Category: nitriles-buliding-blocks

Electric Literature of 1897-52-5, A common heterocyclic compound, 1897-52-5, name is 2,6-Difluorobenzonitrile, molecular formula is C7H3F2N, 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 156A 2-Fluoro-6-(1H-1,2,4-triazol-1-yl)benzonitrile Under argon, 2,6-difluorobenzonitrile (1.00 g, 7.19 mmol) was dissolved in dimethylsulfoxide (4 mL), and 1,2,4-triazole (0.52 g, 7.48 mmol) and cesium carbonate (2.44 g, 7.48 mmol) were added. The mixture was stirred at 50 C. for 5 h. After cooling to RT, water (20 mL) was added and stirring was continued for 15 min. The precipitate was filtered and washed with water (10 mL). The solid was taken up in dichloromethane/water and extracted with dichloromethane. The combined organic phases were washed with brine, and concentrated in vacuo. Purification via column chromatography (silica gel, cyclohexane/ethyl acetate, Gradient) afforded the title compound (0.25 g, 18% of theory). LC-MS (Method 1B): Rt=0.62 min, MS (ESIPos): m/z=189 [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; BAYER PHARMA AKTIENGESELLSCHAFT; Hassfeld, Jorma; KINZEL, Tom; Koebberling, Johannes; CANCHO GRANDE, Yolanda; BEYER, Kristin; Roehrig, Susanne; Koellnberger, Maria; SPERZEL, Michael; BURKHARDT, Nils; SCHLEMMER, Karl-Heinz; STEGMANN, Christian; SCHUHMACHER, Joachim; WERNER, Matthias; ELLERMANN, Manuel; US2015/126449; (2015); 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. 326-62-5, name is 2-(2-Fluorophenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C8H6FN

Example 1a Preparation of 2-(2-fluorophenyl)-2-methylpropanenitrile To a 500 mL 3-neck round bottom flask with an attached addition funnel that has been purged with dry N2, was added 2-fluorophenylacetonitrile (11.0 g, 81.4 mmol) and anhydrous THF (70 mL). The reaction solution was cooled to -10 C. prior to dropwise addition of a 1.0 M potassium tert-butoxide solution (195 mL, 2.4 molar equiv) in THF. The reaction solution was stirred at -10 C. for 20 min prior to addition of iodomethane (15.2 mL, 244 mmol). The reaction solution was allowed to stir warming to room temperature for 4 hr. The reaction solution was quenched by addition of aq NH4Cl and diluted with EtOAc (200 mL). The organic phase was partitioned, washed with aq NH4Cl, dried over Na2SO4, filtered, concentrated in vacuo and chromatographed through a 240 g SiO2 column on the Biotage SP-1 using a solvent gradient of 100% Hx to 50% EtOAc to afford 10.1 g (76% yield) of title product. GCMS m/z=163 [M]+.

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 326-62-5.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; EXELIXIS PATENT COMPANY LLC; Busch, Brett B.; Stevens, JR., William C.; Kick, Ellen K.; Zhang, Haiying; Bollu, Venkataiah; Martin, Richard; Mohan, Raju; US2015/299136; (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. 57381-49-4, name is 2-Bromo-4-chlorobenzonitrile, A new synthetic method of this compound is introduced below., name: 2-Bromo-4-chlorobenzonitrile

[0911] To a solution of 100 g (654 mmol) of (2-methoxy- pyridin-4-yl)boronic acid and 142 g (654 mmol, 1 eq.) of 2-bromo-4-chlorobenzonitrile in 2.01 of dioxane were added981 ml (1961 mmol, 3 eq.) of 2 N aqueous sodium carbonate solution. Argon was passed through the reaction mixture for 10mm, 53mg (65 mmol, 0.1 eq.) of[1,1-bis(diphenylphos- phino)ferrocene] dichloropalladium dichioromethane complex were added and the mixture was stirred at 85 C. for 6 h. The mixture was then stirred at RT overnight. The reaction mixture was admixed with 3 1 of water and 1 1 of methyl tert-butyl ether, filtered through kieselguhr and washed through with 11 of methyl tert-butyl ether. The filtrate was separated and the aqueous phase was extracted twice with 1 1 of methyl tert-butyl ethet The combined organic phases were dried over sodium sulphate and concentrated. The filtercake was washed three times with 800 ml of dichloromethane and the organic phase was dried over sodium sulphate and concentrated. Subsequently, the two residues were combined and stirred in methanol. The precipitate was filtered oil with suction and washed twice with methanol. The filtrate was concentrated and dissolved together with the precipitate in dichloromethane. Subsequently, activated carbon was added and the mixture was stirred under reflux for 30 mm. The reaction mixture was subjected to hot filtration through kieselguhr, and the filtrate was concentrated. The residue was stirred again in methanol, and the precipitate was filtered off with suction and washed twice with methanol. The filtrate was concentrated, and the precipitate was filtered off with suction and washed with methanol. The two precipitates were combined and dried under high vacuum overnight. The filtrate was concentrated and purified by means of flash chromatography (eluent: dichloromethane/ methanol, 0-2%). The product fractions were combined, concentrated and stirred in warm methanol. The precipitate was filtered off with suction, washed with methanol and dried under high vacuum. Overall yield: 120 g (75% of theory).10912] LC/MS [Method 1]: R=1.02 mm; MS (ESIpos):mlz=245 (M+H), j0913] ?H-NMR (400 MHz, DMSO-d5): oe [ppm]=8.33 (d, 1H), 8.04 (d, 1H), 7.82 (d, 1H), 7.76 (dd, 1H), 7.22 (dd, 1H),7.07 (s, 1H), 3.92 (s, 3H).

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; BAYER PHARMA AKTIENGESELLSCHAFT; ROeHRIG, Susanne; JIMENEZ-NUNEZ, Eloisa; SCHLEMMER, Karl-Heinz; TERSTEEGEN, Adrian; TELLER, Henrik; HILLISCH, Alexander; HEITMEIER, Stefan; SCHMIDT, Martina Victoria; ACKERSTAFF, Jens; STAMPFUss, Jan; (87 pag.)US2017/291892; (2017); A1;,
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42872-74-2, name is 3-Bromo-4-methylbenzonitrile, 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. name: 3-Bromo-4-methylbenzonitrile

[0097] The solution of 3-bromo-4-methylbenzonitrile (3) (2.0 g, 10 mmol), in DMF (12 mL) with Bis(pinacolato)diboron (3.4 g, 13 mmol), and Pd(OAc)2 (0.5 g, 2 mmol), and KOAc (3 g, 30 mmol) was microwaved for 3 h at 80C. The mixture was then diluted with H2O (25 mL) and extracted with EtOAc (2 x 30 mL). [0098] The organic phase was collected and dried over Na2SO4 Column chromatography (in Hexane/Ethyl acetate 9:1) afforded 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (B) as an oil, which solidified during the drying in vacuo (yield: 96%)

The synthetic route of 42872-74-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SYNTA PHARMACEUTICALS CORP.; CHEN, Shoujun; ZHANG, Junyi; JIANG, Jun; KOWALCZYK-PRZEWLOKA, Teresa; XIA, Zhiqiang; ZHANG, Shijie; WO2013/63385; (2013); A1;,
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Synthetic Route of 38487-86-4,Some common heterocyclic compound, 38487-86-4, name is 2-Amino-4-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.

2-Amino-4-chlorobenzonitrile(153 mg, 1 mmol), [Cp * IrCl2] 2 (8 mg, 0.01 mmol, 1 mol%),Butyraldehyde oxime (96 mg, 1.1 mmol), p-xylene (2.0 mL) were sequentially added to a 25 mL Schlenk reaction flask.After the mixture was reacted at 70 C for 12 hours, cooled to room temperature, and then added to a 25 mL Schlenk flaskBenzaldehyde (117 mg, 1.1 mmol) was added. The mixture was further reacted at 110 C for 4 hours and then cooled toThe solvent was removed under vacuum at room temperature. Then through several petroleum ether washing, filtration, drying to be pure goalCompound, yield: 91%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-4-chlorobenzonitrile, its application will become more common.

Reference:
Patent; Nanjing University of Science and Technology; Zhao Wei; Wang Rongzhou; Li Feng; (17 pag.)CN106478525; (2017); A;,
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Synthetic Route of 50397-74-5, The chemical industry reduces the impact on the environment during synthesis 50397-74-5, name is 4-Amino-3-bromobenzonitrile, I believe this compound will play a more active role in future production and life.

Diethyl ethoxymethylenemalonate (8.23 g, 38.1 mmol) was added to a solution of 1 (5.00 g, 25.4 mmol) in 30 mL of toluene. The mixture was then heated to reflux overnight with the condenser open to the air. The resulting solution was cooled down to room temperature and poured into 100 mL of hexanes. The white precipitate was collected and washed with hexanes (3 * 30 mL) to yield 11.9 g of an off-white solid as the desired product. MS ESI (m/z) 367 (M + 1)+; 1H NMR (CDCl3, 300 MHz): delta 11.44 (d, 1H, J = 12.6 Hz), 8.44 (d, 1H, J = 12.9 Hz), 7.86 (d, 1H, J = 1.8 Hz), 7.63 (dd, 1H, J1 = 1.8 Hz, J2 = 8.7 Hz), 7.33 (d, 1H, J = 8.4 Hz), 4.35 (q, 2H, J = 6.9 Hz), 4.27 (q, 2H, J = 6.9 Hz), 1.38 (t, 3H, J = 6.9 Hz), 1.33 (t, 3H, J = 6.9 Hz).

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-Amino-3-bromobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Fiorito, Jole; Saeed, Faisal; Zhang, Hong; Staniszewski, Agnieszka; Feng, Yan; Francis, Yitshak I.; Rao, Sudha; Thakkar, Devarshi M.; Deng, Shi-Xian; Landry, Donald W.; Arancio, Ottavio; European Journal of Medicinal Chemistry; vol. 60; (2013); p. 285 – 294;,
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Electric Literature of 115661-37-5, A common heterocyclic compound, 115661-37-5, name is 2-Amino-3-fluorobenzonitrile, molecular formula is C7H5FN2, 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.

To 100 mL of the round bottom flask was added 1 g (about 7.35 mmol) of 2-amino-3-fluorobenzonitrile, 4.88 mL (about 36.73 mmol) of N,N-dimethylformamide dimethyl acetal and 15 mL of solvent methanol. The reaction in the round bottom flask was then stirred under reflux for 6 hours. The solvent and excess reactants are removed by distillation under reduced pressure. Intermediate (E)-N’-(2-cyano-6-fluorophenyl)-N,N-dimethylformamidine 1.4 g is obtained. The yield is 99%,

The synthetic route of 115661-37-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhengzhou University; Liu Hongmin; Yu Bin; Yuan Shuo; Zhang Danqing; (31 pag.)CN110078675; (2019); A;,
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Reference of 98730-77-9,Some common heterocyclic compound, 98730-77-9, name is 1-(Hydroxymethyl)cyclopropanecarbonitrile, molecular formula is C5H7NO, 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 stirred mixture of 1-(hydroxymethyl)cyclopropanecarbonitrile (24.30mmoi, 2.36g) in dichioromethane (3OmL) was treated with triethylamine (48.deltammol, 6.83mL, 4.92g) and portiortwise with methanesuifonyl chloride (31.deltammol, 2.445mL, 3.62g) keeping the reaction mixture at O0C. The solution was allowed to stir for 1 hour then diluted with saturated sodium hydrogencarbonate and extracted with 10% methanol/dichloromethane (x3). The organic layers were combined and concentrated under reduced pressure to give the intermediate (i-cyanocydopropyl)methyl methanesutfonate (3.77g).1H NMR (CDCI3, 400 MHz): delta 1.18 (2H, m), 1.46 (2H, m), 3,14 (3H, s), 4.18 (2H, s)

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

Reference:
Patent; N.V. ORGANON; PHARMACOPEIA, LLC; COOKE, Andrew, John; BENNETT, David, Jonathan; EDWARDS, Andrew Stanley; ROUGHTON, Andrew Laird; NEAGU, Irina; CHAN, Jui-Hsiang; HO, Koc-Kan; ANSARI, Nasrin; MORRIS, Michelle Lee; RONG, Yajing; OHLMEYER, Michael; WO2010/25179; (2010); A1;,
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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 69395-13-7 as follows. Safety of 4-(2-Hydroxyethyl)benzonitrile

To a stirred solution of 4-(2-hydroxyethyl)benzonitrile (1.0g ,6.8mmol,1eq.) in DCM (20 mL) was added CBr4 (4.5016g, 13.6mmol, 2.0 eq) and TPP (3.835g, 13.6mmol, 2.0 eq). The resulting solution was stirred at RT for 5h. Reaction was monitored TLC. Reaction was diluted with water and extracted with EtOAc. Organic layer was dried over sodium sulfate, filtered and the filtrated concentrated. The crude compound was isolated by column chromatography to get pure 4-(2-bromoethyl)benzonitrile (1.3 g, 91%). LC-MS (method 23): Rt = 2.01 min; m/z = 210.05 (M+H+).

According to the analysis of related databases, 69395-13-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ORYZON GENOMICS, S.A.; SALAS SOLANA, Jorge; CARCELLER GONZALEZ, Elena; ORTEGA MUNOZ, Alberto; (195 pag.)WO2018/149986; (2018); A1;,
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Application of 22364-68-7, A common heterocyclic compound, 22364-68-7, name is 2-(o-Tolyl)acetonitrile, molecular formula is C9H9N, 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.

Part A: Preparation of ethyl 2-(alpha-cyano-2′-methylphenylacetyl)cyclohexyl carboxylate Using the procedure described in Example I, Part A, and starting with 159.80 g (0.700 mol) of diethyl 1,2-cyclohexanedicarboxylate, 61.65 g (0.47 mol) of 2-methylbenzyl cyanide, 14.06 g (0.61 mol) of sodium, and 250 ml of ethanol, 87.74 g (60% yield) of the desired cyano keto ester was obtained as a red, viscous oil.

The synthetic route of 22364-68-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Union Carbide Corporation; US4283348; (1981); A;,
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