Month: September 2021

Electric Literature of 3939-09-1, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 3939-09-1, name is 2,4-Difluorobenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Benzyl alcohol (0.77 g, 7.2 mmol) was added to a stirred suspension of potassium tert-butoxide (0.97 g, 8.6 mg) in dioxane (15 ml) at room temperature. After 10 minutes of stirring at room temperature 2,4-difiuorobenzonitrile (1.00 g, 7.2 mmol) was added in one portion. After another 90 minutes water (10 ml) was added and the mixture extracted with diethyl ether (3×10 ml), the combined organic phases were dried using a phase separator and concentrated to solids. The crude material was purified by column (0491) chromatography using silicon dioxide gel, eluting with 25-50% dichloromethane in petroleum ether to afford 2-(benzyloxy)-4-fluorobenzonitrile as a white solid (1.33 g, 81%). (0492) [00317] A cold solution of borane (1.4 ml, 1 M in tetrahydrofuran) was added to 2- (benzyloxy)-4-fluorobenzonitrile (208 mg, 915 mutauetaomicron). After 15 hours of stirring at room temperature additional borane (1.4 ml, 1 M in tetrahydrofuran) was added. After another 19 hours of stirring additional borane (1.0 ml, 1 M in tetrahydrofuran) was added. After 3 hours the mixture was added to sodium hydroxide (5 ml, 1 M aqueous), extracted with ethyl acetate (3×5 ml), the combined organic phases were dried using a phase separator and concentrated afford [2-(benzyloxy)-4-fluorophenyl]methanamine as oil (260 mg, quantitative). This material was used without further purification. (0493) [00318] N-Methyl-4-piperidone (150 mg, 1.32 mmol) was added to a stirred solution of [2-(benzyloxy)-4-fluorophenyl]methanamine (204 mg, 882 mueta omicron) in ethanol (5 ml), after 5 minutes sodium triacetoxyborohydride (372 mg, 1.76 mmol) was added. After 6 hours the reaction mixture was concentrated, redissolved in dichloromethane (5 ml), washed with sodium hydroxide (5 ml, 1 M aqueous), the aqueous phase was extracted with additional dichloromethane (2×1 ml), the combined organic phases were dried using a phase separator, and concentrated to afford the desired intermediate as a yellow oil (253 mg, 87 %).

The synthetic route of 2,4-Difluorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ACADIA PHARMACEUTICALS INC.; BURSTEIN, Ethan, S.; OLSSON, Roger; BORGSTROeM, Bjoern, Gustav; JANSSON, Karl, Erik; SKOeLD, Niklas, Patrik; VON WACHENFELDT, Henrik; WAHLSTROeM, Larisa, Yudina; (250 pag.)WO2019/40107; (2019); A1;,
Nitrile – Wikipedia,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 52133-67-2, name is Ethyl 2-cyano-4,4-diethoxybutyrate, A new synthetic method of this compound is introduced below., Application In Synthesis of Ethyl 2-cyano-4,4-diethoxybutyrate

2-Methyl-4-hydroxypyrrolo[2,3-d]pyrimidine (3).; Acetamidine hydrochloride (2, 0.05 mol, 4.7 g) was added to the 0.1 M sodium ethoxide solution (75 ml) and kept stirring under room temperature for 0.5 h. After removing the formed sodium chloride by filtration, the filtrate was added the ethyl alpha-cyano-gamma,gamma-diethoxybutyrate (1, 0.05 mol, 11.5 g) and the solution was heated under reflux for 5 h. After the removal of most solvent under vacuum, acetic acid was added to adjust the pH to 7.0 and 10.8 g precipitation as white powder. Ethanol (110 ml) with concentrated sulfuric acid (2 ml) was added to the collected powder and was refluxed for 2 h. By the end of the reaction an equal volume of water was added and kept at 4° C. overnight. The pyrrolopyrimidine 3 precipitated as white powder (2.1 g) was used for next step without further purification.

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; Gangjee, Aleem; US2010/10016; (2010); A1;,
Nitrile – Wikipedia,
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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 41171-91-9 as follows. Formula: C6H7NO

To the solution of 3-cyanocyclopentanone prepared above (91.6 g) in MeOH (1300 ml) was added NaBH4 (32.0 g) in portions while maintaining the temperature between 20- 30 C. After the addition was completed the mixture was stirred at rt for 30min. The mixture was evaporated and purification of the residue by column chromatography on silica gel (50 % petroleum ether/EtOAc) afforded 3-Hydroxy-cyclopentanecarbonitrile (62.0 g) as a colorless oil. T

According to the analysis of related databases, 41171-91-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; BERGERON, Philippe; BODIL VAN NIEL, Monique; DRAGOVICH, Peter; HURLEY, Christopher; KULAGOWSKI, Janusz; LABADIE, Sharada; MCLEAN, Neville James; MENDONCA, Rohan; PULK, Rebecca; ZAK, Mark; WO2013/7765; (2013); A1;,
Nitrile – Wikipedia,
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Reference of 198633-76-0,Some common heterocyclic compound, 198633-76-0, name is 2-Fluoro-6-methylbenzonitrile, molecular formula is C8H6FN, 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) 3-Bromo-6-fluoro-2-methylbenzonitrile To a cooled (0 C.) solution of 2-fluoro-6-methylbenzonitrile (2 g, 14.8 mmol) in concentrated sulfuric acid (40 mL) was added NBS (2.7 g, 15.6 mmol). The resulting residue was stirred at 0 C. for 3 hrs and poured into ice-water (400 mL). The resulting solution was extracted three times with EtOAc (80 mL) and the combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography to yield 3-bromo-6-fluoro-2-methylbenzonitrile.

The synthetic route of 198633-76-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Pharmaceutica NV; Sui, Zhihua; Subasinghe, Nalin; US2014/275172; (2014); A1;,
Nitrile – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 2032-34-0, name is 3,3-Diethoxypropanenitrile, belongs to nitriles-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 2032-34-0, Quality Control of 3,3-Diethoxypropanenitrile

Step 1. l-cyclopropyl-lH-pyrazol-5-amine [0634] A 100-mL round-bottom flask was charged with 3,3-diethoxypropanenitrile (0.600 g, 4.19 mmol), cyclopropylhydrazine di-hydrochloride (0.610 g, 4.21 mmol) and ethanol (20 mL), and the resulting solution stirred for 18 h at 80 C. The reaction mixture was cooled to room temperature and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 10: 1, dichloromethane/methanol) to afford l-cyclopropyl-lH-pyrazol-5-amine (0.206 g, 36% ) as light yellow oil. MS (ESI, pos. ion) m/z 124[M+H]+.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; BAIR, Kenneth W.; HERBERTZ, Torsten; KAUFFMAN, Goss Stryker; KAYSER-BRICKER, Katherine J.; LUKE, George P.; MARTIN, Matthew W.; MILLAN, David S.; SCHILLER, Shawn E. R.; TALBOT, Adam C.; WO2015/74064; (2015); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 57381-37-0, These common heterocyclic compound, 57381-37-0, name is 2-Bromo-5-chlorobenzonitrile, 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.

GammaAlpha1 l-(2-Bromo-5-chloro-phenyl)cvclopropanamine To a stirred solution of 2-bromo-5-chlorobenzonitrile (10 g, 46 mmol) and Ti(Oi-Pr)4 (16.64 mL, 55 mmol) in THF (200 mL) at -78C was added EtMgBr (138 mL, 138 mmol) drop wise. The reaction mixture was allowed to warm up to room temperature and stirred for 2 hours. BF3-Et20 (17.2 mL) was added, and the solution was stirred for another 16 hours before it was quenched with aq. HCl solution and washed with EtOAc. The aqueous phase was adjusted to pH – 10 with aq. NaOH solution, and exacted with EtOAc three times. The combined organic layers were concentrated to give a crude product which was purified by silica gel flash chromatography to afford title compound (2 g, 17.6%). MS: 246.7 (M+H+, 1C1) as oil.

The synthetic route of 57381-37-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; AEBI, Johannes; AMREIN, Kurt E.; CHEN, Junli; HORNSPERGER, Benoit; KUHN, Bernd; LIU, Yongfu; LI, Dongbo; MAERKI, Hans Peter; MARTIN, Rainer E.; MAYWEG, Alexander; TAN, Xuefei; WU, Jun; YU, Jianhua; (109 pag.)WO2016/55394; (2016); A1;,
Nitrile – Wikipedia,
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Reference of 13544-06-4, 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 13544-06-4 as follows.

Step 1. Preparation of 2-Methyl-2-(2-nitro-4- trifluoromethyl-phenyl) -propionitrile; The title compound was synthesized according to a method described in Prasad, G. , J. Org. Chem. 1991,56, 7188-7190. To a yellow-brown solution of (2-Nitro-4-trifluoromethyl- phenyl) -acetonitrile (2.5 g, 11 mmol), 18-crown-6 (0.72 g, 2.7 mmol), and methyl iodide (1.5 mL, 24 mmol) in dry THF under nitrogen at-78 degrees C was added potassium tert- butoxide (2.7 g, 24 mmol) in one portion. The reaction immediately became a deep purple color. The reaction was allowed to stir for 2 h at-78 degrees C, and was then warmed to ambient temperature. A water-cooled reflux condenser was added and the solution heated to 70 degrees C under nitrogen. Over 40 minutes, the color changed from dark purple to cloudy gray. The mixture was allowed to cool to room temperature, and was concentrated in vacuo. The resulting material was partitioned between 1 N HCI and EtOAc. The organic layer was washed once with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a brown oil which was judged to be primarily monoalkylated nitrile. The crude material was resubjected to the reaction conditions using 18-crown-6 (0.72 mg, 2.7 mmol), methyl iodide (0.75 mL, 12 mmol), and potassium tert- butoxide (1.4 g, 12 mmol) as before, with the following modifications: the reaction was allowed to stir only 10 min. at-78 degrees C before being warmed to room temperature, and the reaction vessel was sealed and heated to 70 degrees C for 2 h. Upon cooling to room temperature, the reaction was quenched and worked up as before. Purification by flash chromatography afforded the desired product as a light brown solid. MS (M+H) + = 259; Calc’d 258.20 for C11H9F3N2O2.

According to the analysis of related databases, 13544-06-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; WO2005/113494; (2005); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 115279-57-7, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 115279-57-7, name is 2-(4-Aminophenyl)-2-methylpropanenitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Ethyl 4,6-dichloro-1,5-naphthyridine-3-carboxylate (6.4 g, 23.6 mmol) and 2-(4-aminophenyl)-2-methylpropionitrile (5.6 g, 35 mmol) were dissolved in tert-butanol (200 mL), to the system added potassium carbonate (16.4 g, 119 mmol), and the reaction mixture was stirred under reflux for 2 h. After confirming a disappearance of the raw materials by a thin layer chromatography plate (ethyl acetate:petroleum ether=1:3), the reaction mixture was suction filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was washed with diethyl ether to give 8.1 g of a pale yellow solid.

The synthetic route of 2-(4-Aminophenyl)-2-methylpropanenitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; XUANZHU PHARMA CO., LTD.; Wu, Frank; Zhang, Yan; US2015/166539; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 3215-64-3, name is 2-(2,6-Dichlorophenyl)acetonitrile, belongs to nitriles-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 3215-64-3, Quality Control of 2-(2,6-Dichlorophenyl)acetonitrile

4-amino-2-methylsulfanyl-pyrimidine-5-carbaldehyde (l-2a) (3.1 g, 18 mmol) was dissolved in 40 rtiL anhydrous dimethylformamide and cooled in an ice/methanol bath (-10 C) for 15 minutes under an atmosphere of nitrogen. Sodium hydride (0.73 g, 18 mmol) divided into 5 portions was added over the course of 5 minutes keeping the reaction mixture cooled with stirring. After an additional 5 minutes, a solution of 2,6-dichlorobenzylacetonitrile (1-la) (4.9 g, 27 mmol) in 12 mL anhydrous dimethylformamide was added drop wise via syringe. The resulting mixture was stirred at -10 C for 30 minutes then allowed to warm to room temperature overnight after which time the reaction mixture was cooled in an ice bath and slowly quenched with 50 mL saturated NEUCl. After stirring for 20 minutes the product was extracted into DCM. The combined DCM extracts were dried over MgSCk, filtered, and concentrated under reduced pressure. The residue was re-dissolved in ethyl acetate and washed with brine. The organic layer was filtered through a sintered glass funnel and the filtrate was dried over sodium sulfate, filtered, and concentrated under reduced pressure to dryness. The residue was purified by silica gel chromatography eluting with ethyl acetate/dichloromethane to afford 708 mg (11%) 6-(2,6- dichlorophenyl)-2-methylsulfanyl-pyrido[2,3-d]pyrimidin-7-amine (l-3a). LCMS (ESI):[M+H]? = 336.9

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(2,6-Dichlorophenyl)acetonitrile, and friends who are interested can also refer to it.

Reference:
Patent; ACHAOGEN, INC.; COHEN, Frederick; KANE, Timothy Robert; DOZZO, Paola; HILDEBRANDT, Darin James; LINSELL, Martin Sheringham; MACHAJEWSKI, Timothy D.; MCENROE, Glenn A.; (172 pag.)WO2018/23081; (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. 621-50-1, name is 2-(3-Nitrophenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 2-(3-Nitrophenyl)acetonitrile

To a solution of 3-nitro-phenyl-acetonitrile (3.20 g, 19.7 mmol) in MeOH(50 mL) was added Pd/C (10% wt, -50% H20, 0.32 g) and the mixture was placed under H2 (80 psi) and stirred for 2 days at 22 0C. The reaction mixture was filtered through Celite and the filtrate concentrated in vacuo to give crude product as a yellow oil. The residue was purified by silica gel chromatography (ISCO, elution with 0-10% ethyl acetate in hexanes) to give xix-1-1 (1.15 g, 44%): MS m/z = 133 (M-H).

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 621-50-1.

Reference:
Patent; MILLENNIUM PHARMACEUTICALS, INC.; WO2006/41773; (2006); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts