Month: November 2020

403-54-3, Adding some certain compound to certain chemical reactions, such as: 403-54-3, name is 3-Fluorobenzonitrile, 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 403-54-3.

General procedure: To an oven-dried 15 mL sealed tube were added 2-aminophenylmethanol 1 (0.425 mmol), benzonitrile 2(0.25 mmol), Ru cat. b (1.94 mg, 1 mol%), and KOtBu (14.02 mg, 0.5equiv) intamyl alcohol (1 mL) under an air atmosphere. The sealedtube was capped and heated at 130C for 2 h. The reaction mixturewas cooled down to room temperature and directly concentratedunder vacuum. The crude mixture was puried by preparative thin-layer-chromatography (petroleum ether/ethyl acetate 20/1) togive the desired product 3 or 4.

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 403-54-3.

Reference:
Article; Wan, Xiao-Min; Liu, Zi-Lin; Liu, Wan-Qing; Cao, Xiao-Niu; Zhu, Xinju; Zhao, Xue-Mei; Song, Bing; Hao, Xin-Qi; Liu, Guoji; Tetrahedron; vol. 75; 18; (2019); p. 2697 – 2705;,
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1080-74-6, name is 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile, 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. 1080-74-6

General procedure: Compound 4 (400 mg, 0.47 mmol) and INCN (458 mg, 2.36 mmol) were dissolved in anhydrous chloroform (CF, 25 mL) and 0.3 mL of pyridine was slowly injected into mixture solution. Thereaction was stirred under a nitrogen atmosphere at 65 C for 12 h. Subsequently, the reaction vessel was cooled to room temperature and extracted with chloroform several times. The extracted organic layer were dried over MgSO4, filtered, and evaporated to obtain a residue. The mixture compound was then purified with column chromatography using chloroform to afford a dark solid.

Statistics shows that 1080-74-6 is playing an increasingly important role. we look forward to future research findings about 2-(3-Oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile.

Reference:
Article; Lee, Seong Lim; Kim, Hee Su; Ha, Jong-Woon; Park, Hea Jung; Hwang, Do-Hoon; Bulletin of the Korean Chemical Society; vol. 41; 2; (2020); p. 143 – 149;,
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17626-40-3, name is 3,4-Diaminobenzonitrile, 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. 17626-40-3

A solution of 1 (557.5 mg, 2.5 mmol), 3, 4-diaminobenzonitrile (332.5 mg, 2.5 mmol), and benzoquinone (270.2 mg, 2.5 mmol) in ethanol (40 mL) was allowed to reflux under nitrogen for overnight. The reaction mixture was distilled off under reduced pressure. The residue was triturated with ether and filtered off to afford 2 in 90%, mp >340 C.’H NMR (DMSO-d6) ; J 7.20 (d, J = 8.4 Hz, 1 H), 7.68 (d, J = 8.4 Hz, 1 H), 7.86-7. 98 (m, 6H), 8.28 (s, 1 H), 8.57 (s, 1H), 12.80 (brs, 1H), 13.65 (brs, 1H). 13C NMR ; No. 158. 4, 153. 9,143. 5,132. 9, 131.0, 129.3, 126.7, 125.7, 119.7, 118.9, 118.1, 112.8, 109.4, 104.5. MS (m/z, rel. int. ); 336 (M+, 100), 307 (25), 280 (5), 164 (10). High resolution calcd. for C21H12N4O ms 336. 10111. Observed 336.10189. Anal. (C21H12N4O-0.25H2O) C, H, N.

Statistics shows that 17626-40-3 is playing an increasingly important role. we look forward to future research findings about 3,4-Diaminobenzonitrile.

Reference:
Patent; UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL; GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.; WO2005/40132; (2005); A1;,
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1558-82-3,Some common heterocyclic compound, 1558-82-3, name is Ethyl N-cyanoacetimidate, molecular formula is C5H8N2O, 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.

Intermediate 33Preparation of N’-cyano-N-(cyanomethyl)-N-methylacetimidamideTo a solution of ethyl N-cyanoacetimidate (1.12 g; 10 mmol) in ethanol (20 mL) was add 2-(methylamino)acetonitrile (0.736 g; 10.5 mmol) and the reaction mixture was stirred at room temperature for 24 h. The volatiles were removed under reduced pressure and the 1.36 g (100%) of the crude white solid were dried and used without further purification. ESI/APCI(+): 137 (M+H).

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

Reference:
Patent; KATHOLIEKE UNIVERSITEIT LEUVEN; US2012/316161; (2012); A1;,
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Some common heterocyclic compound, 453565-55-4, name is 5-Fluoroisophthalonitrile, molecular formula is C8H3FN2, 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. 453565-55-4

Example 15 To a solution of 1-(3-hydroxyphenyl)ethanol (69 mg) in 1-methyl-2-pyrrolidinone under a nitrogen atmosphere was added sodium hydride (60% in oil, 44 mg). The mixture was stirred at 20 C. for 10 minutes then 5-fluoroisophthalonitrile (0.161 g) was added and the mixture heated at 100 C. for 0.5 hour then at 150 C. for a further 0.5 hour. The cooled mixture was diluted (ethyl acetate), washed (water), dried over magnesium sulphate, evaporated and purified by dry column chromatography on silica (eluent dichloromethane/isohexane) to yield 1-(3,5-dicyanophenoxy)-3-[1-(3,5-dicyanophenoxy)ethyl]benzene (Compound 89, 84 mg), NMR (300 MHz, CDCl3) 7.56 (1H, t); 7.45-7.38 (2H, m); 7.32 (2H, d); 7.24 (2H, d); 7.22-7.18 (1H, m); 6.98 (1H, t); 6.92 (1H, dd); 5.29 (1H, quartet); 1.66 (3H, d).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 453565-55-4, its application will become more common.

Reference:
Patent; Cornell, Clive; Cramp, Michael Colin; Gingell, Michael; Westaway, Susan; US2003/181334; (2003); A1;,
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50712-68-0, 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. 50712-68-0, name is 4-Chloro-2-methylbenzonitrile, A new synthetic method of this compound is introduced below.

2-(bromomethyl)-4-chlorobenzonitrileInto a 50-mL round-bottom flask, was placed a mixture of 4-chloro-2-methylbenzonitrile (1 g, 6.60 mmol, 1.00 equiv), CCl4 (15 mL), NBS (1.29 g, 7.25 mmol, 1.10 equiv) and BPO (50 mg, 0.20 mmol, 0.03 equiv). The resulted solution was stirred for 16 h at 80 C. The reaction mixture was cooled to 25 C. Then it was washed with 3¡Á15 mL of water. The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column and eluted with ethyl acetate/ hexane (1:50). This resulted in 0.45 g (30%) of 2-(bromomethyl)-4-chlorobenzonitrile as a light yellow solid. LC-MS (ESI) m/z: Calculated for C8H5BrClN: 228.9. found: 230 [M+H]+.

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; Global Blood Therapeutics, Inc.; Li, Zhe; Xu, Qing; Yu, Chul; Yee, Calvin; Gwaltney,, II, Stephen L.; Metcalf, Brian W.; Richards, Steven; Lardy, Matthew A.; Setti, Lina; Sham, Hing; US2015/315198; (2015); A1;,
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133116-83-3, 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. 133116-83-3 name is 2-Fluoro-6-(trifluoromethyl)benzonitrile, 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.

2-Fluoro-6-(trifluoromethyl)benzonitrile (10 g, 0.053 mol) was warmed at 40C in 200 ml of anhydrous methylamine in an autoclave for 2 days. The excess methylamine was allowed to evaporate and the resulting grey solid was dissolved in 200 ml of methylene chloride together with 4-aminopyridine (0.1 g, 0.001 mol) and triethylamine (3.3 ml, 0.026 mol). To the chilled solution was slowly added ethyl malonyl chloride (8.8 g, 0.060 mol). The solution was stirred for 4 hours and then worked up to give a yellowish syrup. The syrup was dissolved in 100 ml of anhydrous ethanol, and sodium methoxide (5.4 g, 0.10 mol) was added. After 1 hour, the solvent was removed and the residue worked up with methylene chloride and water. The quinoline derivative formed was carefully dried and suspended in 250 ml of chilled anhydrous tetrahydrofuran. Sodium hydride (4 g, 0.125 mol) was slowly added and then methyl iodide (10 ml, 0.15 mol). The mixture was heated under reflux for 6 hours, quenched with water and worked up with diethyl ether. The solvents were removed and the residue (17.3 g) was dissolved in a mixture of ethanol (50 ml) and conc. hydrochloric acid (10 ml). The solution was warmed at 45C overnight, cooled and the precipitate was collected to give 8 g of the title compound, yield 48 %. 1H NMR delta (CDCl3) delta 1.46 (3H, t), 3.68 (3H, s), 4.50 (2H, q), 7.58 (1H, m), 7.71 (2H, m), 15.0(1H, s).

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

Reference:
Patent; Active Biotech AB; EP1095021; (2003); B1;,
Nitrile – Wikipedia,
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19179-31-8, 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 19179-31-8 as follows.

Synthesis of Intermediate (1)(1 )Molecular Weight: 163.17 Molecular Weight: 197.3[00378] In a 3-neck 100 mL round-bottomed flask, 3,5-dimethoxy benzonitrile (10.0 g, 1 eq.), NaSH H20 (9.43 g, 2.0 eq.) and MgCl26H20 (12.43 g, 1.0 eq.) were dissolved in DMF (100 mL, 10 Vol.). The reaction mixture was stirred at room temperature for 2 h. Reaction completion was monitored on TLC using ethyl acetate: n-hexane (2:8)as mobile phase. Reaction mixture was brought to room temperature and quenched into the ice-water slurry (100 mL) and compound was extracted in the ethyl acetate (50 mL x 3). Organic layer was washed with brine solution (50 mL x 3) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 2.5 g of crude compound, yield (20.68 %). Mass/LCMS: 197.0 NMR: Confirmed.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 19179-31-8, and friends who are interested can also refer to it.

Reference:
Patent; KARYOPHARM THERAPEUTICS, INC.; SHECHTER, Sharon; KAUFFMAN, Michael; SANDANYAKA, Vincent, P.; SHACHAM, Sharon; WO2011/109799; (2011); A1;,
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These common heterocyclic compound, 134521-16-7, name is 4,4′-Dicyanobenzhydrol, 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. 134521-16-7

EXAMPLE 1 This example demonstrates a method for preparing bromo-bis-(4-cyanophenyl)-methane. A three-necked round-bottom flask equipped with a mechanical stirrer, a nitrogen inlet and a Dean Stark apparatus was charged with bis-(4-cyanophenyl)-methanol (60 g, 0.256 mole) and toluene (360 ml) and the reaction mixture was heated to 60 C. HBr (48%, 54 ml, 1.8 eq.) was added in one portion and the reaction mixture was refluxed for two hours, during which time water was removed by azeotropic distillation. The reaction mixture was cooled to 70 C., water was added (250 ml), and stirring was maintained for 5 minutes. The two resulting layers were separated, the aqueous phase was washed with toluene (50 ml), and the organic layers were combined and washed with an aqueous solution of 5% potassium carbonate (200 ml), then with water (250 ml). Toluene was distilled off under reduced pressure (about 290 ml) and the solution was cooled to 40 C. Hexane was added (240 ml) and the mixture was cooled to room temperature and stirring was maintained for about 18 hours. The crude solid product was obtained by filtration (70.3 g) in 92% yield, having a purity of 99% (by HPLC).

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 134521-16-7.

Reference:
Patent; CHEMAGIS LTD.; US2007/112202; (2007); A1;,
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Some common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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. 103146-25-4

Oxalate [(+-)-Diol Oxalate Salt] (+-)-Diol compound (VI) (7 g, 0.0205 mol) and oxalic acid dihydrate (2.83 g, 0.0225 ml) were added to isopropyl alcohol (77 ml) and heated the contents to 75-80 C. to obtain a clear solution. The obtained solution was cooled to 10-15 C. and stirred for 2 h to complete the crystallization. The product was filtered, and thereafter dried at 50-60 C. under reduced pressure for 6 h to give 8.6 g of diol oxalate salt (VIa), with HPLC purity of 99.94%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 103146-25-4, its application will become more common.

Reference:
Patent; Kaushik, Vipin Kumar; Mohammed, Umar Khan; Meenakshisunderam, Sivakumaran; US2009/99375; (2009); A1;,
Nitrile – Wikipedia,
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