic route of 425379-16-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME LIMITED; WO2004/65388; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 425379-16-4, A common heterocyclic compound, 425379-16-4, name is 2-Bromo-3-fluorobenzonitrile, molecular formula is C7H3BrFN, 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.

Step 3. 2′,6-Difluoro-5 ‘-(5 -(2-hydroxy- 1.1.1,3.3.3 – c -propan-2- ylV 1 H- benzo 1imidazol-l-yl biphenyl-2-carbonitrile (108): A mixture of lOu (1.7 g, 4.78 mmol), bis(pinacolato)diboron (1.47 g, 5.8 mmol) and KOAc (1.18 g, 12.0 mmol) in dioxane (30 mL) was purged with nitrogen for 5 minutes. Bis(triphenylphosphine)palladium(II)- dichloride (270 mg, 0.38 mmol) was added and the mixture was heated at 120 C overnight. The mixture was diluted with EtOAc (200 mL) and the solution was washed with water (2 x 30 mL) and brine, then dried (Na S04). After concentrating to dryness the material was dissolved in MeOH (30 mL) and concentrated to dryness again. The concentration step from MeOH was repeated a total of five times until about 2.1 g of a tan colored solid was obtained. This intermediate (2.1 g) was stirred in THF (20 mL) and water (10 mL) and was treated with 3-fluoro-2-bromo-l-cyanobenzene (1.2 g, 6 mmol) and K2C03 (1.5 g, 10.8 mmol). The mixture was purged with nitrogen for five minutes, then bis(di-t-butylphosphine) ferrocene palladium(II)dichloride (130 mg, 0.2 mmol) was added. The solution was heated at 60 C overnight. The cooled mixture was diluted with EtOAc (120 mL) and washed with water (30 mL). The organic phase was dried (Na2S04) and concentrated. The crude product was purified on an Analogix automated chromatography system eluting with 0-3% MeOH/CH2Cl2. The partially purified mixture was further purified on a reverse-phase CI 8 column eluting with 0-50% acetonitrile/water. The purest fractions were collected and concentrated to remove acetonitrile and the solid was isolated by filtration. This solid was passed through a short silica gel column eluting with 3% MeOH/CH2Cl2 to give 320 mg (17%) of 108 with 99.8% purity. 1H-NMR (300 MHz, CDC13): delta 1.89 (s, 1H), 7.42-7.44 (m, 0.19H), 7.45-7.47 (m, 0.65H), 7.47-7.50 (m, 0.76H), 7.51 (app d, J= 1.46, 0.33H), 7.53-7.67 (m, 6H), 7.99 (dd, J= 0.7, 1.7, 1H), 8.12 (s, 1H). 13C-NMR (75 MHz, CDC13): delta 109.95, 116.31, 117.79, 118.11, 120.75, 121.05, 121.32, 127.03, 127.15, 127.38, 129.32, 129.37, 131.15, 131.27, 132.53, 142.47, 143.92, 144.65, 158.05, 161.41. HPLC (method: Waters Atlantis T3 2.1 column 2.1 x 50 mm 3mu?iota – gradient method 5-95% ACN + 0.1% formic acid in 14 min with 4 min hold at 95% ACN+0.1% formic acid; wavelength: 305 nm):retention time: 5.85 min; 99.8% purity. MS (M+H): 396.3. Elemental Analysis(C^HnDgFa^O): Calculated: C=69.87, H=4.33, F=9.61, N=10.63. Found: C=79.27, H=4.05, F=9.63, N=10.53.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; CONCERT PHARMACEUTICALS, INC.; LIU, Julie, F.; HARBESON, Scott, L.; WO2011/47315; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts