Author: Jessica.F

Synthetic Route of 42872-74-2,Some common heterocyclic compound, 42872-74-2, name is 3-Bromo-4-methylbenzonitrile, molecular formula is C8H6BrN, 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.

[0332] 2-Fluoro-5-iodobenzonitrile (0.41 mg, 1.7 mmol), triphenylphosphine (0.088 g, 0.33 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.076 mg, 0.084 mmol) were dissolved in THF (15 ml) and flushed with nitrogen. Themixture was treated with 1-(4-ethynyl-4-hydroxypiperidin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone (520 mg, 1.7mmol) followed by tetrabutylammonium fluoride solution in THF (1.0 M, 3.3 ml, 3.3 mmol), sealed and placed in an oilbath at 60 C for 3 h. The mixture was cooled, diluted with water and ethyl acetate, and the layers separated. After theaqueous was extracted with additional ethyl acetate (2x), the combined organics were washed successively with water(2x) and brine, dried (Na2SO4) and concentrated. The resulting residue was purified by MPLC (eluent gradient 10->50%EtOAc:hex.) to provide 2-fluoro-5-[(4-hydroxy-1-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperidin-4-yl)ethynyl]benzonitrile:_[0361] 3-[(4-Hydroxy-1-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperidin-4-yl)ethynyl]-4-methylbenzonitrile was preparedin a similar fashion to that described for the synthesis of EXAMPLE 10 starting from 1-(4-ethynyl-4-hydroxypiperidin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone and 3-bromo-4-methylbenzonitrile. 1H NMR (500 MHz, CDCl3, delta in ppm): 9.02(s, 1H), 7.72 (d, J = 8.5 Hz, 2H), 7.61 (s, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.36 (m, 2H), 4.06 (m, 1H), 3.89 (s, 2H), 3.76 (m,1H), 3.59 (m, 1H), 3.35 (m, 1H), 2.51 (s, 3H), 2.08 (m, 2H), 1.91 (m, 2H).

The synthetic route of 42872-74-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck Sharp & Dohme Corp.; WALSH, Shawn; PASTERNAK, Alexander; CATO, Brian; FINKE, Paul, E.; FRIE, Jessica; FU, Qinghong; KIM, Dooseop; PIO, Barbara; SHAHRIPOUR, Aurash; SHI, Zhi-Cai; TANG, Haifeng; (136 pag.)EP2755656; (2016); B1;,
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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. 1187-42-4, name is Diaminomaleonitrile, A new synthetic method of this compound is introduced below., Quality Control of Diaminomaleonitrile

Example 1-1; Methanol, in an amount of 216 mL, was placed in a four-necked flask with a volume of 500 mL, and 108.1 g (purity: 98.7percent, 0.987 mol) of DAMN and 116.73 g (1.100 mol) of trimethyl orthoformate were added thereto. p-Toluenesulfonic acid, monohydrate, in an amount of 190 mg, was added to the aforementioned mixture, and the reaction mixture was stirred while maintaining the temperature at 65¡ãC. 45 minutes after stirring was started, crystals of MMD were precipitated, and completion of the reaction was suggested. After the reaction mixture was stirred for 1.5 hours, the reaction mixture was cooled to 5¡ãC. The crystals were filtered and washed with 100 mL of cooled methanol, followed by drying. Thereby, 118.56 g (0.852 mol, yield = 80percent) of methyl N-(2-amino-1,2-dicyanovinyl)formimidate (MMD) was obtained.

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; Nippon Soda Co., Ltd.; EP2138480; (2009); A1;,
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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. name: 2-(4-Aminophenyl)-2-methylpropanenitrile

1. Preparation of methyl 6-chloro-4-(4-(2-(cyanopropan-2-yl)phenylamino) -1,5-naphthyridine-3-carboxylate Ethyl 4,6-dichloro-1,5-naphthyridine-3-carboxylate (5.0g, 18.4mmol) and 2-(4-aminophenyl)-2-methylpropanenitrile (2.96g, 18.5mmol) were dissolved in 1,4-dioxane (80mL). The reaction was conducted with stirring under reflux for 4hrs. The reaction mixture was cooled, and concentrated in a reduced pressure. The resulting solid was dissolved with dichlormethane, successively washed with saturated aqueous sodium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated in a reduced pressure to produce 6.54g of the title compound as a pale-yellow solid in a yield of 90.2%.

The synthetic route of 115279-57-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Xuanzhu Pharma Co., Ltd.; WU, Frank; ZHANG, Yan; EP2719697; (2014); A1;,
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16532-79-9, name is 4-Bromophenylacetonitrile, 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. Safety of 4-Bromophenylacetonitrile

To a solution of (4-bromo-phenyl)-acetonitrile (1 g, 5.10 mmol) in DMF (10 mL) is added sodium hydride (0.408 g, 10.20 mmol, 60% in mineral oil) at 0 C. The reaction mixture is stirred at 0 C. for 15 minutes and then methyl iodide (0.69 mL, 11.22 mmol) is added at 0 C. The reaction mixture is stirred at room temperature for overnight. The reaction mixture is quenched with aqueous ammonium chloride solution (5 mL) and extracted with EtOAc (2*20 mL). The combined organic extracts are washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered, and evaporated. The crude material is purified over silica gel column chromatography (combiflash) eluting with 5-10% EtOAc in hexanes to give an off white solid (0.9 g, 78%). 1H NMR (400 MHz, CDCl3) delta 7.51 (d, J=8.4 Hz, 1H), 7.34 (d, J=8.4 Hz, 1H), 1.77 (s, 3H).

The synthetic route of 16532-79-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; Hamdouchi, Chafiq; Maiti, Pranab; Miller, Anne Reifel; (41 pag.)US2016/333005; (2016); A1;,
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Application of 15666-97-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 15666-97-4 name is Octyl 2-cyanoacetate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Preparation of aryl-bis-(2-cyano-3-hydroxy-acrylic acid) ester (102): R = N-OCTYL, I-OCTYL (102) A 1.6 m solution MMOL of n-BuLi in hexane is added at-10C to a solution of 1 mmol diiso- propylamine in THFabs (6 ML/ML DIISOPROPYLAMINE). The mixture is stirred for 15 min. and than cooled down to-78C. After that the solution of 0.5 mmol of the corresponding cyano acetate is added in THF (1 MI/ g cyanoacetate) at this temperature initially, additionally stirred for 15 min and than the SOLU- tion of 0.5 mmol of the acid chloride is added in THF (2 ML/G acid chloride). After stirring of 45 min AT-78C the reaction mixture is quenched at this temperature with 15 % HCI und warmed up to room temperature over night.

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

Reference:
Patent; CIBA SPECIALTY CHEMICALS HOLDING INC.; WO2005/12235; (2005); A1;,
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Related Products 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;,
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Reference of 1897-52-5, These common heterocyclic compound, 1897-52-5, name is 2,6-Difluorobenzonitrile, 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.

Add 0.11 mol (7.65 g) to a 250 mL reaction flask.Hydroxylamine hydrochloride,50g of ethyl acetate as a solvent,Then add 0.11 mol of triethylamine (11.11g)And 0.1 mol (13.9 g) of 2,6-difluorobenzonitrile,Stir,Heating at 80 C for 4 h,TLC tracking reaction is complete,cool down,Filtering,The filtrate was evaporated to remove EA.cool down,Obtained white solid compound II 14.62g,The yield was 85%.

Statistics shows that 2,6-Difluorobenzonitrile is playing an increasingly important role. we look forward to future research findings about 1897-52-5.

Reference:
Patent; Qingdao University of Science and Technology; Xu Liangzhong; Peng Zhuang; Cui Huanqi; Sun Jianxin; Wang Minghui; (8 pag.)CN109320506; (2019); A;,
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Electric Literature of 57418-97-0, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 57418-97-0 name is 4-Bromo-3-chlorobenzonitrile, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

3-chloro-4-bromobenzonitrile (300 mg, 1.39 mmol, 1.0 equiv), o-tolylboronic acid(189 mg, 1.39 mmol, 1.0 equiv), Pd(PPh3)4 (80 mg, 0.07 mmol, 0.05 equiv) and K2CO3 (383 mg, 2.77 mmol, 2.0 equiv) were weighed into a microwave tube and solvated with DME (3.0 mL) and H2O (1.0 mL). The reaction mixture was degassed by bubbling nitrogen through the solution for 5 minutes and then heated to 100 C under microwave irradiation for 2 hours. The reaction was allowed to cool to room temperature, filtered through celite washing with Et2O and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2/H2O and extracted three times with CH2Cl2. The combined organic extracts were washed with a saturated aqueous solution of NaCl, dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 1:9 EtOAc:pet ether) to provide the title compound as a clear oil (300 mg, 1.32 mmol, 95%):

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-3-chlorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Article; Brear, Paul; North, Andrew; Iegre, Jessica; Hadje Georgiou, Kathy; Lubin, Alexandra; Carro, Laura; Green, William; Sore, Hannah F.; Hyvoenen, Marko; Spring, David R.; Bioorganic and Medicinal Chemistry; vol. 26; 11; (2018); p. 3016 – 3020;,
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Electric Literature of 179897-89-3,Some common heterocyclic compound, 179897-89-3, name is 5-Bromo-2-fluorobenzonitrile, molecular formula is C7H3BrFN, 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.

5-Bromo-2-(2,2-dimethyl-butoxy)benzonitrile; Sodium hydride (60% oily) (2.0 g, 50.0 mmol) was gradually added to a solution of 5-bromo-2-fluorobenzonitrile (5.0 g, 25.0 mmol) and 2,2-dimethylbutan-1-ol (5.1 g, 50.0 mmol) in anhydrous DMF (100 mL) at 0C. After stirring at room temperature for 15 hours, the reaction mixture was poured into ice water followed by extracting with ethyl acetate. The organic layer was washed with a saturated saline solution and then dried. The residue prepared by evaporation of the solvent was purified by silica gel column chromatography (hexane/ethyl acetate = 50/1) to give the title compound (6.2 g, 88%) as an oily product.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-2-fluorobenzonitrile, its application will become more common.

Reference:
Patent; Nippon Zoki Pharmaceutical Co., Ltd.; EP2128136; (2009); A1;,
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Reference of 4426-11-3, 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. 4426-11-3, name is Cyclobutanecarbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

1 -[4-(trifluoromethyl)pyridin-2-yl]cyclobutanecarbonitrile[194] 2-Fluoro-4-(trifluoromethyl)pyridine (0.731 mL, 6 mmol) and cyclobutane- carbonitrile (0.841 mL, 9.00 mmol) were dissolved in toluene (10 mL). 0.5M KHMDS (18.00 mL, 9.00 mmol) in toluene was added, and the reaction stirred at ambient temperature for 3 days. The reaction mixture was quenched with water and extracted three times with diethyl ether. The combined organic layers were washed with brine, dried with MgS04, filtered, and concentrated. The residue was chromatographed on an AnaLogix SF25-60g column and eluted with 10% EtOAc in hexanes to give Example 116A (0.88 g, 3.89 mmol, 64.8% yield). MS (DCI+): m/z 227.2 (M+H), 244.1 (M+NH4). XH NMR (300 MHz, DMSO-d6) ? 8.93 (d, J= 5.0 Hz, 1H), 7.96 – 7.90 (m, 1H), 7.82 (ddd, J= 5.1, 1.5, 0.7 Hz, 1H), 2.90 – 2.68 (m, 4H), 2.35 – 2.21 (m, 1H), 2.13 – 2.00 (m, 1H).

The chemical industry reduces the impact on the environment during synthesis Cyclobutanecarbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ABBVIE INC.; BAYBURT, Erol K.; CLAPHAM, Bruce; COX, Phil B.; DAANEN, Jerome F.; GOMTSYAN, Arthur; KORT, Michael E.; KYM, Philip R.; VOIGHT, Eric A.; SCHMIDT, Robert G.; DART, Michael J.; GFESSER, Gregory; WO2013/62966; (2013); A2;,
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