Month: August 2021

Synthetic Route of 103146-25-4, A common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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 1 50 GMS OF 4- [4- (DIMETHYLAMINO)-1- (4 -FLUOROPHENYL)-1-HYDROXYBUTYL]-3 (HYDROXYMETHYL) – benzonitrile (cyano diol) was added to a mixture of 50 gm phosphoric acid and 150 gm water. The mixture was heated to 105C for 14 hours. The reaction mixture was cooled to 40C and diluted with 1000 ml water. The pH of the solution was adjusted to 8-10 with liquor ammonia and extracted with ethyl acetate. The ethyl acetate layer was washed with 50 ML of 5% disodium edetate solution twice to remove the carboxamide impurity (about 3%) and the cyano diol impurity (about 0.8%). The ethyl acetate layer was dried over sodium sulphate, treated with decolorizing charcoal and filtered. The solution was acidified to a pH between 3-3.5 with 48% aqueous hydrobromic acid. The precipitated product of citalopram hydrobromide was filtered. This product had a purity of greater than 99.85%.

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; MEDITAB SPECIALITIES PVT. LTD; WAIN, Christopher, Paul; WO2005/12278; (2005); A2;,
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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. 17216-62-5, name is Diethyl 2-(2-cyanoethyl)malonate, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 17216-62-5

(a) Diethyl 2-(2-cyanoethyl)-2-(5-nitropyrid-2-yl)malonate Sodium hydride (53% dispersion in oil) (30.71 g, 0.66 mole) was washed by decantation with xylene (2*150 ml), ether (150 ml), tetrahydrofuran (THF) (150 ml) and finally suspended in THF (245 ml). Diethyl 2-(2-cyanoethyl) malonate (156 g, 0.73 mole) in THF (80 ml) was added dropwise over 1 hr keeping the internal temperature at 18 C. to 22 C. (with ice bath cooling). The resulting suspension cleared over 15 minutes when 2-chloro-5-nitropyridine (88.3 g, 0.55 mole) was added to give a deep magenta solution. The resulting solution was refluxed for 1 hr and the solvent was removed on the rotary evaporator. The resulting oil was partitioned between water (500 ml) and chloroform (800 ml), the pH was adjusted to ~7 (concentrated hydrochloric acid), and the chloroform was run off. The aqueous layer was extracted with a further (2*250 ml) chloroform, the extracts were combined, dried over magnesium sulphate and the solvent was removed to give an amber oil (~245 g). Ether (150 ml) was added and the solution was allowed to crystallise to give the title compound (121.98 g, 65%), m.p. 59.5-61 C. (Found C, 53.7; H. 5.05; N, 12.35%. C15 H17 N3 O6 requires C, 53.75; H, 5.1; N, 12.55%) NMR (CDCl3, 60 MHz); delta 1.37 (6 H, t); 2.65 (4 H, m); 4.26 (4 H, q); 7.84 (1 H, dd); 8.49 (1 H, dd); 9.32 (1 H, dd).

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 17216-62-5.

Reference:
Patent; Smith Kline & French Laboratories Limited; US4902698; (1990); A;,
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Application of 64248-62-0, 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 64248-62-0 as follows.

In a 500mL three-necked flask,Add 3,4-difluorobenzonitrile (50.0 g, 0.28 mol)And 200mL of absolute ethanol,Control temperature 0~5 C,Pass dry HCl gas to saturation,The reaction was kept for 30 hours, a large amount of white solid was precipitated, and suction filtration was applied. The filter cake was washed with 0 to 5 C anhydrous ethanol, and dried under vacuum to give (VI-11) 52.5 g, yield 65.9%.

According to the analysis of related databases, 64248-62-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; China Pharmaceutical University; Hefei Medical Engineering Pharmaceutical Co., Ltd.; Xu Yungen; He Guangwei; Liu Kun; Chu Zhaoxing; Zhu Qihua; Zhao Yan; Liu Weizhong; Wang Kui; Zhang Luyong; (26 pag.)CN108456152; (2018); A;,
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Related Products of 16588-02-6,Some common heterocyclic compound, 16588-02-6, name is 2-Chloro-5-nitrobenzonitrile, molecular formula is C7H3ClN2O2, 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.

Conc. HC1 (15.6 ml) was added dropwise to 2-chioro-5- nitrobenzonitrile (3.38 g, 18.5 mmol) and SnC12.2H20 (18.9 g, 83.9 mmol, 4.5 eq.) in isopropanol (35 ml). The mixture was heated at 120 C. for 2 h and then cooled to room temperature and made basic using aq. NaOH. The mixture wasextracted with dichloromethane, dried over Na2SO4 and filtered through silica gel. Concentration under reduced pressure gave 5-amino-2-chlorobenzonitrile (2.58 g, 91%).55?H NMR (300 MHz, CDC13): oe=3.90 (br. s, 2H), 6.79 (dm, 1H), 6.91 (m, 1H), 7.22-7.26 (m, 1H) ppm.

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

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; Maue, Michael; Kapferer, Tobias; Muehlthau, Friedrich August; Malsam, Olga; US9204645; (2015); B2;,
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Related Products of 52798-01-3, A common heterocyclic compound, 52798-01-3, name is Methyl (4-cyanophenyl)acetate, molecular formula is C10H9NO2, 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.

a. Methyl 2-(4-cyanophenyl)-tert.butyl malonate 1.7 g (0.01 mol) of methyl 4-cyanophenylacetate are dissolved in 30 ml tetrahydrofuran, 0.48 g (0.01 mol) of sodium hydride (60% in oil) are added in batches thereto and stirred for 15 minutes at 60 C. Then 1.5 ml (0.01 mol) of tert.butyl bromoacetate are added dropwise at ambient temperature. The reaction mixture is refluxed for 5 hours, cooled and poured onto water and extracted with methylene chloride. The combined organic extracts are dried and evaporated down. The residue is chromatographed on silica gel and eluted with petroleum ether/ethyl acetate (4:1). Yield: 1.5 g (52% of theory), Rf value: 0.7 (silica gel; petroleum ether/ethyl acetate=7:3).

The synthetic route of 52798-01-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim Pharma KG; US6114532; (2000); A;,
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Some common heterocyclic compound, 5922-60-1, name is 2-Amino-5-chlorobenzonitrile, molecular formula is C7H5ClN2, 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. SDS of cas: 5922-60-1

Example 3: Synthesis of 6-chloro-2,4-diamino-quinazolineA mixture of 2-amino-5-chlorobenzonitrile (1.07 g, 7.0 mmol), chloro- formamidine hydrochloride (1.6 g, 14 mmol), sulfolane (0.5 ml) and dimethylsulfone(3 g) was heated at 165 0C for 30 minutes. Then, water (30 ml) was added to the reaction mixture. The pH was adjusted to 7-8 by the addition of a 33 percent aqueous ammonia solution in water. The precipitate was collected by filtration, washed with water and dried over P2O5, yielding the title compound as a yellowish solid (1.35 g, yield: 99 percent) which was characterized by its mass spectrum as follows: MS (m/z): 195([M+H]+, 100).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5922-60-1, its application will become more common.

Reference:
Patent; GILEAD SCIENCES, INC.; WO2008/9077; (2008); A2;,
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These common heterocyclic compound, 63069-50-1, name is 4-Amino-3-fluorobenzonitrile, 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. SDS of cas: 63069-50-1

General procedure: 1.4.1. MethodAlj00243j A mixture of the amino aromatic or heteroaromatic starting material (1 eq), Ag2SO4 (1 eq) and 12 (1 eq) in EtOH is stirred at temperatures ranging from room temperature to 50C for a period which can vary from 1 h to approximately 16 h. The mixture is filtered, concentrated and diluted in an organic solvent. The organic mixture undergoes aqueous work up. The solvent is removed under reduced pressure and the residue is purified by flash column chromatography to yield the desired product.1.4.2. Illustrative example ofmethodAl: synthesis of 4-Amino-3-fluoro-5-iodo-benzonitrile (Int.4).N NH2 NI H2j00244j A mixture of 4-amino-3-fluorobenzonitrile (147 mmol), 12 (147 mmol) and Ag2SO4 (147 mmol) in EtOH (700 mL) was stirred at room temperature for 1.5 h. The mixture was filtered and concentrated. The residue was dissolved in EtOAc and washed (sat. Na2S2O3 x 3). The organic layer was dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (Si02, 95:5 to 70:3 0 cyclohexane/EtOAc) to yield the desired product.

The synthetic route of 4-Amino-3-fluorobenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GALAPAGOS NV; MENET, Christel, Jeanne, Marie; MAMMOLITI, Oscar; BLANC, Javier; OR?ULIC, Mislav; RO?CIC, Maja; WO2015/110378; (2015); A1;,
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Electric Literature of 51632-29-2,Some common heterocyclic compound, 51632-29-2, name is 2-(3-Phenoxyphenyl)acetonitrile, molecular formula is C14H11NO, 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 1 284 g of 3-phenoxy benzyl cyanide and 220 g of di-ethyl oxalate were mixed and 400 ml of absolute ethanol was added. To this mixture was added gradually a solution of sodium ethoxide (prepared by dissolving 31 g of sodium in 410 ml of absolute ethanol). After the addition of the ethanol solution the mixture was warmed to 50 C for 30 minutes and then allowed to stand at room temperature for 12 hours. The reaction mixture was then acidified with ice-cooled 10% sulphuric acid (prepared by adding 37 ml of concentrated sulphuric acid to sufficient ice to give 370 ml of ice-cooled diluted acid). The product was extracted with methylene dichloride and the methylene dichloride solution was then washed neutral with distilled water. The product was dried over anhydrous sodium sulphate and the solvent removed. This product was treated with cold hexane to give ethyl 3-cyano-3-(3-phenoxyphenyl)-2-ketopropionate, melting point: 105-109, 90%. The structure was confirmed with proton magnetic resonance analysis (purity > 95%). The preparation of the cyanide from the bromide is illustrated in the following example.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(3-Phenoxyphenyl)acetonitrile, its application will become more common.

Reference:
Patent; Shell Oil Company; US4010190; (1977); A;,
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Related Products of 42872-83-3,Some common heterocyclic compound, 42872-83-3, name is 2-Bromo-5-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.

MethyI-2-(pyrimidin-2-yl)benzonitrile (2); To a 500 mL three neck round bottom flask, equipped with an overhead stirrer, thermocouple and nitrogen inlet and dropped funnel, was charged 2-bromo-5-methylbenzylnitrile1 (20.00 g) and THF (60 mL, 3 V) and was cooled to -15 C. 1.3 M of i-PrMgCI’LiCl (1 10.0 mL, 1.4 equiv) was slowly added at -15 to -12 C. The reaction mixture was stirred at -15 to -12 C for 3.5 h (> 99 A% conversion). 15.45 g of anhydrous ZnCl2 (1.1 equiv, powder) was added to the Grignard reagent at -12 C in one portion. The reaction was exothermic raising the temperature of the reaction mixture to 0 C. The reaction mixture was stirred at -3 to 2 C for 0.5 h and slowly warmed to rt over 0.5 h. The reaction mixture became a homogenous solution and then 2-chloropyrimidine (15.37 g) was added.To a slurry of 1 mol% Pd(OAc)2 (0.229 g), 4 mol% («-Bu)3P (0.826 g or 1.02 mL) in THF (8 mL) was added 2.0 M of BuMgCl (1.02 mL) THF solution to become yellow cloudy solution, The resulting catalyst solution was added to the reaction mixture. The resulting mixture was heated at 55 C for 17 h: (98 A% conversion). The reaction mixture was solvent-switched to isopropyl alcohol (140 mL, total volume) at 40-45 C. Then 5 wt% NH4C1 aqueous solution (70 mL) was added dropwise at 15 to 20 C. The resulting slurry was aged at 10 C for 5 h. The crystalline solid was collected by filtration, rinsed with cold isopropyl alcohol/water (1 : 1, 35 mL), and ^-heptane (30 mL), dried under vacuum with nitrogen sweep and gave desired product2 (17.33 g, 87% isolated yield, 99.5 LCAP purity).HPLC MethodColumn: Zorbax Eclipse Plus CI 8 50 x 4.6 mm, 1.8 muetaiota particle size, Column Temp.: 25 C; Flow Rate: 1.5 mL/min; Detection: 230 nm; Mobile Phase: A: Water 0.1% H3PO4, B: AcetonitrileMobile Phase Program: Time A0 90%5 min 5%6 min 5%6.1 min 90%8 min 90%Compound 2: 3.19 min

The synthetic route of 42872-83-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; FENG, Yun Shao; MOSES, Anthony; ZHONG, Yong-Li; WO2012/58129; (2012); A1;,
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Application of 59997-51-2,Some common heterocyclic compound, 59997-51-2, name is 4,4-Dimethyl-3-oxopentanenitrile, molecular formula is C7H11NO, 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.

4,4-Dimethyl-3-oxopentanenitrile (80 mmol, 10 g)At room temperature EtOH (200 mL)And stirred at 0 C, hydrazine monohydrate(160 mmol, 7.74 ml) was slowly added. Heated to 90 C and refluxed for 3 hours. After the reaction was completed, the reaction mixture was cooled at room temperature, and the solvent was removed under reduced pressure. Diluted with water, extracted with EtOAc Respectively. Sodium sulfate was added to the extracted organic solvent to remove residual water, and the resultant was separated by MPLC to obtain a red solid Was prepared in a yield of 57%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4,4-Dimethyl-3-oxopentanenitrile, its application will become more common.

Reference:
Patent; Korea Research Institute of Chemical Technology; Lee, Kwang Ho; Choe, Gil Don; Park, Sang Jun; Lee, Na Li; Jung, Myung Eun; Kim, Sung Jin; Yang, Kyung Min; Lee, Ji Hee; (28 pag.)KR101726648; (2017); B1;,
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