Category: Pyrazines

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 61892-95-3 as follows. COA of Formula: C6H8N2O

To a solution of (5-methylpyrazin-2-yl)methanol (500 mg, 4.028 mmol, commercial source: Combi- Blocks) in dichloromethane (20 mL), thionyl chloride (0.35 mL, 4.825 mmol, Commercial source: Avra) was added slowly at 0 C. The reaction mixture was allowed to reach 26 C and stirred for 16 h at the same temperature. Upon completion, the reaction mixture was concentrated under reduced pressure. The residue was neutralized with saturated sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic solution was dried over Na2S04, filtered and the filtrate was concentrated under reduced pressure to afford 2- (chloromethyl)-5-methylpyrazine (500 mg, crude) as a brown liquid.1H NMR (400 MHz, CDCI3) delta 8.60 (s, 1 H), 8.43 (s, 1 H), 4.67 (s, 2H), 2.59 (s, 3H). MS m/z [M+H]+= 143.04

According to the analysis of related databases, 61892-95-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ALEMPARTE-GALLARDO, Carlos; ENCINAS, Lourdes; ESQUIVIAS PROVENCIO, Jorge; (206 pag.)WO2019/34729; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5049-61-6,Some common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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 solution of 2-aminopyrazine (1.0 g, 10.5 mmol) in dioxane (25 mL) was added ethyl 3-bromo-2-ketopropionate (2.0 g, 10.5 mmol). The reaction was stirred at 50 C for 16 h. The mixture was filtered and the solid was washed with two portions of ethyl acetate. The solid was heated in 35 ML of isopropanol at reflux temperature for 4 h. The reaction mixture was concentrated and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous phase was extracted with three portions of ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate, and concentrated. Purification by chromatography (Biotage system, silica gel, ethyl acetate then 10% methanol/ethyl acetate) gave the title compound as a solid.

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

Reference:
Patent; MERCK & CO., INC.; WO2004/58266; (2004); 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. 56423-63-3, name is 2-Bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 56423-63-3

General procedure: In a conical flask (50mL), a mixture of aryl halide (1 mmol), phenyl boronic acid (1.2 mmol),triethylamine (1 mmol), [Aemim]Br (1ml) and [Gmim]Cl-Pd (II) (0.1mol%, 5 mg)was added and stirred at 25OC for a period as indicated in Table 5(The reaction was monitored by HPLC and TLC). The resulting heterogeneousmixture was extracted with ethyl acetate or diethyl ether (3x 5 mL). Theorganic phase was separated and dried over anhydrous Na2SO4and evaporated. Evaporation of the solvent gave the crud product residue whichwas further purified by flash chromatography using n-hexane/EtOAc to give thedesired coupling product in 82-94% isolated yields.

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 56423-63-3.

Reference:
Article; Karthikeyan, Parasuraman; Vanitha, Arumugam; Radhika, Pachaiappan; Suresh, Kannan; Sugumaran, Arunachalam; Tetrahedron Letters; vol. 54; 52; (2013); p. 7193 – 7197;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4745-93-1, name is 5H-Pyrrolo[2,3-b]pyrazine, 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. Application In Synthesis of 5H-Pyrrolo[2,3-b]pyrazine

Step 8-Preparation of propane-1-sulfonic acid {2-fluoro-3-[hydroxy-(5H-pyrrolo[2,3-b]pyrazin-7-yl)-methyl]-phenyl}-amide (19); To propane-1-sulfonic acid (2-fluoro-3-formyl-phenyl)-amide (18, 50 mg, 0.42 mmol) in 0.8 mL of methanol, 5H-pyrrolo[2,3-b]pyrazine (3, 103 mg, 0.42 mmol) and potassium hydroxide (71 mg, 1.3 mmol) were added under an atmosphere of nitrogen. The reaction was stirred at room temperature for 48 hours, then poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 60% ethyl acetate in dichloromethane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a solid (19, 74 mg, 49%). MS (ESI) [M-H+]-=363.5.

The synthetic route of 4745-93-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ibrahim, Prabha N.; Spevak, Wayne; Cho, Hanna; US2009/306087; (2009); 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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine

General procedure: A mixture of chloro compound (50 mg) and amine derivative (2 equiv.) in PEG 400 (2 mL) wasstirred at 120 C for 5 min. After completion the reaction was then cooled to room temperature. DCM and water were added and the phases were separated. The aqueous phase was extracted withDCM and the organic phase was dried and filtered. The removal of solvent gave the product as solid.

According to the analysis of related databases, 68774-77-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Campos, Joana F.; Loubidi, Mohammed; Scherrmann, Marie-Christine; Berteina-Raboin, Sabine; Molecules; vol. 23; 3; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 19745-07-4, name is 2,5-Dichloropyrazine, 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 19745-07-4, Safety of 2,5-Dichloropyrazine

Intermediate C-5 2-chloro-3-((5-chloropyrazin-2-yl)thio)aniline A mixture of 3-amino-2-chlorobenzenethiol (724 mg, 3.69 mmol), 2,5- dichloropyrazine (500 mg, 3.36 mmol), and potassium carbonate (1.39 g, 10.07 mmol) in DMF/MeCN (1/1, 20 mL) was stirred for 4 h at 85 °C. After cooling to RT, the reaction mixture was filtrered through a pad of Celite followed by MeCN (10 mL) wash. The combined filtrates were concentrated under reduced pressure and the resulting residue was purified by silica chromatography (0 to 20percent gradient of EtO Ac/heptane) to give 2-chloro-3-((5-chloropyrazin-2- yl)thio)aniline (285 mg, 1.037 mmol). MS m/z. 272.1 (M+H)+.

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

Reference:
Patent; NOVARTIS AG; CHEN, Zhuoliang; FORTANET, Jorge Farcia; JOUK, Andriana; KARKI, Rajesh; LAMARCHE, Matthew J.; LIU, Gang; PALERMO, Mark G.; PEREZ, Lawrence Blas; SARVER, Patrick James; SHULTZ, Michael David; SENDZIK, Martin; TOURE, Bakary-Barry; YU, Bing; (173 pag.)WO2016/203406; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

98-97-5, name is Pyrazine-2-carboxylic acid, 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. Formula: C5H4N2O2

Step A. Preparation o f Pyrazine-2-carbonyl chloride. A 500 ml three neck round bottomed flask equipped with a stir bar, thermocouple, heating mantle with digital temperature controller, condenser and nitrogen inlet/outlet was charged with 15 g (0.12 mol) of pyrazine carboxylic acid, 225 mL of toluene (Kf < 0.02wt%) and 26.4 ml (43 g, 0.36 mol) of thionyl chloride. The thin slurry was heated to 75 C and stirred overnight (10-16 hr). After cooling the reaction mixture to room temperature the solvent and excess thionyl chloride were removed in vacuo as follows: Reaction mixture was stripped under full vacuum at 60 C (bath temperature) to approximately 1/3 its original volume and then (175 ml) of fresh toluene was added. Concentration was continued, again stripping to 1/3 original volume followed by re-dilution with 225 ml of fresh toluene to provide the pyrazine acid chloride in a toluene solution. The synthetic route of 98-97-5 has been constantly updated, and we look forward to future research findings. Reference:
Patent; CEPHALON, INC.; ROEMMELE, Renee Caroline; WO2011/87822; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486424-37-7, These common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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.

METHOD 11; Example 305; Synthesis of tert-butyl l-(3-(3-amino-6-bromopyrazine- 2-carboxamido)pyridin-4-yl)prperidin-3-ylcarbamate [0242] A solution containing 1 eq each of tert-butyl l-(3-aminopyridin-4- yl)piperidin-3-ylcarbamate, S-amino-beta-bromopyrazine-l-carboxylic acid, HOAT and EDC in DMF, at a concentration of 0.5 M, was stirred for 60 hours. The solution was diluted with EtOAc and was washed with H2O (4x), NaCl(sat.), was dried over MgSO4, was filtered and the volatiles were removed in vacuo. After purification by silica gel chromatography (EtOAc eluant), tert-butyl l-(3-(3-amino-6-bromopyrazine-2- carboxamido)pyridin-4-yl)piperidin-3-ylcarbamate was obtained (78%). LCMS (m/z): 492.2 (MH+); LC R, = 2.68 min.

The synthetic route of 486424-37-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS VACCINES AND DIAGNOSTICS, INC.; WO2008/106692; (2008); 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. 951626-95-2, name is Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., name: Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

[00593] A 60 % dispersion of sodium hydride in mineral oil (0.395 g, 9.88 mmol) was added to a stirred solution of ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[l,5-a]pyrazine-2- carboxylate (1.88 g, 8.98 mmol) in DMF at 0 C. The mixture was stirred at this temperature for 1 h. Then, benzyl bromide was added and the mixture was stirred at room temperature for further 3 h. The mixture was diluted with water and extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo to yield ethyl 5 oenzyl- 4-oxo-4,5,6,7-tetrahydropyrazolo[l,5-a]pyrazine-2-carboxylate as a white oil (1.87 g, 66 % yield).

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; VANDERBILT UNIVERSITY; CONN, P., Jeffrey; LINDSLEY, Craig, W.; STAUFFER, Shaun, R.; BARTOLOME-NEBREDA, Jose Manuel; CONDE-CEIDE, Susana; MACDONALD, Gregor, James; TONG, Han Min; ALCAZAR-VACA, Manuel Jesus; ANDRES-GIL, Jose Ignacio; WO2013/192350; (2013); 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. 27398-39-6, name is 3-Chloropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Formula: C5H3ClN2O2

To a suspension of sodium hydride (278 mg, 6.95 mmol, 60percent in oil) in DMF (10 mL) was added 1H-pyrazole (279 mg, 4.11 mmol) at RT and the resulting mixture was stirred at room temperature for 30 mins. 3-Chloropyrazine-2-carboxylic acid (500 mg, 3.16 mmol) wasadded and the mixture heated to 60 °C for 2 h. After cooled to RT, water (20 mL) was added and the mixture extracted with 4.7percent MeOH in DCM (20 mL x 3). The combined organic layers were washed with brine, dried over Na2504, filtered, and concentrated in vacuo to give the title compound. LRMS m/z (M+H) 191.0 found, 191.0 required.

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 27398-39-6.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KIM, Ronald; KUDUK, Scott, D.; LIVERTON, Nigel; ZHUO, Gang; (97 pag.)WO2016/100157; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem