Category: Pyrazines

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. 3149-28-8, name is 2-Methoxypyrazine, A new synthetic method of this compound is introduced below., 3149-28-8

First, in a three-neck flask, 11.30 g of 2-methoxypyrazine and 200 mL of diethylether were put, and a dibutyl ether solution (2.1 mol/L) of phenyl lithium was dropped thereto while the mixture was cooled down with ices and stirred under a nitrogen atmosphere, and stirred to be reacted for 20 hours. After the reaction, water was added to the reaction solution, and an organic layer was extracted with ethyl acetate. The obtained organic layer was washed with water, and dried with magnesium sulfate. Magnesium sulfate was removed by filtration and the solvent was distilled off. The obtained residue was refined with a column chromatography using dichloromethane as a development solvent, so that 2-phenyl-3-methoxypyrazine was obtained (light yellow powder, yield: 12%).

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; Semiconductor Energy Labratory Co., Ltd.; US2008/312437; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 5521-58-4, name is 5-Methylpyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., 5521-58-4

[0386] A mixture of 5-methylpyrazine-2-carboxylic acid (2.76 g, 20 mmol) and oxalyl chloride (1.83 mL, 2.66 g, 21 mmol) in methylene chloride (40 mL) was treated with N,N-dimethylformamide (0.5 mL), and the mixture was stirred at 25 C. for 1 h. The mixture was filtered, and the filtrate was concentrated in vacuo to give an oily solid. The solid was dissolved in acetone (120 mL) at 0 C. and then sodium azide (1.03g, 20 mmol) in water (50 mL) was added dropwise. After the addition was complete, stirring was continued at 0 C. for 30 min. The mixture was then poured into ice cold water (100 mL) and extracted with methylene chloride (3¡Á100 mL). The combined organic extracts were washed with water (1¡Á100 mL), a mixture of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution (1:1, 1¡Á100 mL), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo to give 5-methyl-pyrazine-2-carbonyl azide (1.46 g, 45%) as a tan solid. The 5-methyl-pyrazine-2-carbonyl azide (500 mg, 3.07 mmol) was combined with benzyl alcohol (0.63 mL, 663 mg, 6.14 mmol) at 25 C. The mixture was then slowly heated on an oil bath to 90 C., upon which gas was violently evolved. The oil bath temperature was maintained until gas evolution ceased. The oil bath temperature was raised to 120 C. and stirring was continued for 10 min at that temperature. The mixture was cooled and triturated with diethyl ether/hexanes (1:4) to give (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (438 mg, 58%) as a yellow solid. The (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (500 mg, 2.2 mmol) and 10% palladium on carbon (212 mg) were mixed in ethanol (30 mL). The reaction vessel was flushed with hydrogen, and the mixture was stirred at 25 C. for 1 h under hydrogen (1 atm). The excess hydrogen was evacuated from the reaction vessel, and the mixture was filtered through a pad of celite. Concentration of the filtrate in vacuo gave 2-amino-5-methylpyrazine (183 mg, 76%) as a tan solid which was used without further purification. [0387] A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionic acid (prepared as in Example 60, 263 mg, 0.73 mmol) and triphenylphosphine (250 mg, 0.95 mmol) in methylene chloride (5.0 mL) cooled to 0 C. was treated with N-bromosuccinimide (167 mg, 0.95 mmol) in small portions. After the complete addition of N-bromosuccinimide, the reaction mixture was allowed to warm to 25 C. over 30 min. The bright orange reaction mixture was then treated with 2-amino-5-methylpyrazine (160 mg, 1.46 mmol) and 2,6-lutidine (0.36 mL, 2.92 mmol). The resulting reaction mixture was stirred at 25 C. for 4 h. The reaction mixture was then diluted with methylene chloride (25 mL) and was successively washed with a 10% aqueous hydrochloric acid solution (1¡Á20 mL), a saturated aqueous sodium bicarbonate solution (1¡Á20 mL) and water (1¡Á20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 hexanes/ethyl acetate to 3/7 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-methyl-pyrazin-2-yl)-3-(4-oxo-cyclohexyl)-propionamide (158 mg, 48%) as a white foam: [alpha]23589=-41.52 (c=0.33, chloroform); EI-HRMS m/e calcd for C20H21Cl2N3O4S (M+H)+ 450.1249, found 450.1253.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Corbett, Wendy Lea; Grimsby, Joseph Samuel; Haynes, Nancy-Ellen; Kester, Robert Francis; Mahaney, Paige Erin; Racha, Jagdish Kumar; Sarabu, Ramakanth; Wang, Ka; US2003/225283; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-18-0, A common compound: 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

S-Amino–chloro-S-methoxy-pyrazine-?-carboxylic acid methyl ester [00442]Methyl 3-amino-5,6-dichloropytauazinoate (1.1 g, 5 mmol) was dissolved in 200 mL of boiling anhydrous methanol containing metallic sodium (115 mg, 5 mmol). The product which separates on cooling, is filtered, washed with water and methanol and dried to give 1.Og (92%) of methyl S-amino-S-methoxy–chloro-pyrazinoate which was recrystallized from acetonitrile. MP. 255-257 C. [00443J 1H NMR (DMSO-rf?, 400MHz): delta 7.61 Qm, 2H, NH2, exchangeable with D2O), 3.97 (s, 3H), 3.80 (s, 3H).

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, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARDEA BIOSCIENCES INC.; WO2009/89263; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-01-1, Adding some certain compound to certain chemical reactions, such as: 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, 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 1458-01-1.

General procedure: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

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 1458-01-1.

Reference:
Article; Buckley, Benjamin J.; Majed, Hiwa; Aboelela, Ashraf; Minaei, Elahe; Jiang, Longguang; Fildes, Karen; Cheung, Chen-Yi; Johnson, Darren; Bachovchin, Daniel; Cook, Gregory M.; Huang, Mingdong; Ranson, Marie; Kelso, Michael J.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 24; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, 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. 33332-29-5 name is 2-Amino-5-chloropyrazine, 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.

General procedure: A magnetically stirred solution of xanthate (2.0 equiv) and pyrazine (1.0 equiv) in 1, 2-dichloroethane (1.0mmol/mL according to the xanthate) was refluxed for 15min under a flow of nitrogen. Then dilauroyl peroxide (DLP) was added portionwise (20mol % according to the xanthate) every hour until total consumption of one substrate. The reaction mixture was then cooled to room temperature and the solvent was evaporated under reduced pressure. Unless otherwise specified, the crude product was purified by flash chromatography on silica gel.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-5-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Article; Huang, Qi; Qin, Ling; Zard, Samir Z.; Tetrahedron; vol. 74; 40; (2018); p. 5804 – 5817;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1,Some common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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.

5-(Cyclopropylmethoxy)pyrazine-2-carboxylic acid A solution of 5-chloropyrazine-2-carboxylic acid (1.00 g, 6.31 mmol), cyclopropyl carbinol (1.00 mL, 12.4 mmol) and potassium tert-butoxide (2.00 g, 17.8 mmol) in dimethylformamide (20.0 mL) is heated at 100 C. for 3 hours. The reaction is cooled to room temperature, quenched with 1M hydrochloric acid. The mixture is extracted with ethyl acetate and isopropyl alcohol/chloroform (1/10), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (1.10 g, 90%) as a grayish solid. This acid is used directly without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Chloropyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; GREEN, Steven James; HEMBRE, Erik James; MERGOTT, Dustin James; SHI, Yuan; WATSON, Brian Morgan; WINNEROSKI, JR., Leonard Larry; US2014/371212; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

41270-66-0, 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. 41270-66-0, name is 5-Chloro-2,3-diphenylpyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To the stirred mixture of 5-chloro 2-3 diphenyl pyrazine (100 g, 0.375 mol) & 4-isopropyl amino butane-1-ol (172.17 g, 1.31 mol) was added at room temperature. The resultant reaction mixture was heated at 180-185C and maintain at same temperature for 24 hrs. After completion of reaction by HPLC analysis, cool the reaction mass and diluted it with ethyl acetate (1000 ml), purified water (1500 ml) and product was extracted : in ethyl acetate further aqueous layer was rewashed with ethyl acetate (500 ml). After combining the both ethyl acetate layers, wash it with 5% sodium bicarbonate (1000 ml) to remove the hydroxyl impurity formed during the reaction followed by washing of 10% sodium chloride solution (1000 ml). Ethyl acetate layer was concentrated under reduced pressure to obtain thick syrup of compound (4). Obtained thick syrup was diluted with ethyl acetate (20 ml) and n-heptane (500 ml) was added to the diluted mass and stirred for 60-90 min. the resultant isolated solid was filtered and washed with n-heptane (100 ml), suck dried and dried the solid under vacuum at 35-40 C for 3-4 hrs. [Yield = 95.0 g; Purity (HPLC) = 91.5%]

The synthetic route of 5-Chloro-2,3-diphenylpyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEGAFINE PHARMA (P) LTD.; MATHAD VIJAYAVITTHAL THIPPANNACHAR; DODDAPPA PRALHAD ANEKAL; KARDILE PRITESH BHIMRAJ; PADAKI SANTHOSH AMBADAS; GAIKWAD BAPUSAHEB SHRIHARI; SHINDE GORAKSHANATH BALASAHEB; (63 pag.)WO2017/42828; (2017); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

41270-66-0, 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. 41270-66-0, name is 5-Chloro-2,3-diphenylpyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Trimethylamine (33% ethanol solution, 358 g, 2.0 mol) was added to ethyl acetate (1.3 L) of 5-chloro-2,3-diphenylpiperazine (266 g, 1.0 mol)And stirred at room temperature for 48 hours.A large number of solids are present.filter,The solid was washed with ethyl acetate (2 x 50 mL)Dried in high vacuum to give 283.5 g of a white solid,The yield was 87%.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Suzhou Guohang Pharmaceutical Technology Co., Ltd.; Mei, Desheng; (11 pag.)CN106467496; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19745-07-4, 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 19745-07-4 as follows.

3.0 g of 2,5-dichloropyrazine,880 mg of sodium hydride (60percent, oil)And 50 mL of NMP,2.3 g of benzyl alcohol was added under ice cooling.The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 5 hours.Water was added to the resulting reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate,And concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography,3.1 g of Intermediate 1 represented by the following formula was obtained.Intermediate 1

According to the analysis of related databases, 2,5-Dichloropyrazine, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SUMITOMO CHEMICAL COMPANY LIMITED; SAKAMOTO, EMIKO; NISHIMURA, SHINYA; (242 pag.)JP2018/24669; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 19745-07-4, name is 2,5-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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. 19745-07-4

To a solution of NaH (0.755 g> 18.88 mmol) in THF (55 mL) was added benzyl mercaptan (1.5 mL, 12.68 mmol) at o ¡ãC. The reaction mixture was diluted with THF (20 mL) and stirred at o ¡ãC for 10 minutes. Then a solution of 2,5-dichloropyrazine (1.370 mL, 13.42 mmol) in THF (10 mL) was added dropwise. The reaction mixture was stirred at o ¡ãC for 1 hour, then warmed to room temperature and stirred for 16 hours. The reaction mixture was cooled to o ¡ãC, MeOH (1 mL) was added carefully and stirred for 5 minutes. Water (20 mL), then DCM (150 mL) was added and the biphasic mixture was passed through a phase separator. The organic phase was concentrated in vacuo. The crude product was purified by chromatography on silica gel (40 g column, 0-3percent EtOAc/isohexane) to afford the title compound (2.373 g, 72 percent) as a clear yellow oil. NMR (DMSO-d6) delta 8.68 (d, J = 1.5 Hz, lH), 8.49 (d, J = 1.5 Hz, lH), 7.43 – 7.39 (m, 2H), 7.34 – 7.29 (m, 2H), 7.28 – 7.23 (m, lH), 4.46 (s, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19745-07-4, its application will become more common.

Reference:
Patent; INFLAZOME LIMITED; COOPER, Matthew; MILLER, David; MACLEOD, Angus; VAN WILTENBURG, Jimmy; THOM, Stephen; ST-GALLAY, Stephen; SHANNON, Jonathan; (352 pag.)WO2019/8025; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem