Author: Jessica.F

Related Products of 157662-77-6, These common heterocyclic compound, 157662-77-6, name is 4-Fluoro-3-nitrophenylacetonitrile, 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 mixture of 2-(4-fluoro-3-nitrophenyl)acetonitrile (5.8 g, 32.2 mmol) and diisobutyl amine (20.8 g, 161 mmol) was stirred at 130C under N2 atmosphere for 2 hr. The resulting mixture was partitioned between EtOAc and H20. The layers were separated and the organic layer was washed with brine, dried over Na2S04, filtered and concentrated to give the crude product which was purified by flash chromatography (silica gel, 0-20% EtOAc in PE) to afford the title compound (8.0 g, 86% yield). LCMS (ESI) m/z calcd for Ci6H23N302: 289.18. Found: 290.76 (M+1 )+.

The synthetic route of 157662-77-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; DE LA ROSA, Martha Alicia; KAZMIERSKI, Wieslaw Mieczyslaw; SAMANO, Vicente; (369 pag.)WO2018/116107; (2018); A1;,
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Synthetic Route of 877131-92-5, 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 877131-92-5 as follows.

Add hydrochloric acid (2 mL, 12M) to a solution of 2-[ 4-bromo-2(trifluoromethyl)phenyl]acetonitrile (600 mg, 2.25 mmol) in acetic acid (2 mL), the mixture is stirred at 100 C for 2 h under nitrogen. The reaction mixture is concentrated to afford title 5 compound (600 mg, 89.5%) as colorless oil. 1H NMR (400MHz, CD3Cl) () = 7.82 (d, J = 1.6 Hz, 1H), 7.67 (dd, J = 1.6, 8.4 Hz, 1H), 7.29 (s, 1H), 3.83 (s, 2H).

According to the analysis of related databases, 877131-92-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ELI LILLY AND COMPANY; LILLY CHINA RESEARCH AND DEVELOPMENT CO., LTD.; MA, Tianwei; WU, Liang; ZHANG, Xuejun; (109 pag.)WO2019/41340; (2019); A1;,
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Reference of 80517-21-1,Some common heterocyclic compound, 80517-21-1, name is 4-Fluoro-2-nitrobenzonitrile, molecular formula is C7H3FN2O2, 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 106(1)2-Amino-4-{4-chloro-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzamide (106a)Compound (6b) (0.335 g) was dissolved in DMF (8.6 mL), and sodium hydride (0.097 g, a 55% dispersion in paraffin liquid) was added to the resulting solution at 0 C., followed by stirring for 30 min. Then, 4-fluoro-2-nitrobenzonitrile was added to the reaction solution, followed by stirring at 60 C. for 30 min. Water was added to the reaction solution, and the precipitate was collected by filtration and washed by sprinkling water to obtain 4-{4-chloro-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}-2-nitrobenzonitrile (0.5 g, 85%). 4-{4-Chloro-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}-2-nitrobenzonitrile (0.35 g) and ammonium chloride (0.35 g) were dissolved in a solvent mixture of THF (3 mL), methanol (3 mL), and water (3 mL). Iron (0.57 g) was added to the resulting solution, followed by stirring at 70 C. for 1 hr. Insoluble matters were filtered by celite, and the solvent was distilled away. The precipitate was washed with water and was collected by filtration to obtain compound (106a) (0.32 g, 95%) as a white solid.1H-NMR (DMSO-d6) delta: 8.57 (1H, d, J=4.88 Hz), 7.70 (1H, d, J=9.27 Hz), 7.60 (1H, d, J=1.95 Hz), 7.47 (1H, d, J=4.88 Hz), 7.45 (1H, dd, J=9.27, 1.95 Hz), 6.92 (2H, brs), 3.73 (1H, tt, J=6.83, 6.83 Hz), 1.43 (6H, d, J=6.83 Hz); LRMS (ESI) m/z 330 [M+H]+.

The synthetic route of 80517-21-1 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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Electric Literature of 395675-23-7,Some common heterocyclic compound, 395675-23-7, name is 2-Chloro-5-fluorophenylacetonitrile, molecular formula is C8H5ClFN, 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.

[0591] To a solution of (2-chloro-5-fluorophenyl)acetonitrile (10.0 g, 59.0 mmol) in THF (75 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (44 ml, 88 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, tert-butyl 3-bromopropanoate (11 ml, 71 mmol) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water was added gradually to the mixture, which was extracted twice with ethyl acetate. The combined organic phases were washed once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated, and the residue was purified by flash column chromatography (340 g silica gel Biotage Snap-Cartridge KP-Sil, cyclohexane/ethyl acetate gradient 93:7?3:7, Isolera One). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 14.8 g (93% purity, 78% of theory) of the title compound. [0592] LC-MS (Method 1): Rt=2.22 min; MS (ESIpos): m/z=298 [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-Chloro-5-fluorophenylacetonitrile, its application will become more common.

Reference:
Patent; Bayer Aktiengesellschaft; Bayer Pharma Aktiengeseiisehaft; BECK, Hartmut; KAST, Raimund; MEININGHAUS, Mark; DIETZ, Lisa; FUERSTNER, Chantal; STELLFELD, Timo; ANLAUF, Sonja; VON BUEHLER, Clemens-Jeremias; BAIRLEIN, Michaela; ANLAHR, Johanna; MUENSTER, Uwe; TERJUNG, Carsten; JOERISSEN, Hannah; HAUFF, Peter; MUELLER, Joerg; DROEBNER, Karoline; NAGEL, Jens; (220 pag.)US2020/31775; (2020); A1;,
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Electric Literature of 447-60-9, These common heterocyclic compound, 447-60-9, name is 2-(Trifluoromethyl)benzonitrile, 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: The mixture of 1-ferrocenyl-2-methylpropan-1-ol (1) (645 mg, 2.5 mmol) and the nitrile 2 (2.5 or 3.0 mmol) in DCE(5 mL) was added dropwise with vigorous stirring to MsOH (1.30 mL, 20 mmol) at room temperature. The resulting mixture was then heated with stirring at 60 C for the noted reaction time. After, the reaction mixture was cooled to roomtemperature, poured into a mixture of crushed ice (20 g) and 25% aq NH3 (6 mL) and extracted with EtOAc (80 mL × 3). The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification of the crude mixture by silica gel column chromatography gave the desired product 3

Statistics shows that 2-(Trifluoromethyl)benzonitrile is playing an increasingly important role. we look forward to future research findings about 447-60-9.

Reference:
Article; Rozhkova, Yuliya S.; Plekhanova, Irina V.; Gorbunov, Alexey A.; Stryapunina, Olga G.; Chulakov, Evgeny N.; Krasnov, Victor P.; Ezhikova, Marina A.; Kodess, Mikhail I.; Slepukhin, Pavel A.; Shklyaev, Yurii V.; Tetrahedron Letters; vol. 60; 11; (2019); p. 768 – 772;,
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Synthetic Route of 13519-90-9, These common heterocyclic compound, 13519-90-9, name is 4-Fluoroisophthalonitrile, 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-hydroxytetrahydropyran (14 g, 140 mmol) was taken up in tetrahydrofuran (300 mL) and cooled in an ice-water bath. Potassium tert-butoxide (17 g, 150 mmol) was added, and the reaction mixture was stirred for 20 minutes in the bath before the addition of 4-fluoroisophthalonitrile (10 g, 68 mmol). The mixture continued to stir in the bath for 5 minutes before the removal of the bath. The mixture was stirred at room temperature overnight and then concentrated almost to dryness under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined organics were washed once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, concentrated to dryness under reduced pressure. The residue was recrystallized from methanol to provide 4-((tetrahydro-2H-pyran-4-yl)oxy)isophthalonitrile. 1H NMR (400 MHz, DMSO-d6) delta 8.42 (d, J=2.1 Hz, 1H), 8.16 (dd, J=8.9, 2.1 Hz, 1H), 7.60 (d, J=9.0 Hz, 1H), 5.01 (m, 1H), 3.88 (m, 2H), 3.57 (m, 2H), 2.05 (m, 2H), 1.70 (m, 2H).

The synthetic route of 13519-90-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gilead Sciences, Inc.; Du, Zhimin; Guerrero, Juan A.; Kaplan, Joshua A.; Knox, JR., John E.; Lo, Jennifer R.; Mitchell, Scott A.; Naduthambi, Devan; Phillips, Barton W.; Venkataramani, Chandrasekar; Wang, Peiyuan; Watkins, William J.; Zhao, Zhongdong; (593 pag.)US2016/96827; (2016); A1;,
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Adding a certain compound to certain chemical reactions, such as: 143879-78-1, name is 3-Amino-2,6-difluorobenzonitrile, 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 143879-78-1, Computed Properties of C7H4F2N2

Example 4: 2,6-Difluoro-3-[5-(3-morpholin-4-ylphenoxy)-pyrimidin-2-ylamino]- benzonitrileA suspension of 4-[3-(2-chloro-pyrimidin-5-yloxy)phenyl]morpholine (180mg, 0.619 mmol), 3-amino-2,6-difluorobenzonitrile (95.3mg, 0.619mmol), ira(dibenzylidene- acetone)palladium(O) (28.3mg, 0.030mmol), 4,5-bis,(diphenylphosphino)-9,9- dimethyl-xanthene (35.8mg, 0.061mmol) and cesium carbonate (403mg, 1.238mmol) in degassed 1,4-dioxane (4mL) was heated at 80C for 2 days. The suspension was diluted with ethyl acetate and washed with water and brine. The organic phase was dried (MgS04) and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica (ethyl acetate:hexane, 1: 1) to afford 2,6-difluoro-3-[5-(3-morpholin-4-ylphenoxy)pyrimidin-2-ylamino]benzonitrile as a solid (l lOmg, 44%).Mass: (ES+) 410 (M+H)+ HPLC: 99.2%NMR: deltaEta ( 6-DMSO) 3.08 (4H, m), 3.69 (4H, m), 6.34 (IH, dd), 6.60 (IH, br s), 6.69 (IH, dd), 7.18 (IH, t), 7.40 (IH, t), 8.10 (IH, m), 8.35 (2H, s) and 9.59 (IH, s).

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, 3-Amino-2,6-difluorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SENEXIS LIMITED; HORWELL, David; SCOPES, David; WO2011/144577; (2011); A1;,
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Synthetic Route of 36764-94-0, 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 36764-94-0 as follows.

General procedure: A solution of 2,4,6-trisubstitutedphenylamine (10, 0.8 mmol) in pyridine (10 mL) was added to the flask containingt he crude acyl chloride 8 (0.8 mmol) which was prepared from the procedure described above, and the mixture was refluxed for 3-5 h. After cooling down, the mixture was poured into water (50 mL) and extracted with ethyl acetate (3× 15 mL). The extracts were combined and washed with hydrochloric acid (2 × 10 mL) and brine, successively. The organic phase was dried over anhydrous Na2SO4. After solvent removal, the residue was further purified by recrystallization from ethanol to afford the title compound 12(a-c) as a solid.

According to the analysis of related databases, 36764-94-0, the application of this compound in the production field has become more and more popular.

Reference:
Article; Wang, Baolei; Wang, Hongxue; Liu, Hang; Xiong, Lixia; Yang, Na; Zhang, Yan; Li, Zhengming; Chinese Chemical Letters; vol. 31; 3; (2020); p. 739 – 745;,
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Related Products of 13726-21-1, These common heterocyclic compound, 13726-21-1, name is 2-(4-Chloro-3-methoxyphenyl)acetonitrile, 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.

BBr3 (17 g, 66 mmol) was slowly added to a solution of 2-(4-chloro-3-methoxyphenyl)acetonitrile (12 g, 66 mmol) in dichloromethane (120 mL) at -78 C. under N2. The reaction temperature was slowly increased to room temperature. The reaction mixture was stirred overnight and then poured into ice and water. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (40 mL*3). The combined organic layers were washed with water, brine, dried over Na2SO4, and concentrated under vacuum to give (4-chloro-3-hydroxy-phenyl)-acetonitrile (9.3 g, 85%). 1H NMR (300 MHz, CDCl3) delta 7.34 (d, J=8.4 Hz, 1H), 7.02 (d, J=2.1 Hz, 1H), 6.87 (dd, J=2.1, 8.4 Hz, 1H), 5.15 (brs, 1H), 3.72 (s, 2H).

Statistics shows that 2-(4-Chloro-3-methoxyphenyl)acetonitrile is playing an increasingly important role. we look forward to future research findings about 13726-21-1.

Reference:
Patent; Vertex Pharmaceuticals Incorporated; Van Goor, Fredrick F.; Burton, William Lawrence; US2015/231142; (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. 27387-23-1, name is 2-(2-Bromo-5-methoxyphenyl)acetonitrile, A new synthetic method of this compound is introduced below., Product Details of 27387-23-1

D. N, N-DIMETHYL-5-METHOXY-2-BROMOPHENYLACETAMIDE 5-Methoxy-2-bromobenzoic acid (85 g, 0.37 mol) is dissolved in anhydrous THF (100 mL) and cooled in an ice-salt bath until the temperature REACHES-5 C. Borane-THF complex is added dropwise as a 1.0 M solution in THF (736 mL, 0.74 mol) AT-5C. After addition is complete, the reaction mixture is slowly warmed to room temperature and stirred for 12 hours. Water (40 mL) is slowly added dropwise and the reaction mixture stirred for 30 minutes. Additional water (350 mL) is added and the mixture is concentrated by rotary evaporator to remove most of the THF. The remaining material is extracted with EtOAc (800 mL). The organic layer is washed with saturated NAHCO3 (500 mL), brine (250 mL) and then dried (NA2SO4). UPON REMOVAL of the solvent by rotary evaporator, 5-methoxy-2- bromobenzyl alcohol is obtained as a white solid. 5-Methoxy-2-bromobenzyl alcohol (79.5 g, 0.37 mol) is dissolved in 48% HBr (400 mL) and heated to reflux temperature for 4 hours. The reaction mixture is cooled to room temperature and poured into water (1500 mL). The solution is extracted with EtOAc (2 x 500 mL). The combined organic layers are dried (MGS04) and concentrated by rotary evaporator. The crude material is then purified using flash chromatography (CH2CI2/hexanes, from 1: 1 to 4: 1) to give 5-methoxy-2-bromobenzyl bromide. 5-METHOXY-2-BROMOBENZYL bromide (72.8 g, 0.26 mol) is dissolved in EtOH (280 mL) and stirred at room temperature. Sodium cyanide (38.2 g, 0.78 mol) is dissolved in water and added to the solution of the bromide. The reaction mixture is heated to reflux temperature for 3 hours and then cooled to room temperature. Most of the ethanol is removed by rotary evaporator. A solid forms which is isolated by filtration and washed with water (500 mL). The crude material is purified using flash chromatography (CH2CI2/HEXANES, 1: 1) to give 5-methoxy-2-bromophenylacetonitrile (53 g). 5-Methoxy-2-bromophenylacetonitrile (52.8 g, 0.23 mol) is dissolved in ethanol (250 mL) and stirred at room temperature. Sodium hydroxide (9.3 g, 0.47 mol) is dissolved in water (150 mL) and added to the solution of the nitrile. The mixture is heated to reflux temperature for 12 hours and then cooled to room temperature. Most of the ethanol is removed using a rotary evaporator and the residual aqueous solution adjusted to pH 4 with 3 N HCI. The solid which forms is isolated by filtration and washed with water. Air drying gives 5-methoxy-2-bromophenylacetic acid. 5-Methoxy-2-bromophenylacetic acid (56 g, 0.23 mol) is dissolved in CH2CI2 (350 mL) and a catalytic amount of DMF is added and the solution stirred and cooled to 0C. Thionyl chloride (41 mL, 0.34 mol) is added dropwise. The reaction mixture is heated at reflux temperature overnight and then cooled to room temperature. Solvents are removed by rotary evaporator. Twice benzene (500 mL) is added to the residual oil and the benzene solution is evaporated by rotary evaporator to remove any additional volatile components. The residual oil is crystallized from hexanes to give 5-methoxy-2-bromophenylacetyl chloride. 5-Methoxy-2-bromophenylacetyl chloride (60 g, 0.23 mol) is dissolved in anhydrous ET20 (400 mL), stirred and cooled in an ice bath. A 2 M solution of DIMETHYLAMINE (228 mL, 0.46 mol) is added dropwise and the mixture allowed to warm to room temperature and stirred for 2 hours. Additional ET20 (500 mL) is added. The organic solution is washed with 1 N HCI (2 x 500 mL), saturated NAHCO3 (500 mL) and brine (500 mL). The organic layer is dried (NA2SO4) and concentrated by rotary evaporator. The residue is purified using flash chromatography (hexanes/EtOAc, from 7: 3 to 1: 9). Trituration of the crude product with ET20/HEXANES gives N, N-DIMETHYL-5-METHOXY-2-BROMOPHENYLACETAMIDE AS a white crystalline solid (m. p. 88-90C).

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; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2004/48314; (2004); A1;,
Nitrile – Wikipedia,
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