Month: June 2021

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. 17354-04-0, name is 2-(4,5-Dimethoxy-2-nitrophenyl)acetonitrile, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-(4,5-Dimethoxy-2-nitrophenyl)acetonitrile

General procedure: Piperidine (0.03 ml, 5 mol %) was added to a warm solution of the appropriate salicylaldehyde 5 (5 mmol) and 2-(4,5-dimethoxy-2-nitrophenyl)acetonitrile (1.12 g, 5 mmol) in EtOH (10 ml). The resulting solution was refluxed with stirring for 5 h. The mixture was treated with a solution of concentrated H2SO4 (0.55 ml) in EtOH (2 ml) and refluxed with stirring for 2 h. The obtained precipitate was filtered, washed with EtOH (10 ml), hot H2O (40 ml) and finally with EtOH (10 ml), and dried at 100 C.

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; Irgashev, Roman A.; Karmatsky, Arseny A.; Slepukhin, Pavel A.; Rusinov, Gennady L.; Charushin, Valery N.; Tetrahedron Letters; vol. 54; 42; (2013); p. 5734 – 5738;,
Nitrile – Wikipedia,
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Reference of 154607-01-9,Some common heterocyclic compound, 154607-01-9, name is 4-Bromo-2-chlorobenzonitrile, molecular formula is C7H3BrClN, 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.

1-(Benzo[d][1,3]dioxol-5-yl)-N-(4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxamide (0.084 g, 0.20 mmol), 4-bromo-2-chlorobenzonitrile (0.043 g, 0.20 mmol), aqueous potassium carbonate (520 muL, 1M), FibreCat 1007 (7 mg), and DMF (1 mL) were combined. The mixture was heated at 80 C. for 18 hours. After cooling, the mixture was filtered and purified by preparative HPLC to provide 1-(benzo[d][1,3]dioxol-5-yl)-N-(3′-chloro-4′-cyano-6-methylbiphenyl-3-yl)cyclopropanecarboxamide.

The synthetic route of 154607-01-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Vertex Pharmaceuticals Incorporated; Van Goor, Fredrick F.; Burton, William Lawrence; US2015/231142; (2015); A1;,
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Reference of 7357-70-2,Some common heterocyclic compound, 7357-70-2, name is 2-Cyanothioacetamide, molecular formula is C3H4N2S, 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-(Bis(methylthio)methylene)malononitrile (10 g, 58.7 mmol) and cyanothioacetamide (7.06 g, 70.5 mmol) were added to a round-bottom flask and dissolved in N,N-dimethylformamide (21 mL). Triethylamine (16.37 mL, 117 mmol) was added dropwise at room temperature and the mixture was stirred for 18 hours. The reaction mixture was added to 300 mL of 3 N hydrochloric acid. The resulting precipitate was filtered off, washed with water and dried with suction to afford 2-amino-6-mercapto-4-(methylthio)pyridine-3,5-dicarbonitrile (13.5 g, 54.7 mmol, 93% yield). LCMS m/z = 222.9 [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 2-Cyanothioacetamide, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ADAMS, Nicholas David; BENOWITZ, Andrew B.; RUEDA BENEDE, Maria Lourdes; EVANS, Karen Anderson; FOSBENNER, David T.; KING, Bryan Wayne; LI, Mei; MILLER, William Henry; REIF, Alexander Joseph; ROMERIL, Stuart Paul; SCHMIDT, Stanley J.; WIGGALL, Kenneth; (1283 pag.)WO2017/216726; (2017); A1;,
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Reference of 14618-78-1, These common heterocyclic compound, 14618-78-1, name is 4,4-Dimethoxybutanenitrile, 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.

SYNTHESIS EXAMPLE 4 Production of methyl 4,5,7-trichloroindole-3-acetate: 10.0 Grams (0.047 mole) of 2,4,5-trichlorophenylhydrazine, 9.2 g (0.07 mole) of beta-cyanopropionaldehyde dimethylacetal and 7.1 g (0.052 mole) of zinc chloride were mixed and then heated in a nitrogen stream at 140 C. for 2 hours. The reaction mixture was cooled to room temperature and dissolved in an acetic acid-water (2:1) solution, and the resulting solution was extracted with ethyl acetate. The ethyl acetate phase was washed with a saturated aqueous sodium bicarbonate solution, water and then a saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate. The ethyl acetate was removed by distillation under reduced pressure to obtain a black oily substance, which was then purified by a silica gel column chromatography to obtained 0.86 g of the desired compound represented by the formula: STR15 The analysis result of NMR of this compound is shown below. 1 H NMR (200 MHz) (CD3)2 CO, TMS) ppm: 7.48 (1H, s).. C2 –H 7.34 (1H, s).. C6 –H 3.99 (2H, s).. CH2 — 3.66 (3H, s).. OCH3 MS (75 ev) (relative intensity, %) m/z 295 (M+ +4, 10), 293 (M+ +2, 23), 291 (M+, 24), 260 (6), 259 (5), 258 (7), 236 (30), 234 (91), 232 (100), 199 (7), 198 (9), 197 (11), 162 (12), 161 (13), 118 (7), 116 (8), 97 (9), 98 (9).

The synthetic route of 14618-78-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nippon Kayaku Kabushiki Kaisha; US4806143; (1989); A;,
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Application of 16588-02-6, 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. 16588-02-6 name is 2-Chloro-5-nitrobenzonitrile, 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.

Reference Example 1 1-(2,6-Dichlorophenyl)-2-oxo-3,4-dihydro-6-(4-fluorophenyl)thioquinazolinea) 2-(2,6-dichlorophenylamino)-5-nitrobenzonitrile 2,6-Dichloroaniline (2.84 g, 17.5 mmol) was dissolved in DMSO (5 mL) and 60% NaH (0.60 g, 15 mmol) was added. The mixture was stirred 30 min and then 2-chloro-5-nitrobenzonitrile (0.91 g, 5.0 mmol) in DMSO (5 mL) was added. The reaction darkened and warmed to 50. After cooling to 23 the reaction was diluted with EtOAc (200 mL) and washed with H2O (3X), satd. aq. NaCl, and dried (Na2SO4), and concentrated to afford 1.45 g (94%) of the title compound as an ivory colored powder. 1H NMR (400) MHz, delta: 8.49 (finely split doublet, 1), 8.20 (dd, 1), 7.51 (d,2), 7.34 (d, 2), 6.41 (d,1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-5-nitrobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; SmithKline Beecham Corporation; EP1233951; (2005); B1;,
Nitrile – Wikipedia,
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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. 950596-58-4, name is 2-Amino-4,5-bis(2-methoxyethoxy)benzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C13H18N2O4

(12.2 g, 50 mmol) (E)-N,N’-bis(3-ethynylphenyl)methyl ether (Compound B) and (13.3 g, 50 mmol) 2-Amino-4,5-bis(2-methoxyethoxy)benzonitrile (Compound C3), 0.5 g of p-toluenesulfonic acid was added to 50 mL of toluene,After heating to 110 C in an oil bath for 5 h, after TLC monitoring reaction, after cooling to room temperature, concentrated, add ice water and stir for 1 h.The brown solid product erlotinib 17.34 g was obtained in a yield of 88.2%, HPLC: 99.24%.

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 950596-58-4.

Reference:
Patent; Yancheng Normal College; Nanjing University Of Technology Dafeng Ocean Industrial Institute; Sun Yaquan; Chen Zhiyuan; Gu Huiwen; Zhang Lijie; Yang Kang; Zong Chaoyang; (11 pag.)CN108503596; (2018); A;,
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Application of 16588-02-6, A common heterocyclic compound, 16588-02-6, name is 2-Chloro-5-nitrobenzonitrile, molecular formula is C7H3ClN2O2, 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.

4-chloro-3-cyanonitrobenzene (600 mg, 1 eq, 3.29 mmol) and DMF (5 mL) were added sequentially to a 100 mL round bottom flask , the flask was sealed with a rubber stopper and stirred the reaction under ice-water bath. Vacuum pumping then recharging N2 , repeat the cycle for 3 times and after stirring the reaction for 10min, the DMF solution of sodium methoxide was slowly injected into the sealed reaction flask through the syringe. After 1h of reaction, the reaction was completed and was stopped. After adding 100 mL of ethyl acetate for dilution, it was washed oncewith the saturated ammonium chloride aqueous solution and saturated aqueous sodium chloride solution. The aqueous phase was again washed with ethyl acetate and the combined organic phase was dried over anhydrous sodium sulfate for 30 min. The mixture was filtered , concentrated then separated by Silica gel column chromatography (PE : EA =5:1) to give a product of 440 mg of product as a White crystalline solid (compound 6) in 75% yield .

The synthetic route of 16588-02-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chinese Academy Of Sciences Shanghai Pharmaceutical Institute; Long Yaqiu; Xu Zhongliang; Wang Heyao; Cai Mengxin; (31 pag.)CN106892871; (2017); A;,
Nitrile – Wikipedia,
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These common heterocyclic compound, 874-97-5, name is 3-Cyanobenzyl alcohol, 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. category: nitriles-buliding-blocks

After 3-(hydroxymethyl)benzonitrile (1.33 g, 10 mmol) was dissolved in dimethylformamide (18 mL), triphenylphosphine (3.14 g, 12 mmol) and imidazole (0.82 g, 12 mmol) were added thereto, and the mixture was cooled to -20C. Iodine (2.79 g, 11 mmol) was added dividing in 5 portions thereto, and the result was stirred for 2 hours at -10C. A 5% aqueous ammonium chloride solution (60 mL) was added to the reaction solution, and the result was extracted with a diethyl ether/ethyl acetate=1/1 solution (60 mLx2). The organic layers were combined, washed with a 1% aqueous sodium thiosulfate solution to remove excess iodine, washed with salted water, dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was separated and purified using silica gel column chromatography (ethyl acetate/normal-hexane=1/9) to give a target compound (1.9 g, 78%) in a white powder state. 1H-NMR (300 MHz, CDCl3) delta 4.41 (s, 2H), 7.2-7.66 (m, 4H); MS (EI, m/e)=243 (M+).

The synthetic route of 3-Cyanobenzyl alcohol has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Korea Research Institute of Chemical Technology; SON, Jong Chan; KIM, Bong Jin; KIM, Jae Hak; LEE, Ill Young; YUN, Chang Soo; LEE, Sang Ho; LEE, Chong Kgo; (98 pag.)EP2781519; (2014); 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 2973-50-4 as follows. Computed Properties of C8H8N2

(2) (2-Aminophenyl)acetonitrile (1.34 g) was dissolved in THF (10 mL), and concentrated hydrochloric acid was added, followed by heating under reflux for 2 hours. The solvent was evaporated, and ethanol (5 mL) and diisopropyl ether (15 mL) were added to suspend the concentrated residue. The crystals were recovered by filtration to obtain 2-imino-2,3-dihydro-1H-indole monohydrochloride (1.42 g).1H NMR (DMSO) delta: 12.46 (s,1H) 10.25 (s,1H), 10.00 (s,1H), 7.42-7.11 (m,4H), 4.18 (s,2H)

According to the analysis of related databases, 2973-50-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP1367058; (2003); 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. 41963-20-6, name is 4-Bromo-3-methylbenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C8H6BrN

Preparations 27-31 are prepared essentially as described for Preparation 26 using the appropriate boronic acid and l-(3-bromo-pyridin-2-yl)-piperazine.Preparation 32: 3-Methyl-4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-benzonitrile Stir together 4-bromo-3-methylbenzonitrile (5.20 mmol, 1.02 g), bis(pinacolato) diboron (5.62 mmol, 1.43 g), potassium acetate (15.6 mmol, 1.53 g), and palladium acetate (0.16 mmol, 40 mg) in dry N,N-dimethylformamide (20 mL). Purge the reaction for 30 min. then heat to 85 0C overnight. Partition between water (100 mL) and ethyl acetate (100 mL), wash aqueous layer with ethyl acetate (100 mL). Combine ethyl –50-acetate washings and dry over magnesium sulfate, filter and concentrate in vacuo. Purify (silica gel chromatography, eluting with 0: 100 to 20:80 ethyl acetate:isohexane) to give the title preparation as a white powder (560 mg, 44% yield). MS (ES): m/z = 244 [M+H]+.

The synthetic route of 41963-20-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2008/141020; (2008); A1;,
Nitrile – Wikipedia,
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