Pyrazines

13301-04-7, name is Methyl 3,6-dibromopyrazine-2-carboxylate, belongs to pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Product Details of 13301-04-7

To a solution of methyl 3,6-dibromopyrazine-2-carboxylate (8.4 g, 28.3 mmol) in MeCN (142 mL) was added (3Patent; REVOLUTION MEDICINES, INC.; LI, Jie Jack; KOLTUN, Elena S.; GILL, Adrian Liam; BUCKL, Andreas; WON, Walter; AAY, Naing; MELLEM, Kevin; TZITZILONIS, Christos; JOGALEKAR, Ashutosh; CREGG, James Joseph; (177 pag.)WO2019/75265; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1379338-74-5, The chemical industry reduces the impact on the environment during synthesis 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, I believe this compound will play a more active role in future production and life.

(A) methyl 3-(7-chloropyrido[4,3-ib]pyrazi n-5-ylamino)propanoate.[01 62] A solution of methyl 3-aminopropanoate hydrochloride (4.88 mmol), Et3N (6.50 mmol) and 5,7-dichloropyrido[4,3-£>]pyrazine (3.25 mmol) in THF (10 mL) was stirred at room temperature overnight. Volatiles were removed under reduced pressure, and the residue was treated with water and extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered, and concentrated. The residue was purified by chromatography to afford the title compound. MS (m/z): 267 (M+H)+.

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, 5,7-Dichloropyrido[3,4-b]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; HUTCHISON MEDIPHARMA LIMITED; SU, Wei-Guo; DENG, Wei; JI, Jianguo; WO2012/167423; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 889447-19-2,Some common heterocyclic compound, 889447-19-2, name is 2-Chloro-5H-pyrrolo[2,3-b]pyrazine, molecular formula is C6H4ClN3, 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 1M solution of iodine chloride in dichloromethane (4ml, 4mmol) was added dropwise to an ice-cold solution of 2-chloro-5H-pyrrolo[2,3-&]pyrazine (4) in N-methylpyrrolidone (residual from previous step) and pyridine (5ml). The reaction mixture was stirred for 60 minutes at O0C and then was concentrated in vacuo. The residue was purified by flash chromatography, using as eluent pentane/EtOAc 0% to 50%, to give the title compound (820 mg, 75% over two steps). 1Eta NMR (DMSO-d6) 8.2 (lEta,s), 8.4 (IH, s). MS(ES+): 280

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-5H-pyrrolo[2,3-b]pyrazine, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2006/58074; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 4858-85-9,Some common heterocyclic compound, 4858-85-9, name is 2,3-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.

A. Preparation of the intermediate compounds; A1. Preparation of intermediate compound 1; 2,3-Dichloropyrazine (10 g, 62.12 mmol) and 1-(phenylmethyl)-4-piperidinamine (13.73 mL, 67.12 mmol) were dissolved in DMF (60 ml). Then Na2CO3 (10.09 g, 1 14.10 mmol) was added. The reaction was stirred at 130 0C for 16 hours. The solid was filtered off, washed with AcOEt and the solvent was evaporated till dryness. The product was dissolved in AcOEt, washed with H2O and brine, dried with MgSO4 and evaporated under vacuum yielding 15 g of the desired intermediate compound 1 (74 %).The product was used without any 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 2,3-Dichloropyrazine, its application will become more common.

Reference:
Patent; JANSSEN PHARMACEUTICA N.V.; WO2007/122173; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 14667-55-1, name is 2,3,5-Trimethylpyrazine, A new synthetic method of this compound is introduced below., SDS of cas: 14667-55-1

Take 2,3,5-trimethylpyrazine (16.3 mL, 98.7 mmol) in a 500 mL round bottom flask, glacial acetic acid (60 mL) and 30% hydrogen peroxide (50 mL) were slowly added with a constant pressure funnel while stirring in an ice bath, the reaction solution was stirred and heated in an oil bath at 60 C, an equal amount of 30% hydrogen peroxide was added dropwise to the reaction solution, and the mixture was stirred for 20 hours, cooled to room temperature, water (50 mL) was added, rhoEta was adjusted = 9 with saturated K2C03, extracted with DCM (200mLX4), the organic phase was washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated to give 12.4 g of a pale yellow oily liquid, yield was 76%.

The synthetic route of 14667-55-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guizhou Medical University; Fan Lingling; Tang Lei; Li Yi; Li Yong; Liu Jian; Chu Liangzhao; (28 pag.)CN108558833; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 54608-52-5, 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 54608-52-5 as follows.

Step 1 2,2-difluoro-N’-pyrazin-2-yl-acetohydrazide difluoroacetate Pyrazin-2-yl-hydrazine 23a (1 g, 9 mmol) was added in an eggplant-shaped bottle (25 mL), followed by dropwise addition of difluoroacetic anhydride (4 g, 22.98 mmol) at 0 C. After stirring at room temperature for 3 hours, the reaction mixture was concentrated under reduced pressure to obtain crude 2,2-difluoro-N’-pyrazin-2-yl-acetohydrazide difluoroacetate 23b (2 g) as a brown oil. The product was used directly in the next reaction without purification.

According to the analysis of related databases, 54608-52-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JIANGSU HANSOH PHARMACEUTICAL CO., LTD.; Tang, Peng Cho; Li, Xin; Li, Xiangqin; Chen, Yang; Wang, Bin; Zhu, Zhe; US2013/131068; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, A new synthetic method of this compound is introduced below., Safety of 2-Bromo-5-chloropyrazine

A mixture of 2-bromo-5-chloro-pyrazine (2 g, 10.34 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-[(lR)-2,2,2-trifluoro-l- methyl-ethoxy]pyridine (3.12 g, 9.31 mmol), Pd(dppf)Cl2 (1.13 g, 1.55 mmol) and CS2CO3 (6.74 g, 20.68 mmol) in l,4-dioxane (100 mL) and water (10 mL) was stirred under N2 at 50 C for 5 hours. After cooling to room temperature, the mixture was diluted with EtOAc (10 mL), filtered with silica gel, eluted with EtOAc (20 mL) and concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 20%) to give the product (2500 mg, 7.21 mmol, 70% yield) as a solid. ‘H NMR (400MHz, CDCI3) dH= 8.77 (d, 1H), 8.64 (d, 1H), 8.53 (d, 1H), 8.08 (dd, 1H), 6.00 – 5.83 (m, 1H), 1.59 (d, 3H).

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; 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

These common heterocyclic compound, 87486-33-7, name is 3,5-Dichloro-1-methylpyrazin-2(1H)-one, 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. COA of Formula: C5H4Cl2N2O

A solution containing 3,5-dichloro-l-methylpyrazin-2(lH)-one (300 mg, 1.676 mmol) (CAS 87486-33-7), tetramethyltin (0.256 mL, 1.844 mmol) and tetrakis(triphenylphosphine)palladium(0) (48.4 mg, 0.042 mmol) in DMF (2 mL) in a Biotage microwave vial was sealed with a Teflon-lined septa cap. The vial was evacuated under vacuum and backfilled with nitrogen gas, using a needle from a vacuum manifold. The procedure repeated and the nitrogen line removed. The vial was heated in a Biotage microwave at 150 C for 20 min. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (50 mL) and washed with aqueous 10% NaF solution (2×10 mL) and saturated aqueous NaCl solution (1×10 mL), dried (Na2S04), filtered and concentrated. The crude product was dissolved in a small amount of DCM and charged to a 10 g ISCO silica gel column, placed on a Teledyne ISCO system and eluted over a 20 min gradient using 0%-100% hexanes/ethyl acetate eluent to afford 5- chloro-l,3-dimethylpyrazin-2(lH)-one (170 mg, 1.072 mmol, 64.0 % yield). LCMS MH+: 159.0. HPLC Ret. Time 0.52 min. Method Bl. NMR (400 MHz, CHLOROFORM-d) delta 7.13 (bm, 1H), 3.52 (s, 3H), 2.48 (d, J=0.6 Hz, 3H). Fragment 21 : 6-Chloro-2,4,5-trimethylpyridazin-3(2H)-one

The synthetic route of 3,5-Dichloro-1-methylpyrazin-2(1H)-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; DYCKMAN, Alaric J.; DODD, Dharmpal S.; HAQUE, Tasir Shamsul; WHITELEY, Brian K.; GILMORE, John L.; (192 pag.)WO2019/28302; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 36070-79-8, 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. 36070-79-8, name is 6-Chloropyrazine-2-carboxamide belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: 150 mg (0.952 mmol) of 5-Cl-PZA (1) or 6-Cl-PZA (2) was dissolved in ethanol together with triethylamine (1 eq., 96 mg, 0.952 mmol). Three equivalents of corresponding alkylamine were added to the reaction mixture and refluxed in ethanol generally for 6 hours. The completion of the reaction was checked by TLC chromatography (eluent: hexane/ethyl acetate, 1:2). The crude product was absorbed on silica by solvent evaporation and purified by flash chromatography (hexane/ethyl acetate gradient elution).

The synthetic route of 6-Chloropyrazine-2-carboxamide has been constantly updated, and we look forward to future research findings.

Reference:
Article; Servusova, Barbora; Paterova, Pavla; Mandikova, Jana; Kubicek, Vladimir; Kucera, Radim; Kunes, Jiri; Dolezal, Martin; Zitko, Jan; Bioorganic and Medicinal Chemistry Letters; vol. 24; 2; (2014); p. 450 – 453;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, 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 939412-86-9, name: (3-Chloropyrazin-2-yl)methanamine hydrochloride

Into a round bottom 1-neck flask (5L), 3-oxo-cyclobutanecarboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester (217.2 g, 0.937 mol), C-(3-chloro-pyrazin-2-yl)-methylamine hydrochloride salt (153.3 g, 0.852 mol), and THF (760 mL) were added. A solution of 10% NaHCO3 (1.07 kg) was then added and after 20 min, the layers were allowed to separate and the aqueous layer was removed. The aqueous layer was back extracted with EtOAc (1×700 mL, 1×300 mL). The combined organics were washed with brine (350 mL), dried over MgSO4, filtered, and concentrated in vacuo to provide the title compound. This solid was resuspended in ethyl acetate (915 mL) and DMF (132 mL) and the solution was put under an atmosphere of nitrogen and cooled to 10.5 C. Phosphorus oxychloride (159 mL, 1.70 mol) was then added over 15 minutes and the reaction was allowed to stir for 45 min. The reaction solution was then poured slowly into a 22% aqueous Na2CO3 solution at 10IC. Water (1 L) was added and the layers were allowed to separate. The organic layer was removed and the aqueous was back extracted with EtOAc (1×1 L, 1×0.5 L). The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo until about 0.5 L of solvent remained. Heptane was added and the slurry was concentrated in vacuo until most of the EtOAc was removed. The resultant slurry was filtered to give desired product. 1H NMR (400 MHz, CDCl3) delta 3.59-3.68 (m, 2H), 3.72-3.79 (m, 2H), 3.86-3.94 (m, 1H), 7.40 (d, 1H, J=5.2 Hz), 7.60 (d, 1H, J=5.2 Hz) and 7.85 (s, 1H).

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; Buck, Elizabeth A.; Griffin, Graeme; Barr, Sharon M.; US2007/280928; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem