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. 313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, A new synthetic method of this compound is introduced below., Application In Synthesis of 3,5-Dichloro-6-ethylpyrazine-2-carboxamide

A mixture of 3,5-dichloro-6-ethylpyrazine-2-carboxamide (3a,503 mg, 2.29 mmol), 2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (699 mg, 2.30 mmol), DIPEA (0.78 mL, 4.56 mmol) and 1,4-dioxane (10 mL) was stirred at 110 C for 25 h. After the mixture was cooled to room temperature, saturated aqueous NaHCO3 solution was added, and the resulting slurry was extracted with CHCl3. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (CHCl3/MeOH/28% aqueous NH3=100:0:0 to90:9:1). The resulting product was washed with EtOAc, filtered and dried in vacuo at 50 C to give 9 (701 mg, 63%) as an orange solid. 1HNMR (DMSO-d6): delta 1.25 (3H, t, J=7.4 Hz), 1.43-1.59 (2H, m),1.77-1.91 (2H, m), 2.14 (3H, s), 2.20-2.72 (11H, m), 2.79 (2H, q,J=7.5 Hz), 3.64-3.75 (2H, m), 3.85 (3H, s), 6.51 (1H, dd, J=2.4, 8.8 Hz), 6.65 (1H, d, J=2.4 Hz), 7.83 (1H, d, J=1.6 Hz), 8.04 (1H, d,J=8.8 Hz), 8.12 (1H, d, J=1.6 Hz), 11.11 (1H, s); MS (ESI) m/z[M+H]+ 488.

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:
Article; Iikubo, Kazuhiko; Kurosawa, Kazuo; Matsuya, Takahiro; Kondoh, Yutaka; Kamikawa, Akio; Moritomo, Ayako; Iwai, Yoshinori; Tomiyama, Hiroshi; Shimada, Itsuro; Bioorganic and Medicinal Chemistry; vol. 27; 8; (2019); p. 1683 – 1692;,
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. 27825-21-4, name is Methyl 3-chloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C6H5ClN2O2

EXAMPLE II-23 In 15 mL of acetonitrile was dissolved 0.3 g of methyl 3-chloro-2-pyrazinecarboxylate. At an ice-cooled temperature, 10% fluorine gas (a fluorine gas diluted with nitrogen gas) was introduced at a rate of 45 ml per minute for a period of 18 minutes. Then, while elevating the temperature from the ice-cooled temperature to room temperature, nitrogen gas was introduced for one hour, and the reaction product was concentrated under reduced pressure. The oily product thus obtained was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=10:1] to obtain 0.03 g of methyl 3-chloro-6-fluoro-2-pyrazinecarboxylate as a colorless oily product. IR (neat) cm-1: 1736 1H-NMR (CDCl3) delta: 4.04(3H,s), 8.43(1H,d,J=8.3 Hz)

According to the analysis of related databases, 27825-21-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Toyama Chemical Co., Ltd.; US2003/130213; (2003); 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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 2-Bromo-5H-pyrrolo[2,3-b]pyrazine

To a solution of 2-bromo-5H-pyrrolo [2, 3-b] pyrazine (1.94 g, 9.8 mmol) in DMF (20 mL) was added sodium hydride (60, 525.3 mg, 13.13 mmol) in an ice bath. The mixture was stirred at this temperature for 30 min and then SEMCl (2.26 mL, 12.6 mmol) was added. The mixture was stirred at rt overnight. The reaction mixture was quenched with water (40 mL) . The resulting mixture was extracted with DCM (30 mL × 3) . The combined organic layers were dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 7/1 to give a light yellow oily product (2.40 g, 75.0) .[0819]MS (ESI, pos. ion) m/z: 328.15 [M+1]+.

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 875781-43-4.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; LIU, Bing; ZHANG, Yingjun; CHENG, Changchung; HUANG, Jiuzhong; BAI, Shun; REN, Xingye; LI, Zhi; ZHOU, Youbai; (368 pag.)WO2016/615; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 69214-33-1, 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 69214-33-1 as follows.

8-chloroimidazo [1,2-a] pyrazine (1.07 g, 7 mmol) was dissolved in 15 mL glacial acetic acid, and liquid bromine (1.12 g, 7 mmol) was slowly added dropwise under an ice bath.Remove the ice bath after the addition and stir overnight at room temperature.TLC showed that the reaction was complete. Add 30 mL of saturated sodium sulfite solution and extract with ethyl acetate (30 mL * 3).The organic phases were combined and washed with 20 mL of saturated brine.Dry over anhydrous sodium sulfate, concentrate,Separation through a silica gel column gave 1.33 g of a pale yellow solid with a yield of 82%.

According to the analysis of related databases, 69214-33-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Shenzhen Tajirui Bio-pharmaceutical Co., Ltd.; Wang Yihan; Xing Qingfeng; Ai Yixin; (85 pag.)CN110272426; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, belongs to pyrazines 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 136927-64-5, Safety of 1-Chloropyrrolo[1,2-a]pyrazine

To a mixture of 1 (1.0 g, 4.6 mmol) and 580 mg of 2 (580 mg, 3.8 mmol) was added 1.7 ml of Hunig?s base (9.5mmol). The resulting mixture was stirred at 130 C. for 3 h. After the mixture was cooled down to room temperature, 200 ml of isopropanol/chloroform (1:2) was added, and the organics were washed with saturated aqueous NaHC03 (2×20 ml)and brine (2×50 ml). The organics were dried over MgS04 and concentrated under reduced pressure. The residue was purified via flash column chromatography on silica gel (0-10% MeOH in EtOAc) to get the desired product 3 as a brown powder (700 mg, 46%).

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; ChemoCentryx, Inc.; Fan, Junfa; Krasinski, Antoni; Lange, Christopher W.; Lui, Rebecca M.; McMahon, Jeffrey P.; Powers, Jay P.; Zeng, Yibin; Zhang, Penglie; US2014/154179; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 122-05-4,Some common heterocyclic compound, 122-05-4, name is Pyrazine-2,5-dicarboxylic acid, molecular formula is C6H4N2O4, 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.

Pyrazine-2,5-dicarboxylic acid 2 was prepared according to the procedure of Schut et al. Compound 2 was esterified with methanol and hydrogen chloride gas to give dimethyl pyrazine-2,5-dicarboxylate 3. A suspension of 3 (2.0 g, 10.19 mmol) in methanol (250 mL) was stirred as a solution of sodium hydroxide (408 mg in 10.1 mL of water) was added. The mixture was then stirred for another 16 h. The solvent was removed under reduced pressure and the resulting solid was dissolved in water and filtered. The filtrate was acidified with 1N HCl, and the precipitated product was collected by filtration and dried under vacuum to give 4, 1.36 g, 73% yield of product as a white solid.

The synthetic route of 122-05-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Agyin, Joseph K.; Santhamma, Bindu; Roy, Sudipa S.; Bioorganic and Medicinal Chemistry Letters; vol. 23; 23; (2013); p. 6455 – 6458;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 63744-22-9,Some common heterocyclic compound, 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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.

(R)-(4-(4-((6-Bromoimidazo[1,2-a]pyrazin-8-yl)amino)phenyl)morpholin-2-yl)methanol XVII In a 250 mL round bottom flask equipped with a condenser was placed 6,8-dibromoimidazo[1,2-a]pyrazine (2000 mg, 7.22 mmol) and added 30 mL isopropanol followed by N,N-diisopropylethylamine (2.52 ml, 14.44 mmol) and (R)-(4-(4-aminophenyl)morpholin-2-yl)methanol (1504.12 mg, 7.22 mmol). The reaction was heated to reflux (oil bath 95 C.) overnight. The reaction was cooled and precipitates were collected by filtration and washed with isopropanol followed by hexanes to give the desired compound XVII.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6,8-Dibromoimidazo[1,2-a]pyrazine, its application will become more common.

Reference:
Patent; Blomgren, Peter A.; Currie, Kevin S.; Kropf, Jeffrey E.; Lee, Seung H.; Lo, Jennifer R.; Mitchell, Scott A.; Schmitt, Aaron C.; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; US2015/175616; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 74290-65-6, 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. 74290-65-6 name is 3-Bromo-5-methylpyrazin-2-amine, 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.

(b) 2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)). The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation. Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75%), m.p. 67-69 C.; mass spectrum (+ve CI): 140 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-5-methylpyrazin-2-amine, and friends who are interested can also refer to it.

Reference:
Patent; Zeneca Limited; US5866568; (1999); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 912773-21-8, 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. 912773-21-8 name is 2-Bromo-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.

A mixture of 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)-2-[(lS)-2,2,2-trifluoro-l-methyl-ethoxy]pyridine (600 mg, 1.89 mmol), 2-bromo-5- chloro-pyrazine (329.39 mg, 1.7 mmol), Pd(dppf)Cl2 (207.67 mg, 0.28 mmol) and CS2CO3 (1232.88 mg, 3.78 mmol) in l,4-Dioxane (15 mL) and Water (1.5 mL) was stirred at 60 C for 5 hours under N2. After cooling to room temperature, the mixture was concentrated to give the residue. The residue was diluted with FLO (20 mL), and the mixture was extracted with EtOAc (30 mL x 2). The combined organic phase was washed with water (20 mL) and brine (20 mL), dried over Na2S04,filtered and concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 3%) to give the product (350 mg, 1.15 mmol, 61% yield) as an oil. LCMS Rt= 0.95 min in 1.5 min chromatography, 5-95 AB, MS ESI calcd. for C i HioCIFiN iO [M+H]+304.0, found 304.1.

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

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; MARTINEZ BOTELLA, Gabriel; REDDY, Kiran; WITTMANN, Marion; (0 pag.)WO2019/232209; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 32587-10-3, name is 3-Aminopyrazine-2-carboxamide, belongs to pyrazines 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 32587-10-3, Recommanded Product: 32587-10-3

(c) In 9 mL of trifluoroacetic acid was dissolved 0.3 g of 3-amino-2-pyrazinecarboxamide. At an ice-cooled temperature, 10% fluorine gas (a fluorine gas diluted with nitrogen gas) was introduced into the solution at a rate of 45 ml per minute for a period of 22 minutes. After stirring the mixture at an ice-cooled temperature for 17 minutes, the temperature was elevated to room temperature. The reaction mixture was added to a mixture of 30 mL of saturated aqueous solution of sodium hydrogen carbonate and 30 mL of ethyl acetate, and the organic layer was separated. The remaining aqueous layer was acidified with 6 mol/L hydrochloric acid and then extracted with 20 ml of ethyl acetate. The organic layers thus obtained were united, washed successively with 10 mL of water and 10 mL of saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=2:1] to obtain 0.015 g of 3-amino-6-fluoro-2-pyrazinecarboxamide as a light yellow-colored solid product.

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-Aminopyrazine-2-carboxamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Toyama Chemical Co., Ltd.; US2003/130213; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem