Month: June 2021

Application of 53312-82-6, A common heterocyclic compound, 53312-82-6, name is 4-Amino-2-bromobenzonitrile, molecular formula is C7H5BrN2, 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 a stirred mixture of 4-amino-2-bromobenzonitrile (2.00 g, 10.2 mmol), cyclopropyl boronic acid (1,18 g, 13.7 mmol) and K3PO4 (3.23 g, 15.2 mmol) in the mixed solvents of EtOH/H2O/toluene (2 mL/2 mL/12 mL) under nitrogen was added PdCl2(PPh3)2 (0.72 g, 1.03 mmol). This mixture was heated at 800C for 19 h and cooled to room temperature. Next, the mixture was diluted with 150 mL of EtOAc and filtered through a pad of silica gel topped with a layer of celite. This pad was further rinsed with EtOAc (2 x 100 mL). The filtrate was washed with 25 mL of brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude amine. The crude amine was purified by an ISCO auto flash chromatographer using 12O g silica gel column, eluted with hexanes/CH2Cl2 solvents in a 25 min 50% to 100% gradient elution to give 0.75 g of Preparation 4OA as a white solid in 47% yield. [00428] HPLC: 1.55 min (RT) (Chromolith SpeedROD column 4.6 x 50 mm, 10- 90% aqueous MeOH over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z=159 [M+H]+. 1H NMR of 4-amino-2- cyclopropyl-benzonitrile (400 MHz, CDCl3) delta ppm 7.34 (d, J=8.31 Hz, 1 H) 6.44 (dd, J=8.31, 2.27 Hz, 1 H) 6.12 (d, J=2.01 Hz, 1 H) 4.01 (s, 2 H) 2.13-2.24 (m, 1 H) 1.02- 1.12 (m, 2 H) 0.68-0.76 (m, 2 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; BRISTOL-MYERS SQUIBB COMPANY; WO2009/3077; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 950596-58-4, name is 2-Amino-4,5-bis(2-methoxyethoxy)benzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 2-Amino-4,5-bis(2-methoxyethoxy)benzonitrile

(f) Erlotinib free base:; To 2-amio-4,5-bis(2-methoxyethoxy)benzonitrile (4.57g, 0.0172moles) was added toluene (30ml), N’-(3-ethynylphenyl) N,N-dimethyl formamidine (3.44g, 0.0172moles) and acetic acid (0.5ml) refluxed the reaction mixture for about 4hrs cooled the reaction mass to room temperature, toluene layer was separated washed with water and chilled toluene layer to yield crude erlotinib and which was further recrystallized from a polar solvent such as methanol to get pure off- white crystalline compound(3g) having mp 149-153 0C.

The synthetic route of 950596-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VITTAL MALLYA SCIENTIFIC RESEARCH FOUNDATION; WO2007/138612; (2007); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 64248-63-1, The chemical industry reduces the impact on the environment during synthesis 64248-63-1, name is 3,5-Difluorobenzonitrile, I believe this compound will play a more active role in future production and life.

3-Fluoro-5-methoxybenzoic Acid In a 250 ml round bottom flask equipped with stir bar added 3,5-Difluorobenzonitrile (4.2 g, 30.4 mmol), sodium methoxide (10.4 ml, 45.6 mmol, 25% methanol) and dimethylformamide (40 ml). Stirred the resulting reaction mixture at room temperature, overnight. The reaction mixture was concentrated in-vacuo and residue was dissolved in dichloromethane (200 ml). The organic phase was washed sequentially with water (150 ml) and brine (150 ml), dried (sodium sulfate) and concentrated in-vacuo. The crude residue was purified on silica gel using 10% diethyl ether in hexanes to isolate 3-Fluoro-5-methoxybenzonitrile (1.63 g) as a white solid.

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, 3,5-Difluorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Wagenen, Bradford Van; Stormann, Thomas M.; Moe, Scott T.; Sheehan, Susan M.; McLeod, Donald A.; Smith, Daryl L.; Isaac, Methvin Benjamin; Slassi, Abdelmalik; US2003/55085; (2003); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 134997-74-3, name is 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile, 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 134997-74-3, Quality Control of 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile

To a stirred solution of 3-oxo-3,4-dihydro-2H-benzo[b][1 ,4]oxazine-6-carbonitrile (3.30 g, 1 9.0 mmol) in N,N-dimethylformamide (35 mL) was added sodium hydride (758 mg, 1 9 mmol, 60% dispersion in mineral oil) and iodoethane (3.84 g, 25 mmol, 1 .97 mL) at 0 C. The mixture was warmed to 20 00. After 3 h, the mixture was cooled to 0 C, quenched by addition of water (50 mL), and extracted with ethylacetate (60 mL x 4). The combined organic phases were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give crude product that was purified by chromatography (silica, petroleum ether : ethyl acetate 50:1 to 5:1) to give 4-ethyl-3-oxo-3,4-dihydro-2H-benzo[b][1 ,4]oxazine-6-carbonitrile (1 .30 g, 6.43 mmol, 34 %) as a white solid. 1H NMR (400 MHz, CDC3) O 7.25 (dd, J 1.8, 8.3 Hz, 1 H), 7.17 (d, J 1 .8 Hz, 1 H), 6.98 (d, J8.3 Hz, 1H), 4.62 (s, 2H), 3.93 (q, J 7.2 Hz, 2H), 1.23 (t, J 7.2 Hz, 3H); LOMS (ESI) m/z 203.1 [M÷H]÷.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; YUMANITY THERAPEUTICS; LUCAS, Matthew; LE BOURDONNEC, Bertrand; WRONA, Iwona; PANDYA, Bhaumik; TIVITMAHAISOON, Parcharee; OZBOYA, Kerem; VINCENT, Benjamin; TARDIFF, Daniel; PIOTROWSKI, Jeff; SOLIS, Eric; SCANNEVIN, Robert; CHUNG, Chee-Yeun; ARON, Rebecca; RHODES, Kenneth; (489 pag.)WO2018/81167; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 16588-02-6, name is 2-Chloro-5-nitrobenzonitrile, 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 16588-02-6, Recommanded Product: 16588-02-6

A mixture of 3 -methyl- IH-1, 2;4-triazole (6.83 g, 82 mmol), 2- chloro-5-mtrobenzomtrile (15 g, 82 mmol), and potassium carbonate (34.1 g, 246 mmol) in anhydrous acetonitrile (200 mL) was heated at 70 0C for 16 h. The dark brown reaction mixture was allowed to cool to rt and was poured into water (500 mL). The aqueous mixture was extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified using silica gel chromatography (40-100% ethyl acetate/hexane, linear gradient) to afford 2-(3-methyl~lH-l,2,4-triazol-l-yl)-5- nitrobenzonitrile (10.9 g, 58 % yield). LC-MS (M+H)+ – 230.1. 1H NMR (500 MHz, chloroform-D) delta ppm 2.53 (s, 3 H) 8.10 (d, J-9.16 Hz, 1 H) 8.56 (dd, J-9.16, 2.44 Hz, 1 H) 8.68 (d, J-2.44 Hz, 1 H) 8.93 (s, 1 H).

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; BRISTOL-MYERS SQUIBB COMPANY; MARCIN, Lawrence, R.; THOMPSON, Lorin, A., III; BOY, Kenneth, M.; GUERNON, Jason, M.; HIGGINS, Mendi, A.; SHI, Jianliang; WU, Yong-Jin; ZHANG, Yunhui; MACOR, John, E.; WO2010/83141; (2010); 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. 6609-57-0, name is 2-Ethoxybenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 2-Ethoxybenzonitrile

Preparation 7 2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzonitrile Commercially available 2-ethoxybenzonitrile (25 g, 0.17 Mol) was added dropwise to an ice cooled mixture of chlorosulfonic acid (50.8 mL, 0.765 Mol) and thionyl chloride (12.4 mL, 0.17 Mol) so as to keep the temperature below 10 C. The reaction was then stirred at ambient temperature for 18 h before being poured onto ice/water. This mixture was stirred 1 hr before the precipitated material was filtered off. The resultant solid was dissolved in acetone (300 mL) and triethylamine (25 mL, 0.179 Mol) was added followed by a slow addition of N-ethylpiperazine (25 mL, 0.198 Mol).

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 6609-57-0.

Reference:
Patent; Dunn, Peter James; Dunne, Catherine; US2002/13464; (2002); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 4475-95-0, name is 2-Amino-2-methylbutanenitrile, molecular formula is C5H10N2, 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

5.00 g (50.94 mmol) of 2-amino-2-methylbutanonitrile [synthesis described in: Lonza AG, U.S. Pat. No. 5,698,704 (1997); Deng, S. L. et al. Synthesis 2001, 2445; Hjorringgaard, C. U. et al. J. Org. Chem. 2009, 74, 1329; Ogrel, A. et al. Eur. J Org. Chem. 2000, 857] were initially charged in 50 ml of THF and 6.5 ml of water, 21.83 g (157.92 mmol) of potassium carbonate were added and, at 0 C., 7.9 ml (56.04 mmol) of benzyl chlorocarbonate (benzyl chloroformate) were added. After the addition of 8 ml of THF and 3 ml of water, the reaction mixture was stirred overnight, slowly warming to RT. Water was then added, and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in diethyl ether and precipitated with petroleum ether. The product was filtered off and the solid was washed with a little petroleum ether and dried under high vacuum. This gave 11.35 g of the target compound (93% of theory, purity 97%). LC-MS (Method 5): Rt=0.97 min MS (ESpos): m/z=233 (M+H)+1H NMR (400 MHz, DMSO-d6): delta=0.95 (t, 3H), 1.51 (s, 3H), 1.75-1.95 (m, 2H), 5.07 (s, 2H), 7.30-7.43 (m, 4H), 7.88-8.03 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4475-95-0, its application will become more common.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; VAKALOPOULOS, Alexandros; VALOT, Gaelle; LINDNER, Niels; FOLLMANN, Markus; STASCH, Johannes-Peter; WUNDER, Frank; MARQUARDT, Tobias; DIETZ, Lisa; LI, Volkhart Min-Jian; (74 pag.)US2017/233345; (2017); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts