Tag: M.W=100-200

Application of 185147-08-4, A common heterocyclic compound, 185147-08-4, name is 4-Fluoro-3-methylbenzonitrile, molecular formula is C8H6FN, 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.

Example 804-{3-Isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}-3-methylbenzamide (80)4-Fluoro-3-methylbenzonitrile (0.077 g) and cesium carbonate (0.203 g) were added to a solution of compound (6c) (0.150 g) in DMF (1.73 mL), followed by stirring at 80¡ã C. for 18 hr. The reaction solution was distributed between ethyl acetate and water. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled away, and the residue was purified by neutral silica gel column chromatography (hexane/ethyl acetate) to obtain 4-{3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}-3-methylbenzonitrile (0.154 g, 73percent). This 4-{3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}-3-methylbenzonitrile was dissolved in DMSO (5.0 mL) and ethanol (5.0 mL). A 4 N aqueous sodium hydroxide solution (0.195 mL) and a 30percent hydrogen peroxide solution (0.088 mL) were added to the resulting solution, followed by stirring at room temperature for 30 min. Water was added to the reaction solution, and the precipitate was collected by filtration, washed with diethyl ether, and dried under reduced pressure to obtain compound (80) (0.135 g, 83percent) as a white solid.1H-NMR (DMSO-d6) delta: 9.88 (1H, d, J=2.20 Hz), 9.43 (1H, d, J=2.20 Hz), 9.35 (1H, d, J=4.63 Hz), 8.87 (2H, t, J=9.03 Hz), 8.81 (1H, brs), 8.70 (1H, d, J=1.46 Hz), 8.63-8.59 (2H, m), 8.46 (1H, td, J=7.56, 0.73 Hz), 8.30 (1H, d, J=8.05 Hz), 8.20 (1H, brs), 8.09 (1H, d, J=4.63 Hz), 3.72 (1H, tt, J=6.83, 6.83 Hz), 2.94 (3H, s), 1.76 (6H, d, J=6.83 Hz); LRMS (ESI) m/z 422 [M+H]+.

The synthetic route of 185147-08-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAIHO PHARMACEUTICAL CO., LTD.; US2012/108589; (2012); A1;,
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Application of 7357-70-2, A common heterocyclic compound, 7357-70-2, name is 2-Cyanothioacetamide, molecular formula is C3H4N2S, 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.

2-(4-phenylthiazol-2-yl)acetonitrile A mixture of 2-bromoacetophenone (1 .0 g, 5 mmol) and 2- cyanothioacetamide (0.5 g, 10 mmol) in ethanol (25 mL) was heated to 80C for 4 h. The reaction mixture was cooled to room temperature and poured into an aqueous ammonia solution (final pH was >7). The mixture was then extracted with ethyl acetate (100 mL x 3) and the organic layers were washed with H2O and brine. The organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrate in vacuo. The crude product was purified by flash column chromatography, eluting with 0-30% ethyl acetate and petroleum benzene, afforded 2-(4-phenylthiazol-2-yl)acetonitrile (0.69 g, yield 70%) as a yellow solid.

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; MONASH UNIVERSITY; THE UNIVERSITY OF WESTERN AUSTRALIA; BAELL, Jonathan; PIGGOTT, Matthew; RUSSELL, Stephanie; TOYNTON, Arthur; RAHMANI, Raphael; FERRINS, Lori; NGUYEN, Nghi; (178 pag.)WO2015/172196; (2015); A1;,
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Synthetic Route of 19853-10-2, 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. 19853-10-2 name is 2-([1,1′-Biphenyl]-2-yl)acetonitrile, 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.

A 1M solution of hydroxylamine hydrochloride in MeOH (15 ml) and 1M KOH solution in MeOH (15 ml) was combined at 0 C. After 10 minutes, the salt was removed by filtration and the filtrate was directly added to a flask containing 2-(biphenyl-2-yl)acetonitrile (0.50 g, 2.58 mmol) and was heated at 60 C. overnight. The cooled mixture was evaporated to dryness under reduced pressure and the residue was dissolve in EtOAc, washed with water, and brine, dried (MgSO4) and evaporated to dryness. The residue was dissolved in chloroform (10 ml) and treated with dimethyl but-2-ynedioate (0.403 g, 2.84 mmol). The mixture was stirred at 60 C. for 1 h and then evaporated to dryness. The residue was diluted with xylenes (10 ml) and heated at 130 C. for 90 min. The cooled filtrate was filtered, triturated with EtOAc and dried under vacuum to give the title product as an off-white solid (0.161 g; 18%). LCMS: m/z=337 (MH+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-([1,1′-Biphenyl]-2-yl)acetonitrile, and friends who are interested can also refer to it.

Reference:
Patent; SAVIRA PHARMACEUTICALS GMBH; EUROPEAN MOLECULAR BIOLOGY LABORATORY; F. HOFFMANN-LA ROCHE AG; BUSCHMANN, Helmut; WOLKERSTORFER, Andrea; SZOLAR, Oliver; HANDLER, Norbert; CUSACK, Stephen; SMITH, Mark; SO, Sung-Sau; US2014/38990; (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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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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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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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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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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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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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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