Month: September 2021

Adding a certain compound to certain chemical reactions, such as: 3939-09-1, name is 2,4-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 3939-09-1, name: 2,4-Difluorobenzonitrile

Example 8a Preparation of 4-Fluoro-2-(tetrahydro-pyran-4-ylamino)-benzonitrile A mixture of 2,4-difluorobenzonitrile (0.420 g, 3.0 mmol), 4-aminotetrahydropyran (0.306 g, 3.0 mmol) and DIPEA (0.523 mL, 3.0 mmol) in DMSO (5.0 mL) is stirred at 150 C. (preheated oil-bath) for 20 min. After cooling to room temperature, the resulting mixture is poured into saturated aqueous NH4Cl solution and extracted with ethyl acetate (3*20 mL). The combined organic layer is washed with brine (3*15 mL) and dried over Na2SO4, filtered and concentrated at reduced pressure to dryness. The residue obtained is purified by column chromatography (silica gel, 40:60 ethyl acetate/hexane) to afford 4-Fluoro-2-(tetrahydro-pyran-4-ylamino)-benzonitrile (0.214 g, 32%) as a pale yellow solid: ESI MS m/z 221 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,4-Difluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; SERENEX, INC.; US2008/119457; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 766-84-7,Some common heterocyclic compound, 766-84-7, name is 3-Chlorobenzonitrile, molecular formula is C7H4ClN, 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 a 400 L glass lined vessel was charged 1,3-dibromo-5,5-dimethyl-hydantoin (DBH) (10.88 kg, 38.6 mol), followed by methane sulfonic acid (111.4 kg). The resulting slurry was warmed to 35 C. to form a DBH solution. [0306] To a separate 400 L vessel was charged 3-chlorobenzonitrile 1-1 (8.050 kg, 58.5 mol, Acros, Lancaster) melt and cyclohexane (1.8 L total), followed by methanesulfonic acid (47.6 kg) to form a benzonitrile solution, which was warmed to 25-30 C. to dissolve any solids. The DBH solution was added to the benzonitrile solution over a period of about 30 minutes with fast agitation while maintaining a batch temperature of <30 C. The empty DBH solution containing vessel was rinsed with methane sulfonic acid (5.0 kg) and the rinse was added to the reaction mixture. The reaction was aged at 30 C. for 1 to 2 hours to affect reaction conversion >95 area % (tracked via HPLC assay). The reaction was then cooled to about 14 C. and slowly quenched with water (80.5 L) to maintain a temperature of <30 C. The reaction was then re-cooled to 20 C. and MTBE was added (208.5 kg) at <30 C. under agitation. The mixture was allowed to settle, the layers were separated and the aqueous layer was extracted with 101 kg of MTBE at 30 C., followed by 30 kg of MTBE. The organic layers were combined and washed with 50 kg 1.6 N NaOH, and 54 kg water, and then concentrated to 48 L, cooled and seeded (10 g of seed). Once a slurry formed, the concentration was resumed until a batch volume of 40 L was achieved. The resulting slurry was aged at 20 C. for 1.5 hours and then filtered. The cake was washed with 12 kg of 1:1 MTBE:cyclohexane (in 2 drops). The wet solids were dried in a filter dryer to give 1-2. 1H NMR (CDCl3, 400 MHz) delta 7.39 (d, J=2.2 Hz, 1H), 7.22 (dd, J=2.3, 8.4 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H) The synthetic route of 766-84-7 has been constantly updated, and we look forward to future research findings. Reference:
Patent; Boice, Genevieve N.; Conrad, Karen M.; Corley, Edward G.; Matty JR., Louis; Murry, Jerry A.; Savarin, Cecile G.; US2004/181070; (2004); A1;,
Nitrile – Wikipedia,
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Application of 6136-93-2, These common heterocyclic compound, 6136-93-2, name is 2,2-Diethoxyacetonitrile, 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.

Diethoxyacetamidine hydrochloride was synthesized according to the literature method.3 To a solution of sodium methoxide (0.09 g, 1.6 mmol) in methanol (8.4 mL) was added diethoxyacetonitrile (2.00 g, 15.5 mmol) and the reaction mixture was stirred for 4 hours at room temperature. Solid carbon dioxide (0.5 g) was added and most of the methanol was evaporated. Diethyl ether was added and the sodium carbonate was removed by filtration.The filtrate was concentrated to afford methyl diethoxyacetimidate as a colorless oil (2.47 g, 99 % yield) which was used in the next step without further purification. The oil was dissolved in methanol (4mL), ammonium chloride (0.82 g, 15.3 mmol) was added, and the resultant mixture was stirred overnight at room temperature. The mixture was filtered and the methanol was removed in vacuo. The resulting oil was cooled to -78 C to form a solid and washed by diethyl ether (3 mL). The solid was filtered, warmed to ambient temperature and dried in vacuo to givedi ethoxyacetamidine hydrochloride (1.64 g, 58 %, 2 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6): 9.15(br, 4 H), 5.29 (s, 1H), 3.61 (q, 4 H, J = 6.8 Hz), 1.18 (t, 6 H, J = 6.8 Hz).

The synthetic route of 6136-93-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hattori, Yohei; Nishikawa, Michihiro; Kusamoto, Tetsuro; Kume, Shoko; Nishihara, Hiroshi; Chemistry Letters; vol. 43; 7; (2014); p. 1037 – 1039;,
Nitrile – Wikipedia,
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Related Products of 21803-75-8, 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. 21803-75-8, name is 4-Amino-3-chlorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

i. 3-Chloro-4-dibenzylamino-benzonitrile, 2 To a solution of 4-amino-3-chlorobenzonitrile (1.0 g, 6.56 mmol, 1 eq) and benzyl bromide (3.12 mL, 26.2 mmol, 4.0 eq) in dry DMF (10 mL) was added at rt NaH (1.31 g, 32.8 mmol, 5 eq) portionwise under Ar (g). The reaction mixture was stirred at rt overnight, and was subsequently partitioned with H2O (30 mL) and extracted with EtOAc (5*20 mL) and CH2Cl2 (20 mL). The combined organic extracts were dried over MgSO4 and the solvent was removed in vacuo. The residue was further purified by silica gel column chromatography with hexane/EtOAc (1:0-9:1) to furnish 2 as a white solid (2.09 g, 96%). 1H NMR (400 MHz, CDCl3) deltaH: 7.68 (d, J=2.0 Hz, 1H), 7.28-7.37 (m, 6H), 7.26 (d, J=2.5 Hz, 5H), 6.92 (d, J=8.5 Hz, 1H), 4.34 (s, 4H). MS (ES+) 355.1 (100%, [M+Na]+).

The chemical industry reduces the impact on the environment during synthesis 4-Amino-3-chlorobenzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; KARUS THERAPEUTICS LIMITED; Shuttleworth, Stephen Joseph; Silva, Franck Alexandre; US2013/109688; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 89001-53-6, name is 2-Methyl-4-nitrobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C8H6N2O2

(b) Synthesis of 4-amino-2-methylbenzonitrile Tin chloride dihydrate (18.5 g, 82.0 mmol) was added to a solution of 2-methyl-4-nitrobenzonitrile (3.80 g, 23.4 mmol) in ethanol (140 ml), and the resulting mixture was stirred for 3 hours under refluxing conditions. After completion of the reaction, the solvent was distilled off and the resulting residue was diluted with ethyl acetate and washed with a saturated aqueous sodium hydrogencarbonate solution. After the precipitate obtained during the washing was filtered by the use of Celite, the filtrate was extracted with ethyl acetate and the extract solution was dried over magnesium sulfate and filtered. The filtrate was concentrated to obtain 4-amino-2-methylbenzonitrile (2.89 g, 94%).

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 89001-53-6.

Reference:
Patent; Sumitomo Pharmaceuticals Company, Limited; EP1500643; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 70591-86-5, These common heterocyclic compound, 70591-86-5, name is 3-Bromobenzoylacetonitrile, 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 IV-34 3-(3-bromophenyl)-5-isoxazolamine To a solution of 3-(3-bromophenyl)-3-oxopropanenitrile (1.12 g; 5.00 mmol; Note 1) in EtOH (20 mL) was added a solution of hydroxylamine hydrochloride (1.74 g; 25 mmol) and NaOAc (2.46 g; 30 mmol) in water (20 mL). The mixture was heated under reflux for 1 h, cooled and concentrated in vacuo. The residue was slurried in 1N NaOH and extracted with Et2O (*1). The organic layer was washed (water, brine), dried over Na2SO4 and concentrated in vacuo affording the title compound as a pale yellow solid which was used without further purification. LC/MS (method B) 2.21 min, m/z 239, 241 (Br isotopes).

The synthetic route of 70591-86-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Smithkline Beecham Corporation; US2011/124559; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 327056-73-5, name is 3-Chloro-5-fluorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 3-Chloro-5-fluorobenzonitrile

Step 3: 3-Chloro-5-{[5-chloro-l-(4-methoxybenzyl)-lH-l,2,3-benzotriazol-4- yl]oxy}benzonitrile; A stirred suspension of 5 -chloro-l-(4-methoxybenzy I)- IH- 1,2, 3 -benzotriazol-4-ol (0.050 g, 0.173 mmol), 3-fluoro-5-chloro-benzonitrile (0.081 g, 0.518 mmol) and cesium carbonate (0.068 g, 0.207 mmol) in NMP (1.5 mL) was heated at 1400C for 72 hours. The reaction mixture was then quenched with aqueous ammonium chloride (25 mL) and extracted with dichloromethane (2 x 100 mL). The combined extracts were concentrated under reduced pressure. The resulting residue was subjected to reverse phase chromatography (5-95% MeCN/H2theta, 0.1% TFA). The product fractions were combined and extracted with dichloromethane (2 x 100 mL). The combined extracts were dried over MgSO4, filtered and concentrated under reduced pressure to yield the title product. lH NMR (DMSO dbeta) delta 7.90- 7.88(m, IH), 7.80(s, IH), 7.79-7.75(m, IH), 7.60-7.55(m, 2H), 7.40-7.35(d, J-6.9Hz, 2H), 6.95- 6.88 (m, 2H), 5.80(s, 2H), 3.71(s, 3H).

According to the analysis of related databases, 327056-73-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK & CO., INC.; WO2008/76223; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 51762-67-5, name is 3-Nitrophthalonitrile, 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 51762-67-5, Application In Synthesis of 3-Nitrophthalonitrile

General procedure: 2.60g (15.00mmol) 3-nitrophthalonitrile or 4-nitrophthalonitrile and 2.39g (15.50mmol) 2,6-dimethoxyphenol were dissolved in 30mL anhydrous dimethylsulfoxide (DMSO). After stirring for 15min, finely ground 5.39g (39mmol) anhydrous K2CO3 was added to this solution. The reaction mixture was stirred at 25C for 72h under nitrogen atmosphere. Then the mixture was poured into ice-water. The precipitated white product was filtered off, washed with water, and then dried in vacuum at 50C. The crude product was purified by column chromatography using silica gel eluting with chloroform (CHCl3).

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-Nitrophthalonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Pi?kin, Mehmet; Polyhedron; vol. 104; (2016); p. 17 – 24;,
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859855-53-1, name is 3-Amino-4-fluorobenzonitrile, 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. Recommanded Product: 3-Amino-4-fluorobenzonitrile

3-amino-4-fluorobenzonitrie (9.82 g, 72.1 mmol) was dissolved in acetonitrie to give a pale yellow solution. NBS (13.5g, 75.7 mmol) was added in portions; the reaction mixture tumed brown-blackish but remained a soution. After the completion of the reaction was confirmed by TLC and HPLC, silica gel was added to the reaction mixture and the solvent was evaporated under reduced pressure. The crude product was leaded on a CombiFlash column (330 g) and the product was eluted with hexanes/ethyl acetate (0 – 15% gradient). The clean fractions were combined to give 9.63 g (62%) of a yellowish off-white solid. More product was found in mixed fractions which were discarded. 1H NMR (300 MHz, dmso) 3 7.57 (d, J = 10.9 Hz. 1H). 7.17 (d. J= 8.7 Hz. 1H). 5.85 (s br. 2H); MS (ES) 213/215 (M-H).

The synthetic route of 859855-53-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RIGEL PHARMACEUTICALS, INC.; MCMURTRIE, Darren; KOLLURI, Rao; MASUDA, Esteban; TSO, Kin; ALVAREZ, Salvador; HECKRODT, Thilo; HOLLAND, Sacha; KELLEY, Ryan; DUNCTON, Matthew; SINGH, Rajinder; WO2014/89112; (2014); A1;,
Nitrile – Wikipedia,
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Synthetic Route of 64248-62-0, 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. 64248-62-0 name is 3,4-Difluorobenzonitrile, 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.

3,4-difluorobenzonitrile (2.500 g, 17.973 mmol), titanium isoproxoxide (6.917 mL, 23.364 mmol) and ethylmagnesium bromide (1.00 M solution in THF, 41.337 mL, 41.337 mmol) was dissolved in 2-methoxy-2-methylpropane (MTBE, 30 mL), at -20 C and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture borontrifluoride diethyl etherate (4.436 mL, 35.945 mmol) was added and further stirring at room temperature for 3 hours, then, at room temperature, sodium hydroxide (3.00 M solution in water, 17.973 mL, 53.918 mmol) was added and the reaction was terminated by stirring for 30 minutes. The reaction mixture was filtered through a pad of celite to remove the solid. Water was poured into the filtrate and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was purified by column chromatography (SiO2, 40 g cartridge; methanol / dichloromethane = 5% to 30%) and concentrated to give the title compound (0.822 g, 27.0%) as a light yellow liquid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,4-Difluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; Chong Kun Dang Co., Ltd.; Kim, Yoon Tae; Lee, Chang Sik; Oh, Jung Taek; Song, Hey Sung; Choe, Jin; Lee, Jae Young; (210 pag.)KR2017/43091; (2017); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts