Pyrazines

Electric Literature of 6705-33-5,Some common heterocyclic compound, 6705-33-5, name is Pyrazin-2-ylmethanol, molecular formula is C5H6N2O, 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.

Powdered potassium hydroxide (3.4 g, 60 mmol) was added to a mixture of 2-chloro- L-FLUORO-4-NITROBENZENE (10.5 g, 60 mmol) AND PYRAZIN-2-YLMETHANOL (6.6 g, 60 mmol ; Maury G. et al. , Bull. Soc. Chem. Belg. 1982,91, 153). Tetrabutylammonium bromide (50 mg) was added and the mixture was heated AT 80C for one hour and cooled to room temperature. The residue was dissolved in dichloromethane, washed with water and dried over magnesium sulfate. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 5% ethyl acetate in dichloromethane) to give 2- [ (2-CHLORO-4- nitrophenyl) oxymethyl] pyrazine (6.4 g, 40%) as a yellow solid. NMR Spectrum: (CDC13) 5.41 (s, 2H), 7.14 (d, 1H), 8.18 (dd, 1H), 8. 35 (d, 1H), 8.61 (d, 2H), 8.94 (s, 1H).

The synthetic route of 6705-33-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/26151; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 74290-69-0, 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. 74290-69-0 name is 5-Bromo-6-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.

Step 6: methyl 5-amino-3-methylpyrazine-2-carboxylate A 5 L pressure tank reactor was charged with 5-bromo-6-methylpyrazin-2-amine (510 g, 2.71 mol, 1.00 equiv), triethylamine (830 g, 8.22 mol, 3.02 equiv), methanol (3.5 L) and Pd(dppf)Cl2 (60 g). The reactor was pressurized with CO gas (10 atm) and was stirred for 24 h at 70 C. The pressure was then released; and the resulting solid was filtered off. The filtrate was concentrated under vacuum. Water was added to the resulting residue and the mixture was extracted with ethyl acetate (6 x 1 L). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give the title compound, which was used in the next step without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromo-6-methylpyrazin-2-amine, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; COLLETTI, Steven, L.; DEMONG, Duane; DYKSTRA, Kevin, D.; HU, Zhiyong; MILLER, Michael; (104 pag.)WO2019/99315; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-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. HPLC of Formula: C6H7ClN4O2

To a suspension of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester (10.0 g, 49.35 mmol) in methanol (5 mL) was added lithium hydroxide solution (4.17 g, 98.7 mmol in 40 mL water) at room temperature. The reaction was heated to 50 °C and stirred for 2-3 h. The temperature was lowered to room temperature and the reaction stirred overnight. The resulting precipitate was collected by filtration and dried under vacuum to yield 5 (11.3 g, 97percent). Mass (m/z): 187 [M-Li].

The synthetic route of 1458-01-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE CALIFORNIA INSTITUTE FOR BIOMEDICAL RESEARCH; SCHULTZ, Peter G.; CHATTERJEE, Arnab K.; KUMAR, Manoj; WELZEL, Gustav; WO2015/3083; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 41110-34-3, 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. 41110-34-3, name is Ethyl 5-methylpyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 5-methyl-2-pyrazinecarboxylic acid ethyl ester (2) (0.01 mol) and hydrazine hydrate (0.02mol) in ethyl alcohol (20 mL) was refluxed for 3 h with consistent stirring. After realization of the reaction (examined by the TLC), the reaction mixture is cooled to room temperature and filtered. The crude product was recrystallized from ethanol to offer pure 5-methyl-2-pyrazine carboxylic acid hydrazide (3).

The synthetic route of Ethyl 5-methylpyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Article; Maddireddi, Chandra Sekhara Reddi; Parimi, Uma Devi; Reddy, Sreenivasa Reddy Bhimi; Mandapati, Satyanarayana Reddy; Asian Journal of Chemistry; vol. 28; 11; (2016); p. 2453 – 2456;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 41110-33-2, 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. 41110-33-2, name is Methyl 5-methylpyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To the starting material methyl 5-methylpyrazine-2-carboxylate (500 mg 3.3 mmol), THF was added and this was cooled to -78 C, followed by the addition of a 1.0 M methylenechloride solution of DIBAL-H (590 mg 3.6 mmol) and the mixture was stirred for 6 h at-78 C. TLC revealed very little starting material (>5%). The reaction mixture wasremoved from the dry ice bath and was quenched as per Fieser workup. Then 0.14 mLof water was slowly added followed by the addition of ethyl acetate 15 mL, add 0.14 mL15% aqueous sodium hydroxide. Then 0.36 mL water was added, warmed to rt and stirredfor 15 min after addition of Na2SO4 (250 mg). The reaction mixture was filtered over Hyflobed and the bed was washed thoroughly with EtOAc (50 mL). The organic layer wasevaporated under reduced pressure to dryness and purified using silica-gel flashchromatography. The pure product was characterized by NMR. Yield: 78%

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 5-methylpyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Balasubramaniam, Sivaraman; Vijayan, Sajith; Goldman, Liam V.; May, Xavier A.; Dodson, Kyra; Adhikari, Sweta; Rivas, Fatima; Watkins, Davita L.; Stoddard, Shana V.; Beilstein Journal of Organic Chemistry; vol. 16; (2020); p. 628 – 637;,
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. 6164-79-0, name is Methyl 2-pyrazinecarboxylate, A new synthetic method of this compound is introduced below., name: Methyl 2-pyrazinecarboxylate

To a stirred solution of sodium methoxide (25% in MeOH, 27.54 mL, 72.4 mmol, 1 eq) in 90 mL of toluene at 110 C. in a 3-neck flask attached with a mechanical stirrer, condenser and dropping funnel was added a solution of methylpyrazine-2-carboxylate (10 g, 72.4 mmol, 1 eq) in 115 mL of methyl acetate, dropwise, over a period of ?35-40 min. A yellow precipitate was formed. Stirring was continued at 110 C. for 3 hrs. The reaction was cooled and the yellow precipitate was filtered and washed with a small quantity of toluene. This solid was taken into 200 mL of saturated ammonium chloride and 400 mL of EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give 6.52 g (50%) of methyl 3-oxo-3-(pyrazin-2-yl)propanoate as a yellow solid.

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; Hoffmann-La Roche Inc.; Alam, Muzaffar; Bhagirath, Niala; Du Bois, Daisy Joe; Hawley, Ronald Charles; Minatti, Ana Elena; Kennedy-Smith, Joshua; Wilhelm, Robert Stephen; US2013/158040; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, 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 113305-94-5, category: Pyrazines

2- (2-Amino-4-methyl- phenoxymethyl) -morpholine-4-carboxylic acid tert-butyl ester (0.087 g, 0.270 mmol) was prepared from 2-amino-4- methyl-phenol according to methods of Compound 3, Steps 1 EPO and 2 using 2-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (prepared according to the procedure for Compound 2, Step 1 using the corresponding acid) and 4- methyl-2-nitro-phenol. It was combined with tr+/-phosgene (0.029 g, 0.10 mmol) , toluene (2 mL) and Hunig’s base(0.15 mL, 0.86 mmol), and stirred at room temperature for 25 min. The suspension then was transferred through a cannula to a cold solution (-780C) containing 5-amino- pyrazine-2-carbonitrile (0.032 g, 0.27 mmol), and lithium bis (trimethylsilyl) amide (0.27 mmol) in THF (1 mL) , which had been stirring at -78C for 30 min. The reaction was allowed to warm, then was stirred for 16 h at room temperature. A precipitate formed and was collected by- filtration to yield the desired product (0.043 cj).

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

Reference:
Patent; ICOS CORPORATION; WO2006/105262; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 123-32-0, name is 2,5-Dimethylpyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 2,5-Dimethylpyrazine

(b) 3,6-Dimethylpyrazin-2-amine[00426] A mixture of 2,5-dimethylpyrazine (14 g, 0.13 mol) in N,N-dimethylaniline (50 mL) was heated to 170 C and NaNH2 (22 g, 0.56 mol) was added in portions. The reaction mixture was stirred at 170 C for 1 h, and the solvent was removed. The product was purified by column chromatography to give 3,6-dimethylpyrazin-2-amine as a brown solid (1.6 g). MS (ESI): m/z 124[M+H]+.

The synthetic route of 123-32-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUNOVION PHARMACEUTICALS INC.; CAMPBELL, John, Emerson; HEWITT, Michael, Charles; JONES, Philip; XIE, Linghong; WO2011/150156; (2011); A2;,
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. 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, A new synthetic method of this compound is introduced below., name: 2-Bromo-5-(trifluoromethyl)pyrazine

Step 25 A: 2-[(3R.5R)-3.5-dimethylpiperazin-l -yll-5-(trifluoromethyl)pyrazine (0923) To a solid mixture of (2R,6R)-2,6-dimethylpiperazine dihydrochloride (0924) (0.08 g, 0.44 mmol, 1.0 eq), sodium fert-butoxide (0.21 g, 2.2 mmol, 5.0 eq) and bis(tri- ter/-butylphosphine)palladium(0) (34 mg, 0.07 mmol, 0.15 eq) was added dioxane (4 mL) followed by 2-bromo-5-(trifluoromethyl)pyrazine (0.10 g, 0.44 mmol, 1.0 eq) and the reaction mixture stirred at 50C overnight. The resulting suspension was filtered thru a pad of celite using EtOAc and concentrated. Silica gel column (24 g) was loaded using methylene chloride and run using an increasing gradient of MeOH (0-20%) in methylene chloride over 25 min. Following concentration of the product eluents, 2- [(3R,5R)-3,5-dimethylpiperazin-l-yl]-5-(trifluoromethyl)pyrazine 25a (0.09 g, 0.33 mmol, 75%) was isolated as a yellow oil.

The synthetic route of 1196152-38-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; HARRIOTT, Nicole; PAGANO, Nicholas; (135 pag.)WO2017/79641; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 274-79-3, These common heterocyclic compound, 274-79-3, name is Imidazo[1,2-a]pyrazine, 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.

The imidazo[1,2-a]pyrazine (7.2 g, 60.44 mmole) was dissolved in 2-methoxyethanol (100 ml) and PtO2 (1.2 g, 5.13 mmole) was added. The reaction mixture was stirred overnight at RT in an autoclave under a hydrogen atmosphere (4 bar). The autoclave was then flushed with nitrogen, the reaction mixture was filtered through filter earth, concentrated, and the solvent residues were then extracted with toluene. Purification was carried out by column chromatography on silica gel (DCM/7 N NH3 in methanol, 95:5)

Statistics shows that Imidazo[1,2-a]pyrazine is playing an increasingly important role. we look forward to future research findings about 274-79-3.

Reference:
Patent; GRUENENTHAL GmbH; US2009/186899; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem