Category: Pyrazines

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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Formula: C6H7N3O2

In fitted with magnetic stirring and reflux condensation tube (with drying tail pipe) 250 ml three-necked bottle are respectively added with a 3 – amino pyrazine -2 – carboxylic acid methyl ester 15.4g (about 0.1 muM), 120 ml of concentrated ammonia water, stirring at room temperature under the condition of 10h, filtering, washing, 60 C drying, be 12.5g yellow solid that 3 – amino pyrazine -2 – formamide. Yield: 90.6

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

Reference:
Patent; Li Zhulai; (15 pag.)CN106699759; (2017); A;,
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 13134-38-8 as follows. Computed Properties of C6H9N3

b. 2-(Chloromethyl)-5,8-dimethylimidazo[1,2-a]pyrazine To a solution of 3,6-dimethylpyrazin-2-amine (1.0 g, 8.1 mmol) in EtOH (20 mL) was added 1,3-dichloropropan-2-one (1.03 g, 8.1 mmol). The reaction mixture was stirred at reflux for 1 h. Then the solvent was removed. The product was purified by reverse column chromatography to give the title compound as a brown solid (570 mg, yield 85%). ESI MS: m/z 196 [M+H]+. 1H NMR (400 MHz, DMSO-d5): delta 8.10 (s, 1H), 7.65 (s, 1H), 4.94 (s, 2H), 2.70 (s, 3H), 2.54 (s, 3H).

According to the analysis of related databases, 13134-38-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sunovion Pharmaceuticals Inc.; US2012/178748; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 946493-27-2, These common heterocyclic compound, 946493-27-2, name is 3,5-Dimethylpyrazine-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.

[0443] To a 4 mL scintillation vial equipped with a stir bar was charged 3,5-dimethylpyrazine- 2-carboxylic acid (23.4 mg, 0.167 mmol), DMF (0.5 mL), HATU (66.4 mg, 0.174 mmol) and DIPEA (0.08 mL, 0,455 mmol). The mixture was stirred for 5 minutes at ambient temperature and then a solution of 3-amino-4-(4-(2,4-difluorophenoxy)piperidin-l -yl)benzonitrile (50 rng, 0.152 mmol) in DMF (0.5 mL) was added in a single portion. The reaction mixture was stirred at 70C overnight, then cooled to ambient temperature, and diluted with water (2 mL). The mixture was sonicated and stirred until a residue was observed around the inside of the vessel. The liquids were decanted, leaving an oily residue to which was added MeOH (~1 mL). The mixture was heated until it became a translucent solution and was then sonicated and stirred at ambient temperature until a precipitate was observed. The material was filtered and the solids were washed with minimal MeOH, collected, and dried under vacuum to give the title compound as a white solid (25.7 mg, 37%). NMR (400 MHz, DMSO-ifc) delta ppm 1.88 – 2.02 (m, 2 H), 2.10 – 2.24 (m, 2 H), 2.59 (s, 3 H), 2.85 – 3.00 (m, 5 H), 3.10 – 3.22 (m, 2 H), 4,47 – 4.64(m, 1H), 6.97 – 7.09 (m, i H), 7,27 – 7,45 (m, 3 H), 7.60 (dd, J=8.34, 2.02 Hz, 1H), 8.55 (s. 1H), 8.70 (d,./ 1.77 Hz, 1H), 10.71 (s, 1H); ESI-MS m/z [M i l . 464.2,

The synthetic route of 946493-27-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; GREEN, Jason; HOPKINS, Maria; JONES, Benjamin; KIRYANOV, Andre A.; KUEHLER, Jon; MONENSCHEIN, Holger; MURPHY, Sean; NIXEY, Thomas; SUN, Huikai; (300 pag.)WO2018/183145; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 33332-25-1, A common heterocyclic compound, 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, molecular formula is C6H5ClN2O2, 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.

Example 30 2- (3-CHLORO-4-METHANESULFONYL-PHENYL)-3-CYCLOPENTYL-N-(5-METHYLSULFANYLMETHYL- PYRAZIN-2-YL)-PROPIONAMIDE [000205] A solution of methyl 5-chloropyrazine-2-carboxylate (5.00 g, 28.97 mmol) in acetonitrile (290 ML) was treated with a fresh bottle of silver (I) fluoride (11.00 g, 86.70 mmol). The reaction setup was covered with aluminum foil, and the reaction mixture was heated at reflux overnight. The mixture was filtered through a pad of celite, and the pad of celite was rinsed with acetonitrile. The filtrate was then concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 25% ethyl acetate/hexanes) afforded 5-fluoro-pyrazine-2-carboxylic acid methyl ester (2.98 g, 66%) an off-white solid upon cooling to 0C. An analytical sample was obtained by trituration with petroleum ether to afford 5-fluoro-pyrazine-2-carboxylic acid methyl ester as a white crystalline solid: mp 55.6-56. 7C, EI-HRMS m/e calcd for C6HSFN202 (M 156.0335, found 156.0331.

The synthetic route of 33332-25-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2004/52869; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 50866-30-3, name is 5-Methylpyrazine-2-carbaldehyde, molecular formula is C6H6N2O, 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. HPLC of Formula: C6H6N2O

To a solution of N,N- bis(4-methoxybenzyl)ethanesulfonamide (Example 12.0, 73.13 g, 0.209 mol, 1.2 equiv.) in anhydrous THF (600 mL) at -78 C was added n-butyl lithium (83.71 mL, 0.209 mol, 2.5 M solution in hexanes, 1.2 equiv.) via additional funnel slowly, and the resulting mixture was stirred for 10 min. A solution of 5-methylpyrazine-2-carbaldehyde (Example 33.1, 21.3 g, 0.174 mol, 1.0 equiv.) in anhydrous THF (150 mL) was then added, and the resulting mixture was stirred at the same temperature for 45 min and allowed to warm to RT for 2 h. The reaction mixture was quenched by addition of an aqueous ammonium chloride solution (200 mL) and extracted with EtOAc (2 x 2 L). The combined organic layers were washed with brine (2 x 500 mL). After drying over anhydrous Na2SO4, the filtrate was concentrated in vacuo, to afford an oil. The oil thus obtained was purified by flash column chromatography (silica gel, 230-400 mesh) to afford the two isomers. The faster moving isomer (32 g as white solid) was obtained from the column with a gradient of 10 % to 30 % EtOAc in petroleum ether. 1H NMR (400 MHz, DMSO-d6) delta 8.61 (d, J = 1.5 Hz, 1H), 8.51 (d, J = 1.5 Hz, 1H), 7.22- 7.11 (m, 4H), 6.90- 6.80 (m, 4H), 6.10 (d, J = 5.9 Hz, 1H), 5.29 (dd, J = 5.9, 2.2 Hz, 1H), 4.36- 4.16 (m, 4H), 3.73 (m, 6H), 3.70-3.66 (m, 1H) 2.50 (merged with solvent peak, 3H) and 1.10 (d, J = 7.0 Hz, 3H). LCMS-ESI (pos.) m/z: 472.4 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 50866-30-3, its application will become more common.

Reference:
Patent; AMGEN INC.; CHEN, Yinhong; CHENG, Alan C.; DEBENEDETTO, Mikkel V.; DRANSFIELD, Paul John; HARVEY, James S.; HOUZE, Jonathan; KHAKOO, Aarif Yusuf; LAI, Su-Jen; MA, Zhihua; PATTAROPONG, Vatee; SWAMINATH, Gayathri; KREIMAN, Charles; MOEBIUS, David C.; SHARMA, Ankit; (543 pag.)WO2018/93580; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 19745-07-4, name is 2,5-Dichloropyrazine, 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. Computed Properties of C4H2Cl2N2

A solution of 2,5-dichloropyrazine (1.03 g, 6.91 mmol) in DMSO (10 mL) was treated sequentially with K2C03(s) (2.867 g, 20.74 mmol) and tert-butyl piperazine-1-carboxylate (1.288 g, 6.9 14 mmol), then stirred overnight at 75 ¡ãC. After cooling to ambient temperature, the mixture was partitioned between EtOAc (10 mL) and water (20 mL). After phase separation, the organic extracts were concentrated in vacuo to provide the title compound (1.928 g, 93percent yield). MS (apci) m/z = 199.1 (M-Boc). ?HNIVIR(CDC13) 8.07 (m, 1H), 7.86 (m, 1H), 3.56 (s, 8H), 1.48 (s, 9H).

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

Reference:
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; TANG, Tony P.; REN, Li; (668 pag.)WO2018/71447; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 723286-68-8, These common heterocyclic compound, 723286-68-8, name is Ethyl 5,6,7,8-Tetrahydro-1,2,4-triazolo[4,3-a]pyrazine-3-carboxylate, 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 title compound was prepared following general procedure B from Intermediate-1A, except ethyl 5,6,7,8-tetrahydro-[l,2,4]triazolo[4,3-a]pyrazine-3-carboxylate (4 equiv.) was the amine reactant, and the reaction was run in THF. The workup was carried out in dichloromethane and brine. The crude material was purified via silica gel chromatography utilizing a 0-10% methanol/dichloromethane gradient to deliver the desired Intermediate-9 (42 mg, 37% yield) as a solid. ‘H-NMR (400 MHz, CDC13) delta 8.47 (d, IH), 8.35 (d, IH), 7.40 (s, IH), 7.21 -7.16 (m, IH), 7.01 (t, IH), 6.95 (t, IH), 6.84 (t, IH), 6.65 (d, IH), 5.98 (s, 2H), 5.35 (s, 2H), 4.59 (t, 2H), 4.48 (q, 2H), 4.30 (t, 2H), 1.44 (t, 3H).

Statistics shows that Ethyl 5,6,7,8-Tetrahydro-1,2,4-triazolo[4,3-a]pyrazine-3-carboxylate is playing an increasingly important role. we look forward to future research findings about 723286-68-8.

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; BARDEN, Timothy Claude; SHEPPECK, James Edward; RENNIE, Glen Robert; RENHOWE, Paul Allan; PERL, Nicholas; NAKAI, Takashi; MERMERIAN, Ara; LEE, Thomas Wai-Ho; JUNG, Joon; JIA, James; IYER, Karthik; IYENGAR, Rajesh R.; IM, G-Yoon Jamie; (293 pag.)WO2016/44447; (2016); 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. 14508-49-7, name is 2-Chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C4H3ClN2

A mixture of chloropyrazine 3 (5.0 mmol) and HNR1R2 (10.0 mmol) was heated at 100 C. in a sealed tube for 15 h. The reaction mixture was cooled to room temperature, diluted with methylene chloride (50 mL), washed with saturated sodium bicarbonate solution (10 mL), dried over sodium sulfate and concentrated to provide the product 4, which could be purified by column chromatography, but was usually used in the next step without purification.; Prepared from 2-chloropyrazine and diethanolamine according to general procedure 2 providing the aminopyrazine (700 mg, quant.) as an oil; 1H NMR (300 MHz, CDCl3) delta 7.80-7.99 (dd, J=2.7, 1.5 Hz, 1H), 7.90-7.89 (d, J=1.5 Hz, 1H), 7.79-7.80 (d, J=2.8 Hz, 1H), 4.78 (br s, 1H), 2.80-2.79 (d, J=4.9 Hz, 3H).

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 14508-49-7.

Reference:
Patent; Alcon, Inc.; US2006/142307; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4774-14-5, 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

-Chloro-N-phenylpyrazin^-amine. 2,6-Dichloropyrazine (510 mg,3.4 mmol), palladium acetate (75 mg, 0.33 mmol), 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (405 mg, 0.7 mmol), potassium carbonate (4.6 g, 33.3 mmol), and aniline (0.3 mL, 3.3 mmol) were suspended in anhydrous dioxane (23 mL). The resulting mixture was degassed with nitrogen for 5 minutes and stirred at 9O0C for one hour. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (3 x 50 mL), and the organic layers were combined and dried over magnesium sulfate. After filtration, the solvent was removed in vacuo. The residue was purified by silica gel chromatography (0-60% ethyl acetate in hexanes) to give the title compound as a white solid (88 mg, 0.43 mmol, 13% yield); 1H NMR (DMSO-^6) delta 9.86 (s, IH), 8.17 (s, IH), 7.98 (s, IH), 7.63 (d, J= 10.0 Hz, 2H), 7.35 (t, J= 7.2 Hz, 2H), 7.03 (t, J= 6.8 Hz, IH); MS (ESI) MS (ESI) m/z 206.0 [M+ 1]+.

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, 2,6-Dichloropyrazine, other downstream synthetic routes, hurry up and to see.

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

233278-56-3, name is 5,6,7,8-Tetrahydro[1,2,4]triazolo[1,5-a]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. Quality Control of 5,6,7,8-Tetrahydro[1,2,4]triazolo[1,5-a]pyrazine

To a solution of (S)-N-((3 -(4-bromophenyl)-2-oxooxazolidin-5 – yl)methyl)acetamide (100.0 mg, 0.319 mmol), 5 ,6,7,8-tetrahydro-[ 1 ,2,4]triazolo[ 1 ,5-a]pyrazine (150.0 mg, 1.208 mmol) and Cs2CO3 (312.0 mg, 0.958 mmol) in 1,4-Dioxane (2 mL) was added 2nd generation ruphos precatalyst (12.4 mg, 0.0 16 mmol) under N2 atmosphere. The mixturewas stirred at 100C for 16 hours. The reaction mixture was concentrated to give a residuewhich was purified by reverse phase prep-HPLC to give (S)-N-((3-(4-(5,6-dihydro-[1,2 ,4]triazolo[ 1,5 -a]pyrazin-7(8H)-yl)phenyl)-2-oxooxazolidin-5 -yl)methyl)acetamide as solid. MS(ESI) m/z: 357.1 [M+Hj.

The synthetic route of 233278-56-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; YANG, Lihu; OLSEN, David B.; YOUNG, Katherine; SU, Jing; MANDAL, Mihir B.; SUZUKI, Takao; YOU, Lanying; (85 pag.)WO2017/66964; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem