Month: September 2021

Some common heterocyclic compound, 5653-62-3, name is 2,3-Dimethoxybenzonitrile, molecular formula is C9H9NO2, 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. Safety of 2,3-Dimethoxybenzonitrile

To a solution of 1,1,1,3,3,3-hexamethyldisilazane (20 g) in dry ether (150 mL) was added 2.4M n-butyllithium in hexane (5 mL). After 10 min at room temperature, 2,3-Dimethoxybenzonitrile (16.3 g) was added in one portion and the mixture was kept at room temperature for 16 h. The reaction mixture was the poured onto excess 3N HCl. The aqueous layer was separated, basified with 50% NaOH and the product was exuacted three times with 10% methanol in methylene chloride. The combined organic extracts were dried over magnesium sulfate and the solvents removed in vacuo to afford 2,3-Dimethoxy-benzamidine as a glassy solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5653-62-3, its application will become more common.

Reference:
Patent; Neurogen Corporation; US5681956; (1997); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 14533-86-9, name is Methyl (E)-2-Cyano-3-phenylacrylate, 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. category: nitriles-buliding-blocks

General procedure: To a solution of 1 (0.10 mmol, 1.0 equiv.), [(TMEDA)Ni(o-tolyl)Cl] (1.6 mg, 0.0050 mmol, 5.0 mol %),and PMePh2 (1.9 L, 0.010 mmol, 10 mol %) in THF (1.0 mL, 0.10 M) under an argon atmosphere was added Et2Zn (1.0 M in hexanes, 0.15 mL, 0.15 mmol, 1.5 equiv) at 0 C. After being stirred the mixture at 30 C for the indicated reaction time judged by TLC analysis, the electrophile (2.0 equiv) was added tothe reaction solution at 30 C unless otherwise noted. The reaction mixture was stirred at the indicated temperature for the indicated reaction time. The reaction was quenched by the addition of sat. aq. NH4Cl.The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organiclayer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified byflash column chromatography (hexane/EtOAc or hexane/CH2Cl2/EtOAc) on silica gel to afford corresponding product.

The synthetic route of Methyl (E)-2-Cyano-3-phenylacrylate has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tsujihara, Tetsuya; Tomeba, Moriho; Ohkubo-Sato, Shigeaki; Iwabuchi, Kyoko; Koie, Rino; Tada, Natsumi; Tamura, Satoru; Takehara, Tsunayoshi; Suzuki, Takeyuki; Kawano, Tomikazu; Tetrahedron Letters; vol. 60; 42; (2019);,
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Electric Literature of 21803-75-8, 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 21803-75-8 as follows.

To a solution of phosgene (2.3 mL, 20% in toluene) in dry DCM (20 mL) was added a solution of 2-chloro-4-cyanoaniline (367 mg) and DIEA (372 mg) in dry DCM slowly. The resulting mixture was stirred at room temperature for 1 hr prior to evaporation to dryness. The residue was dissolved in DCM (10 mL) to which a solution of compound 1f (Example 1,510 mg) and DIEA (310 mg) in DCM was added. The resulting mixture was stirred overnight at room temperature. Aqueous sodium bicarbonate was added and the mixture was extracted with DCM. The organic phase was dried over MgS04 and evaporated to dryness.

According to the analysis of related databases, 21803-75-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SB PHARMCO PUERTO RICO INC; NEUROCRINE BIOSCIENCES INC; WO2005/63749; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 1255870-63-3, name is 4-Bromo-2-ethoxybenzonitrile, 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. Formula: C9H8BrNO

A suspension of 4-bromo-2-ethoxybenzonitrile (1.50 g, 6.5 mmol), hydroxylamine hydrochloride (913 mg, 13 mmol) and NaHCOs (1.365 g, 16.3 mmol) in water (1.32 mL) and EtOH (26.6 mL) is stirred in a sealed tube at 90 C for 3h. Once at RT, the product precipitated from the RM upon addition of water. The solid is filtered off under high vacuum, washing with water and some Et20. A first crop of pure title compound (947mg) was thus obtained as white solid. The filtrate is extracted with AcOEt. The organic layer is then washed twice with brine, dried over MgSO4, filtered and concentrated. The residue is purified by FC (hept AcOEt 5:5) to yield another crop of the pure title compound as a white solid (448 mg), merged with the first batch from precipitation. The title compound is obtained as a white solid (1.395 g, 83%). LC-MS A: tR = 0.53min, [M+H]+ = 259.03.

The synthetic route of 4-Bromo-2-ethoxybenzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IDORSIA PHARMACEUTICALS LTD; BOSS, Christoph; CORMINBOEUF, Olivier; FRETZ, Heinz; LYOTHIER, Isabelle; POZZI, Davide; RICHARD-BILDSTEIN, Sylvia; SIENDT, Herve; SIFFERLEN, Thierry; (160 pag.)WO2018/210992; (2018); A1;,
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Synthetic Route of 151-18-8,Some common heterocyclic compound, 151-18-8, name is 3-Aminopropanenitrile, molecular formula is C3H6N2, 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 DMF (1.6 mL) solution of 3-(2-[[3-(trifluoromethyl)phenyl]amino][1,2,4]triazolo[1,5-a]pyridin-8-yl)benzoic acid (80 mg, 0.201 mmol) obtained in Reference Example 122, 3-aminopropanenitrile (0.016 mL, 0.221 mmol), HATU (91.6 mg, 0.241 mmol), and N,N-diisopropylethylamine (0.042 mL, 0.241 mmol) was stirred for 3 hours at room temperature. Water was poured into the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off at reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized from hexane and ethyl acetate to give 68.4 mg of the titled compound (yield 76%) in solid form. Melting point: 214-215 C.1H-NMR (DMSO-d6) delta: 2.81 (2H, t, J=6.5 Hz), 3.55 (2H, q, J=6.5 Hz), 7.15-7.26 (2H, m), 7.53 (1H, t, J=8.0 Hz), 7.65 (1H, t, J=8.0 Hz), 7.89-7.97 (3H, m), 8.21 (1H, br s), 8.34-8.41 (1H, m), 8.49 (1H, t, J=1.6 Hz), 8.89 (1H, dd, J=6.7, 1.0 Hz), 8.99 (1H, t, J=5.7 Hz), 10.22 (1H, s).

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

Reference:
Patent; Takeda Pharmaceutical Company Limited; US2010/41891; (2010); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 102151-33-7, name is 3-Chloro-4-methoxybenzonitrile, 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 102151-33-7, name: 3-Chloro-4-methoxybenzonitrile

Step 1 To a solution of N,N-diethyl-4-methoxy-2-methylbenzamide (1 g, 4.52 mmol) in THF (9 ml) at -78 C. was added dropwise tert-butyllithium 1.7 M in pentane (3.19 ml, 5.42 mmol) and the solution was stirred for 0.5 h before addition of 3-chloro-4-methoxybenzonitrile (0.757 g, 4.52 mmol) in THF (9 ml). The resulting solution was warmed to rt and stirred for 16 h. The reaction mixture was quenched with water, neutralized with 1 N HCl. The precipitated solid was collected and washed with water to give 3-(3-chloro-4-methoxyphenyl)-6-methoxyisoquinolin-1-ol (1.2 g, 84% yield) as a solid after drying. MS: MS m/z 316.1 (M++1).

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-Chloro-4-methoxybenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Bristol-Myers Squibb Company; Hiebert, Sheldon; Rajamani, Ramkumar; Sun, Li-Qiang; Mull, Eric; Gillis, Eric P.; Bowsher, Michael S.; Zhao, Qian; Meanwell, Nicholas A.; Renduchintala, Kishore V.; Sarkunam, Kandhasamy; Nagalakshmi, Pulicharla; Babu, P. V. K. Suresh; Scola, Paul Michael; US2013/115190; (2013); A1;,
Nitrile – Wikipedia,
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Related Products of 3544-25-0,Some common heterocyclic compound, 3544-25-0, name is 2-(4-Aminophenyl)acetonitrile, molecular formula is C8H8N2, 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-Amino-phenyl)-acetonitrile (2 g, 15.1 mmol) and dibenzyl dicarbonate (4.33 g, 15.1 mmol) dissolved in dioxane (16 mL) are stirred for 1 hour at RT. After evaporating the solvent, the product is isolated by flash chromatography (silica gel, 4.5×25 cm, CH2Cl2/MeOH=99:1): white solid (3.82 g, 14.4 mmol; 95%); ES-MS: M-H=265.0; Rf(CH2Cl2/MeOH=95:5)=0.49; HPLC: AtRet=6.32 minutes. 1H-NMR (400 MHz, DMSO-d6): 9.82 (s, 1H, NH), 7.51-7.35 (m, 7H, aryl), 7.26 (d, 8.5 Hz, 2H, aryl), 5.15 (s, 2H, CH2), 3.95 (s, 2H, CH2).

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

Reference:
Patent; Bold, Guido; Floersheimer, Andreas; Furet, Pascal; Imbach, Patricia; Masuya, Keiichi; Schoepfer, Joseph G.; US2005/222171; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 75344-77-3, A common heterocyclic compound, 75344-77-3, name is 4-Bromo-3,5-dimethylbenzonitrile, molecular formula is C9H8BrN, 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.

Step A: 4-bromo-3.5-dimethylbenzamide To a solution of 4-bromo-3, 5- dimethylbenzonitrile (1.0 g, 4.8 mmol) in DMSO (10 ml) at 0 C was added 35% H202 (0.542 mL, 6.19 mmol) and K2C03 (1.32 g, 9.52 mmol). The resulting mixture was stirred at 20 C for2 hours and then poured into water (50 mL). The resulting solid was collected by filtration, then washed with water twice, dried in an oven to give the title compound. ?H NMR (400MHz, CD3OD) oe: 7.62 (s, 2H), 2.46 (s, 6H).

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; MERCK SHARP & DOHME CORP.; BIFTU, Tesfaye; BIJU, Purakkattle; COLLETTI, Steven, L.; DANG, Qun; DHONDI, Pawan, K.; GUDE, Candido; JOSIEN, Hubert; KAR, Nam Fung; NAIR, Anilkumar, G.; NARGUND, Ravi, P.; YANG, De-Yi; XIAO, Dong; ZHU, Cheng; WO2015/73342; (2015); A1;,
Nitrile – Wikipedia,
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Application of 326-62-5, 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.

To a solution of 2- (2-fluorophenyl) acetonitrile (5.4 g, 40 mmol) in anhydrous THF (50 mL) was added dropwise of LDA (26 mL, 52 mmol, 1.3 eq) at -78. After addition, the mixture was stirred at -78 for 0.5 h. Then methyl benzoate (6.0 g, 44 mmol, 1.1 eq) in THF (10 mL) was added slowly and stirred at RT overnight. The suspension was quenched with NH4Cl solution (30 mL) and extracted with EA. The organic phase was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 2- (2-fluorophenyl) -3-oxo-3-phenylpropanenitrile (12 g, crude) which was used directly to the next step without further purification. LC-MS: m/z 240.1 (M+H) +.

The chemical industry reduces the impact on the environment during synthesis 2-(2-Fluorophenyl)acetonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AGIOS PHARMACEUTICALS, INC.; TRAVINS, Jeremy, M.; KONTEATIS, Zenon, D.; SUI, Zhihua; YE, Zhixiong; (199 pag.)WO2018/39972; (2018); A1;,
Nitrile – Wikipedia,
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Related Products of 14618-78-1, 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. 14618-78-1 name is 4,4-Dimethoxybutanenitrile, 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.

In a 500 ml four-necked flask,Add 100 grams of tetrahydrofuran,13.0 g (0.1 mol) of 4,4-dimethoxy-n-butyronitrile,13.0 g (0.1 mol) of 2,3-dichloropropenal,0.5 g DBU,Reaction at 60 C for 4 hours,The gas phase detection 1,4-addition reaction is completed.Cool down to 25-30 C,Add 15.0 grams of potassium carbonate,25.0 grams of 17% ammonia,8.0 grams of ammonium chloride,Reaction at 50 C for 5 hours,Cool down to 20-25 C,filter,20 grams of ice water wash filter cake,dry,Obtained 13.5 g of 5-chloro-7-azaindole,The liquid phase purity is 99.7%,The yield was 88.5%.

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

Reference:
Patent; Xin Fa Pharmaceutical Co., Ltd.; Qi Yuxin; Zhang Mingfeng; Wang Sheng; Li Guangqian; Ju Lizhu; (7 pag.)CN110128421; (2019); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts