Category: Pyrazines

Electric Literature of 98-97-5,Some common heterocyclic compound, 98-97-5, name is Pyrazine-2-carboxylic acid, molecular formula is C5H4N2O2, 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-carb aldehyde A round bottom flask was charged with pyrazine carboxylic acid (17.7 g, 140 mMol), methanol (200 mL) and conc. sulphuric acid (2 mL) and the mixture was stirred at reflux for 4 hrs then left to stand overnight. The next day the mixture was refluxed for 2 more hours. The solvent was then evaporated in vacuo, the residue was diluted with dichloromethane and neutralised with 20% sodium bicarbonate solution. The dichloromethane phase was dried over MgS04 and evaporated to give the crude product as an off-white solid. Purification by column chromatography (silica gel, dichloromethane) gave pyrazinecarboxylic acid methyl ester 13.5 g as a white solid.

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

Reference:
Patent; F2G LTD; WO2005/92304; (2005); A2;,
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.

To a solution containing 1.63 g (7.5 mmol) of 2-amino-5-bromopyrazine carboxylic acid in 25 mL of DMF was added 3.54 g (9.36 mmol) of HATU. The reaction mixture was allowed to stir for 15 minutes before the addition of 1.68 g (9.36 mmol) of 3-amino-4- morpholinopyridine and 2.5 mL (22.5 mmol) of N-methylmorpholine. The reaction was stirred for 16 h then quenched with a 10 mL of a saturated NaHCO, solution and extracted with EtOAc three times. The combined organic extracts were washed with brine and dried over Na2S04. Evaporation of the solvent and column chromatography (Si02; 10% CH3OH /DCM) provided Intermediate A as a yellow solid. 1H NMR (CD3OD) d 9.51 (s, 1H), 8.76 (s, 1H), 8.39 (d, J=5.4Hz, 1H), 7.94 (d, J=8. lHz, 2H), 7.39-7.27 (m, 8H), 5.10 (s, 2H), 3.81 (t, J=7.5Hz, 4H), 2.96 (t, J=7.5Hz, 4H). [M+H]+ = 568.1.

Statistics shows that 3-Amino-6-bromopyrazine-2-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 486424-37-7.

Reference:
Patent; SILVERBACK THERAPEUTICS, INC.; SMITH, Sean Wesley; COBURN, Craig Alan; BAUM, Peter Robert; DUBOSE, Robert Finley; (335 pag.)WO2019/227059; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 5049-61-6, 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. 5049-61-6, name is Pyrazin-2-amine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Initial attempt showed that the reaction gave a lot of black polymers after a few min., with the main product being 3,5-dichloro-2-amino pyrazine. Only small amount of 5- chloro-2-aminopyrazine was isolated (eq 7). This reaction could not be scaled up because it was not reproducible.

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, Pyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; THE GOVERNMENT OF THE UNITED STATES, as represented by the secretary of HEALTH AND HUMAN SERVICES; WO2007/124345; (2007); 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. 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, A new synthetic method of this compound is introduced below., Recommanded Product: (3,5,6-Trimethylpyrazin-2-yl)methanol

In a 50 ml round-bottom flask the compound TMP-OH (1.52 g 10 mmol) was added and dissolved in 20 mL of anhydrous ethanol active manganese dioxide (2.61 g 30 mmol) was added heated to reflux for 3 hours and monitored by TLC until the starting material completely comsumed and the resulting material was filtered and concentrated and separated with column chromatography eluted with ethyl acetate /petroleum ether (11) to give the compound TMP-CHO as a white solid (0.99 g 66) .

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; GUANGZHOU MAGPIE PHARMACEUTICAL CO., LTD; WANG, Yuqiang; YOUDIM, Moussa B.H.; SUN, Yewei; ZHANG, Zaizun; ZHANG, Gaoxiao; YU, Pei; YI, Peng; LIANG, Ming; LIU, Wei; WO2015/109935; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 16298-03-6,Some common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, molecular formula is C6H7N3O2, 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 mixture of methyl 3-aminopyrazine-2-carboxylate (6.30 g, 41.14 mmol, 1 eq.) andiV- o bromosuccinimide (7.322 g, 41.14 mmol, 1 eq.) in 100 mL acetonitrile was refiuxed for 2 h until there was no starting material left according to LC/MS. The solvent was removed in vacuo. To the residue was added isopropanol. After filtration, the crude product was collected as a solid. Additional product could be collected from the mother solution. Thus, 12.136 g of crude product was obtained (127 %). The crude product was used directly in 5 the next step without further purification.1H NMR (400 MHz, DMSO-cfc) delta (ppm) 3.85 (s, 3H)5 7.55 (br s, 2H), 8.42 (s, IH).

The synthetic route of 16298-03-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WO2007/61360; (2007); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 59489-71-3 as follows. Recommanded Product: 59489-71-3

In a sealed tube, sodium methoxide (25 wt. %, 10 mL) was added to a suspension of 5-bromopyrazin-2-amine (1.12 g, 6.44 mmol) in MeOH (10 mL). The reaction was stirred at 100C for 40 h. At 15 h reaction time, reaction is about 40 % complete by LCMS. At 40 h reaction time, reaction is about 90% complete. After concentration the residue was taken up in EtOAc and extracted with brine, dried over sodium sulfate, concentrated and purified by flash chromatography on a 120 g silica gel cartridge with 30 to 50% EtOAc in hexane, 45 min, at 35 mL/min. Pure fractions were pooled, concentrated and dried under high vac to give 5-methoxypyrazin-2-amine (455 mg, 57 %).1H NMR (400 MHz, CDCl3) d ppm 7.75 (1 H, d, J=1.26 Hz), 7.55 (1 H, d, J=1.51 Hz), 4.12 (2 H, br. s.), 3.87 (3 H, s). LCMS (method K) tR, 0.55min., MH+ = 126.1.

According to the analysis of related databases, 59489-71-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Iwuagwu, Christiana; King, Dalton; McDonald, Ivar M.; Cook, James; Zusi, F. Christopher; Hill, Matthew D.; Mate, Robert A.; Fang, Haiquan; Knox, Ronald; Gallagher, Lizbeth; Post-Munson Amy Easton, Debra; Miller, Regina; Benitex, Yulia; Siuciak, Judy; Lodge, Nicholas; Zaczek, Robert; Morgan, Daniel; Bristow, Linda; Macor, John E.; Olson, Richard E.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 5; (2017); p. 1261 – 1266;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 32111-28-7, A common heterocyclic compound, 32111-28-7, name is N-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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.

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.

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

Adding a certain compound to certain chemical reactions, such as: 313339-92-3, name is 3,5-Dichloropyrazine-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 313339-92-3, Quality Control of 3,5-Dichloropyrazine-2-carbonitrile

107281 3,5-Dichloropyrazine-2-carbonitrile (Example 12, Step 2, 31.0 g, 178.18 mmol) was dissolved in anhydrous diethyl ether (890 mL, 0.2 M) and cooled to -78 C. Then MeMgBr indiethyl ether (3.0 M, 65.3 mL, 190 mmol) was added slowly to maintain low temperature. After the addition was complete, the mixture was slowly warmed room temperature and stirred at room temperature for 1 h. The mixture was poured into a beaker containing a mixture of HC1 in water (1.0 M, 1 L) and ice (1 kg). The mixture was stirred vigorously for 10 mm. The mixture was extracted with diethyl ether (3 X 1 L). The combined organic layers were dried over Na2504 andconcentrated under reduced pressure to afford the title compound as an orange oil (34 g, 99% yield). The mixture was used for the next reaction without further purification. ?H NMR (400 IVIHz, CDC13): ppm 8.56 (s, 1H), 2.71 (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, 3,5-Dichloropyrazine-2-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FLX BIO, INC.; BECK, Hilary, Plake; BIANNIC, Berenger; BUI, Minna Hue, Thanh; HU, Dennis, X.; KETCHAM, John, Michael; POWERS, Jay, Patrick; REILLY, Maureen, Kay; ROBLES-RESENDIZ, Omar; SHUNATONA, Hunter, Paul; WALKER, James, Ross; WUSTROW, David, Juergen; YOUNAI, Ashkaan; ZIBINSKY, Mikhail; (396 pag.)WO2018/22992; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

16298-03-6, name is Methyl 2-aminopyrazine-3-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. Recommanded Product: 16298-03-6

(A) Methyl 2-bromo-3-pyrazine carboxylate To a stirred mixture of 12.7 g. of methyl 2-amino pyrazine carboxylate and 47 ml. of 48% hydrobromic acid there was added, dropwise, 12.6 ml. of bromine keeping the temperature at 0. A solution of 14.4 g. of sodium nitrite in 60 ml. of water was then added, dropwise, at 0 and the reaction mixture stirred for 15 minutes. The reaction mixture was basified to pH 8 with sodium bicarbonate and extracted with ethyl acetate and again with chloroform. The organic layers were dried over magnesium sulfate, filtered and concentrated to a yellow oil. Recrystallization from ether-hexane yielded the product, m.p. 43-45 C.

The synthetic route of 16298-03-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Schering Corporation; US4632923; (1986); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4774-14-5, 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 4774-14-5 as follows.

2,2,6,6-tetramethylpiperidine (2.84 g, 20.1 mmol) in THF (250 mL) at -100C was added n-butyllithium (13.8 mL, 22.1 mmol). The solution was stirred for 20 minutes and cooled to -90C. 2,6-Dichloropyrazine (3.0 g, 20.1 mmol) in THF (10 mL) was added to the solution followed by carbon dioxide (89 g, 2014 mmol) as dry ice powder. The mixture was then allowed to warm to room temperature while stirring. The reaction mixture was concentrated under reduced pressure, diluted with water (20OmL) and acidified with 10% aq. HCl solution to pH 2. Extraction with EtOAc (x3) was followed by extraction with saturated aq. NaHCO3 solution. The aquous solution was acidified carefully with 10% aq. HCl solution to pH 2. The solution was extracted with EtOAc(x3) and the resulting solution was washed with water and brine. The organics were dried over anhydrous MgSO4 and concentrated. The resulting solid was trituated with Hex/chloroform (1 :1) and the remaining solid was filtered and washed with hexane to provide the title compound as an off-white solid (1.78 g, 9.22 mmol, 45.8% yield); IH NMR (400 MHz, DMSO-J6) delta ppm 8.90 (s, 1 H).

According to the analysis of related databases, 4774-14-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SIGNAL PHARMACEUTICALS, LLC; WO2009/89042; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem