Author: tianli

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. 1897-52-5, name is 2,6-Difluorobenzonitrile, A new synthetic method of this compound is introduced below., Formula: C7H3F2N

To a suspension of 2,6-difluorobenzonitrile (20.0 g, 144 mmol) andK2CO3 (40.00 g, 289 mmol) in dimethyl sulfoxide (80 mL), morpholine(13.20 g, 152 mmol) was slowly added. The mixture was heated at 90 C for 3 h. After completion of the reaction, as indicated by TLC,the reaction mixture was carefully poured into stirred water (500 mL)and then filtered. The filter cake was washed with water and dried to yield 18.0 g of 2-fluoro-6-morpholinobenzonitrile in 90.0% yield;m.p. 69-70 C (lit.13 69-70 C); IR (KBr, numax/cm-1): 3096, 2972, 2950,2879, 2869, 2226 (CN), 1605, 1567, 1447, 1257, 1230, 1114, 1082, 1058;MS (ESI) m/z (%): 207.3 [M+H]+; Anal. calcd for C11H11FN2O: C,64.07; H, 5.38; N, 13.58; found: C, 63.99; H, 5.42; N, 13.63%.

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:
Article; Ji, Xiao-Hui; Jin, Ling-Xia; Zhao, Cai-Bin; Zheng, Nan; Song, Juan; Ge, Hong-Guang; Liu, Quan; Lu, Jiu-Fu; Journal of Chemical Research; vol. 42; 10; (2018); p. 504 – 507;,
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Application of 19472-74-3, These common heterocyclic compound, 19472-74-3, name is 2-Bromophenylacetonitrile, 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.

General procedure: A flask was equipped with a magnetic stir bar and charged with 1Hpyrrole-2-carbaldehyde (2a; 19.0 mg, 0.2 mmol, 1.0 equiv), 2-bromophenylacetonitrile(1a; 39.2 mg, 0.2 mmol, 1.0 equiv), and K3PO4(63.6 mg, 0.3 mmol, 1.5 equiv). The flask was evacuated and filledwith N2, and then anhydrous DMSO (2.0 mL) was introduced via a syringe.The flask was heated in a 130 C oil bath for 24 h, at which timeTLC analysis [petroleum ether (bp 60-90 C)-EtOAc, 10:1] indicatedcomplete consumption of 2a and 1a. The reaction mixture was cooledto r.t. and added to a sat. solution of NaCl (20 mL) and extracted withEtOAc (3 ¡Á 10 mL). The combined organic layers were dried (Na2SO4)and filtered. The filtrate was concentrated, and the residue was purified by column chromatography on SiO2 [petroleum ether (bp 60-90C)-EtOAc, 10:1 to 30:1] to give 3ad; Yield: 40.5 mg (84%); fluorescent yellow solid; mp 193.7-194.6 C.

Statistics shows that 2-Bromophenylacetonitrile is playing an increasingly important role. we look forward to future research findings about 19472-74-3.

Reference:
Article; Jiang, Zeng-Qiang; Miao, Da-Zhuang; Tong, Yao; Pan, Qiang; Li, Xiao-Tong; Hu, Ren-He; Han, Shi-Qing; Synthesis; vol. 47; 13; (2015); p. 1913 – 1921;,
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Reference of 53312-81-5, 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 53312-81-5 as follows.

A solution of Et3N (0.179 mL, 1.29 mmol) in DMF (1.9 mL) was added to 3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylic acidIl25 mg, 0.428 mmol), HATU (204mg, 0.535 mmol), 4-fluoro-3-methylaniline (107 mg, 0.857 mmol) and stirred overnight. The solution was subjected to column chromatography using a gradient from 10 till 100% EtOAc in heptane. The product fractions were combined and concentrated. Compound 94 (78 mg) was obtained as a white powder after drying in vacuo at 50C.J=4.8 Hz, 1 H), 8.56 (d, J=8.8 Hz, 1 H), 13.13 (br. s., 1 H). Compound 170 (531 mg) was synthesized similarly as described for compound 94 using 3-fluoro-1-methyl-4-[[(1R)-2,2,2- trifluoro-1-methyl-ethyl]sulfamoyl]pyrrole-2-carboxylic acid (601.7 mg 1.89 mmol) instead of 3 -fluoro- 1 -methyl-4- [(3 -methyloxetan-3 -yl)sulfamoyl]pyrrole-2-carboxylic acid and 5 -amino-2-fluorobenzonitrile (531 mg, 3.78 mmol) instead of 4-fluoro-3 -methylaniline and the reaction mixture was stirred overnight at 65C. The column fractions were concentrated and the residue was crystallized by dissolving in 100 mL warm methanol upon addition of water. The crystals were filtered off and dried overnight in vacuo at 50C. Method A: Rt: 1.66 mm mlz: 435 (M-H) Exact mass: 436.06.?H NMR (400 MHz, DMSO-d6) oe ppm 1.18 (d, J=6.8 Hz, 3 H), 3.81 (s, 3 H),3.91 – 4.05 (m, 1 H), 7.50 – 7.59 (m, 2 H), 7.96 (ddd, J=9.2, 5.0, 2.8 Hz, 1 H), 8.17 (dd, J=5.8,2.8 Hz, 1 H), 8.62 (d, J=8.8 Hz, 1 H), 10.36 (s, 1 H). Differential scanning calorimetry: From 30 to 300 C at 10C/mm: peak at 190.99 C.

According to the analysis of related databases, 53312-81-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
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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. 1009-35-4, name is 4-Fluoro-3-nitrobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H3FN2O2

A mixture of 4-fluoro-3-nitrobenzonitrile (5.0 g, 30.1 mmol) and Fe powder (5.05 g, 90.3 mmol) in AcOH (100 mL) was heated at 80¡ã C. for 1 hour under N2. Then the solvent was removed under vacuum and water (200 mL) was added to the residue. The solution was adjusted to pH 6 by addition of Na2CO3?and extracted with DCM (2¡Á200 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated to yield 3-amino-4-fluorobenzonitrile (48), which was used without further purification. MS m/z 137.0 (M+1)+.; To a stirring suspension of imidazo[1,2-a]pyridine-3-carboxylic acid (1) (3.0 g, 18.5 mmol) in anhydrous dichloromethane (50 mL) at 0¡ã C. was added dropwise oxalyl chloride (4.84 mL, 55.5 mmol). Then, three drops of anhydrous DMF was added and the reaction mixture was stirred at room temperature for 15 minutes. The solvent was concentrated and the crude solid was added to a stirring solution of 3-amino-4-fluorobenzonitrile (48) (2.5 g, 18.5 mmol) in anhydrous pyridine (50 mL) at room temperature. The reaction was stirred for 20 minutes and quenched with water (200 mL) with stirring for another 10 minutes. Then the precipitate was filtered and dried in air to yield N-(5-cyano-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (49).?1H NMR (400 MHz, d6-DMSO) delta 10.40 (s, 1H), 9.43 (td, J=1.2, 6.8 Hz, 1H), 8.63 (s, 1H), 8.21 (dd, J=2.0, 7.2 Hz, 1H), 7.78-7.84 (m, 2H), 7.54-7.63 (m, 2H), 7.22 (dt, J=1.2, 6.8, 1H). MS m/z 281.1 (M+1)+.; NH2OH (10 mL, 32.1 mmol) was added in one portion to a stirred suspension of N-(5-cyano-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (49) (3.6 g, 12.85 mmol) in EtOH (100 mL). The resulting suspension was heated at 70¡ã C. for 3 hours and then the solvent was removed to yield N-(2-fluoro-5-(N?-hydroxycarbamimidoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (50).?1H NMR (400 MHz, d6-DMSO) delta 10.21 (s, 1H), 9.70 (s, 1H), 9.45 (td, J=1.2, 7.2 Hz, 1H), 8.61 (s, 1H), 7.95 (dd, J=2.4, 7.6 Hz, 1H), 7.79 (td, J=1.2, 8.8 Hz, 1H), 7.51-7.60 (m, 2H), 7.31-7.37 (m, 1H), 7.19 (dt, J=1.2, 6.8, 1H), 5.88 (s, 2H). MS m/z 314.1 (M+1)+.

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 1009-35-4.

Reference:
Patent; IRM LLC; YEH, Vince; LI, Xiaolin; LIU, Xiaodong; LOREN, Jon; MOLTENI, Valentina; NABAKKA, Juliet; NGUYEN, Bao; PETRASSI, Hank Michael James; US2013/59846; (2013); 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. 3759-28-2, name is 2-(Cyanomethyl)benzonitrile, A new synthetic method of this compound is introduced below., Quality Control of 2-(Cyanomethyl)benzonitrile

To a solution of 2-cyanophenylacetonitrile 26 (300mg, 2.11mmol) and 1, 3, 5-triazine (205.3mg, 2.53mmol) in MeOH (10.6mL) was added 28% NaOMe methanol solution (2.04g, 10.6mmol). The mixture was stirred at ambient temperature for 1h. The reaction mixture was poured into with 10% NH4Cl solution and MeOH. After removing the solvent, EtOAc and H2O was added. After separating EtOAc, the aqueous phase was extracted with EtOAc twice. The combined organics were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was stirred in iPrOH/Heptane. The solid was collected after filtration to give the known amino-isoquinoline 27 (319.1mg, 81.6%) as pale yellow solid. The product was identified with previously reported data.

The synthetic route of 3759-28-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hayashida, Joji; Yoshida, Shinya; Tetrahedron Letters; vol. 59; 43; (2018); p. 3876 – 3879;,
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Synthetic Route of 501-00-8, 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. 501-00-8, name is 2-(3-Fluorophenyl)acetonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To a solution of 11a-c (10 mmol) in anhydrous DMF (15 mL) was added appropriate aryl acetonitriles (12 mmol). After stirring at -10C for about 15 min, 60% NaH (0.48 g, 12 mmol) was added portion wise under a nitrogen atmosphere and maintained at this condition for 1 h. Then, the resulting mixture was warmed slowly to room temperature and continued to react for 12-24 h. After that, additional NaH (0.48 g, 12 mmol) was added and the air was introduced, the mixture was stirred at room temperature for another 12-24 h to yield 13a-q. Without further purification, 13a-q were hydrolyzed with 30% aqueous sodium hydroxide at room temperature for 4 h, and afterwards, the mixture was poured into 300 ml H2O and neutralized with 3N HCl. The precipitate was collected and purified by column chromatography on silica gel (hexane: EtOAc=8:1-1:1) to afford the target compounds 7a-q.

The synthetic route of 2-(3-Fluorophenyl)acetonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wu, Hai-Qiu; Yan, Zi-Hong; Chen, Wen-Xue; He, Qiu-Qin; Chen, Fen-Er; De Clercq, Erik; Balzarini, Jan; Daelemans, Dirk; Pannecouque, Christophe; Bioorganic and Medicinal Chemistry; vol. 21; 21; (2013); p. 6477 – 6483;,
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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. 1835-65-0, name is 3,4,5,6-Tetrafluorophthalonitrile, A new synthetic method of this compound is introduced below., HPLC of Formula: C8F4N2

Example 1; Synthesis of hexadecafluorovanadylphthalocyanine; Into a separable flask of glass provided with a stirrer, a thermometer, a water separation tube, and a cooling tube and having an inner volume of 300 ml, a nitrogen gas was introduced at a rate of 500 ml/min for 10 minutes to replace the interior of the reaction vessel with the nitrogen gas. Then, the reaction vessel was charged with 30 gr (0.15 mol) of tetrafluorophthalonitrile, 58.6 gr (0.45 mol) of n-octanol, and 6.9 gr (0.0438 mol) of vanadium trichloride (produced by Sinko Kagaku K.K.). Again, a nitrogen gas was introduced at a rate of 500 ml/min for 10 minutes into the reaction vessel to replace the interior thereof with the nitrogen gas. When the oxygen concentration in the reaction vessel was determined with an oxygen concentration meter, it was found to be 1.8 vol percent. Under the condition of continued stirring, the reaction mixture in the reaction vessel was exposed to a current of nitrogen gas at a flow rate of 30 ml/min and heated. The linear speed of the gas at the inlet part (the connecting part between the reaction vessel and the cooling tube) was 0.6 cm/sec and the oxygen concentration in the reaction vessel was measured with an oxygen concentration meter to be found to be 1.8 vol percent. The temperature was elevated to 150¡ã C. over two hours, then the reaction was further continued for three hours, and the reaction vessel was left cooling to normal room temperature. In the meanwhile, the flow of the nitrogen gas was continued. The conversion of tetrafluorophthalonitrile was determined by liquid chromatography, to find to be 99.2percent. The slurry resulting from the cyclization was filtered to separate a solid component. The solid component was washed with 300 gr of benzonitrile, then washed with 100 gr of methanol, and dried under a reduced pressure at 150¡ã C. for 12 hours. The weight of the target product, hexadecafluorovanadyphthalocyanine, as calculated from the weight after drying, was 28.1 gr (yield: 86.4 mol percent).; Comparative Example 4; When the reaction was performed by following the procedure of Example 1 while omitting the replacement with a nitrogen gas prior to the reaction and the introduction of a nitrogen gas during the course of the reaction, and supplying air at a flow rate of 30 ml/min to the reaction vessel, the weight of hexadecafluorovanadyl phthalocyanine was found to be 12.5 gr (yield: 38.5 mol percent). When the oxygen concentration in the reaction vessel was determined at this time with an oxygen concentration meter, it was found to be 20.3 vol percent.

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; Hirota, Kouichi; Hashimoto, Yukihide; Masuda, Kiyoshi; Kitao, Masunori; US2005/203293; (2005); A1;,
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Adding a certain compound to certain chemical reactions, such as: 194853-86-6, name is 4-Fluoro-2-(trifluoromethyl)benzonitrile, 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 194853-86-6, Computed Properties of C8H3F4N

Reference Example 44 4-(4-formyl-2-methoxyphenoxy)-2-(trifluoromethyl)benzonitrile; [Show Image] To a solution (15 mL) of 4-hydroxy-3-methoxybenzaldehyde (1.00 g) in dimethyl sulfoxide were added lithium carbonate (721 mg) and 4-fluoro-2-(trifluoromethyl)benzonitrile (1.49 g), and the mixture was stirred at 100C for 2 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-heptane to give the title compound as a colorless solid (yield: 1.91 g, 92%). 1H-NMR (DMSO-d6, 300 MHz):delta3.84 (3H, s), 7.26 (1H, dd, J = 8.7, 2.5 Hz), 7.48 (1H, d, J = 7.9 Hz), 7.57 (1H, d, J = 2.5 Hz), 7.67 (1H, dd, J = 7.9, 1.7 Hz), 7.72 (1H, d, J = 1.7 Hz), 8.12 (1H, d, J = 8.7 Hz), 10.02 (1H, s).

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; Takeda Pharmaceutical Company Limited; EP2450352; (2012); A1;,
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Application of 116332-64-0, The chemical industry reduces the impact on the environment during synthesis 116332-64-0, name is 4-Cyano-N-methoxy-N-methylbenzamide, I believe this compound will play a more active role in future production and life.

A solution of n-butyllithium (2.5 M in hexanes, 0.8 mL, 2.0 mmol) was added dropwise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-((4-(trifluoromethyl)piperidin-1-yl)methyl)quinoline (0.964 g, 2.20 mmol, Intermediate 40) in dry deoxygenated THF (14 mL) at -78 C. After 2 minutes, a solution of 4-cyano-N-methoxy-N-methylbenzamide (0.13 g, 0.50 mmol, Intermediate 78: step a) in dry THF (4 mL) was added dropwise by syringe. An additional 2 mL of THF was used to complete the quantitative addition. After 2 hours of stirring at -78 C., the reaction was quenched with saturated aqueous ammonium chloride solution and the mixture was partitioned between water and EtOAc. The layers were separated and the aqueous phase was further extracted with EtOAc and washed with saturated aqueous NaCl solution. The organic phase was dried (MgSO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography to provide the title compound.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 4-Cyano-N-methoxy-N-methylbenzamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JOHNSON & JOHNSON; LEONARD, KRISTI A.; BARBAY, KENT; EDWARDS, JAMES P.; KREUTTER, KEVIN D.; KUMMER, DAVID A.; MAHAROOF, UMAR; NISHIMURA, RACHEL; URBANSKI, MAUD; VENKATESAN, HARIHARAN; WANG, AIHUA; WOLIN, RONALD L.; WOODS, CRAIG R.; FOURIE, ANNE; XUE, XIAOHUA; CUMMINGS, MAXWELL D.; MCCLURE, KELLY; TANIS, VIRGINIA; US2015/111870; (2015); 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. 26391-06-0, name is 2-Cyano-N,N-diethylacetamide, A new synthetic method of this compound is introduced below., Safety of 2-Cyano-N,N-diethylacetamide

A mixture of 3-formyl-5-(2-hydroxyethyl)benzonitrile (315 mg, 1.8 mmol), 2-cyano- (1007) N,N-diethylacetamide (252 mg, 1.8 mmol) and ammonium acetate (693 mg, 9mmol) in methanol (10 mL) was stirred at reflux temperature for 4 h. Cooled and concentrated. The residue was diluted with EtOAc (50 mL), and washed with water (50 mL) and brine (50 mL). The organic layers were dried over Na2S04 and concentrated. The crude residue was purified by silica gel chromatography to afford the title compound as a yellow gum (210 mg, 49 %).

The synthetic route of 26391-06-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PRINCIPIA BIOPHARMA INC.; LOU, Yan; OWENS, Timothy Duncan; BRAMELD, Kenneth Albert; GOLDSTEIN, David Michael; (171 pag.)WO2019/99576; (2019); A1;,
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