Pyrazines

Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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. 55557-52-3

A.1.11. Synthesis of 3-aryl-pyrazine-2-carboxylic acids:; A.1.11.1 3-p-Tolyl-pyrazine-2-carboxylic acid; 3-Chloropyrazine-2-carbonitrile (3.0 g; 21.5 mmol) was dissolved in dimethoxyethane (65 ml) and 4-tolylboronic acid (3.2 g; 23.65 mmol) was added, followed by the addition of K2CO3 (8.2 g; 59 mmol) and water (30 ml). The reaction mixture was deoxygenized with N2 (g) for 3 minutes followed by the addition of triphenylphosphine (842 mg; 3.2 mmol) and palladium(II)acetate (237 mg; 1.06 mmol). The reaction mixture was heated to 900C for 14 h, cooled to rt, diluted with EtOAc, filtered over a plug of celite and dried with magnesiumsulfate. The organic solvent was evaporated under reduced pressure to give 5.3 g of S-p-tolyl-pyrazine-l-carbonitrile. The intermediate nitrile was dissolved in MeOH (110 ml) followed by the addition of 4M aq NaOH (180 ml). The resulting mixture was heated to 85C for 14 h, cooled to rt and the MeOH was evaporated under reduced pressure. The residual aq. phase was acidified to pH=2 by the addition of cone. HCl and the precipitated product was filtered off, dissolved in DCM / EtOAc and dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 2.30 g of 3-p- tolyl-pyrazine-2-carboxylic acid. LC-MS: tR = 0.40 min; [M-H]+ = 213.14.

The chemical industry reduces the impact on the environment during synthesis 3-Chloropyrazine-2-carbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ACTELION PHARMACEUTICALS LTD; WO2009/104155; (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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., 486460-21-3

To a solution of (R)-3-[(tert-butyloxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)- butanoic acid (1.36 g, 4.080 mmol) in acetonitrile (20 ml) was added Diisopropylethylamine (2.47 g, 19.12 mmol) and 1 ,1-Carbonyl diimidazole (0.94 g, 5.82 mmol) at room temperature. The reaction mixture was stirred for 30 min at room temperature. S-iTrifluoromethylJ-S.ej.e-tetrahydro-l ,2,3-triazolo[4,3- a]pyrazine (0.750 g, 3.88 mmol) was added to the above reaction mixture at room temperature. The reaction mixture was heated to 65-70C for 22 h. After completion of the reaction, the mixture was concentrated under vacuum and the crude mass was dissolved in ethyl acetate (15 ml) and washed with 5% aqueous NaHC03 solution followed by twice with water (2 x 30 ml). The ethyl acetate layer was concentrated under reduced pressure to get crude mass and recrystallized from mixture of 10 % ethyl acetate and petroleum ether (50 ml) to get 1.5 g (82%) of tert-butyl{(1 R)-3-oxo-1 -(2,4,5-trifluorobenzyl)-3-[3-(trifluoromethyl)-5-6- dihydro[1 ,2,4] triazole[4,3-a]pyrazin-7(8H)-yl]propyl}carbamate.

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; PANACEA BIOTEC LTD; JAIN, Rajesh; RAO, Jagadeeshwar, R; RAO, Siripragada, Mahender; WO2012/35549; (2012); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

123-32-0, Adding some certain compound to certain chemical reactions, such as: 123-32-0, name is 2,5-Dimethylpyrazine, 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 123-32-0.

The title compound was synthesized by the reaction of 2,5-dimethylpyrazine with 4-(dimethylamino)benzaldehyde (Scheme 1). A solution of 2,5-dimethylpyrazine (0.5 g, 4.62 mmol) and the 4-(dimethylamino)benzaldehyde (2.3 g, 13 mmol) were dissolved in DMF and the mixture was cooled to 0 C. To this mixture potassium-tert-butanolate (1.55 g, 13 mmol) was added in small portions and the mixture was brought to ambient temperature. Stirring was continued until all starting material had been consumed (TLC). After the completion of the reaction, water was added, and the product was isolated by extraction with chloroform. The organic layer was concentrated in vacuum and the solid material obtained was recrystallized to give the product (1.4 g, 52%) as ared solid. The structure of the compound was confirmed by IR, 1HNMR and 13C NMR.

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 123-32-0.

Reference:
Article; Asiri, Abdullah M.; Alamry, Khalid A.; Pannipara, Mehboobali; Al-Sehemi, Abdullah G.; El-Daly, Samy A.; Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; vol. 149; (2015); p. 722 – 730;,
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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 486460-21-3

333 mg (1 mmol) of 3S-t-butoxycarbonylamino-4-(t-butyl-dimethyl-silanyloxy)- butanoic acid which was obtained from step (1) was added 192 mg (1 mmol) of 3-trifluoromethyl-5,6-dihydro-8H-[l,2,4]triazolo[4,3-a]pyrazine, and the resulting mixture was dissolved in dichloromethane. The reaction solution was cooled to 0C, and 162 mg (1.2 mmol) of HOBT was added, followed by stirring for 10 minutes and then addition of 288 mg (1.5 mmol) of EDC. After removal of an icebath, the reaction solution was stirred for abour 13 hours, and then the residue, which was obtained by concentration was purified by column chromatography (1:1 hexane: ethyl acetate) to give 0.27 g of the title compound in yield of 53%.[582] 1H NMR (CDCl3) delta 5.1-5.3 (IH, m), 4.9-5.1(2H, m), 3.9-4.3 (4H, m), 3.7-3.8 (2H, m), 2.6-2.9 (2H, m), 1.40(9H, s), 0.87 (9H, s), 0.03 (6H, s)[583] Mass (m/e) 508 (M+l)

The synthetic route of 486460-21-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LG LIFE SCIENCES, LTD.; WO2006/104356; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

98-97-5, The chemical industry reduces the impact on the environment during synthesis 98-97-5, name is Pyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

REFERENCE EXAMPLE 8-42-pyrazinemethanol (Compound CD)Step 1; To methanol (8.0 mL), thionyl chloride (2.08 mL) was added dropwise under a nitrogen atmosphere at -10 C. and the mixture was stirred at the same temperature for 30 minutes. To this, 2-pyrazinecarboxylic acid (1.00 g, 8.06 mmol) was added at the same temperature and the mixture was stirred at room temperature for 72 hours. The reaction mixture was concentrated, a saturated aqueous sodium bicarbonate solution was added to the residue, and extraction with ethyl acetate was performed, followed by washing with brine and drying over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol 19/1) to give methyl 2-pyrazinecarboxylate (969 mg, yield: 87%).1H-NMR (270 MHz, CDCl3, delta); 4.06 (s, 3H), 8.74 (dd, J=1.3, 2.3 Hz, 1H), 8.79 (d, J=1.3 Hz, 1H), 9.34 (d, J=2.3 Hz, 1H).

The chemical industry reduces the impact on the environment during synthesis Pyrazine-2-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Amishiro, Nobuyoshi; Fukuda, Yuichi; Kinpara, Keisuke; Mie, Motoya; Tagaya, Hisashi; Takahashi, Takeshi; US2011/237584; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19745-07-4,Some common heterocyclic compound, 19745-07-4, name is 2,5-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.

Step F: To a solution of 3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-l,4′- bipiperidin-2-one HC1 salt (500 mg, 1.2 mmol) and DIEA (0.52 mL, 3.0 mmol) in DMF (6 mL) was added 2,5-dichloropyrazine (264 mg, 1.8 mmol). The reaction was heated at 120 ¡ãC overnight. The reaction was cooled to ambient temperature and partitioned between water and ethyl acetate. The organic layer was separated and the aqueous washed with EtOAc. The combined organic layers were dried with MgS04 and concentrated. The crude residue was purified by column chromatography to give (S)-l’-(5-chloropyrazin-2-yl)-3-(2,5-difluoro-4- (methylsulfonyl)phenylamino)-l,4′-bipiperidin-2-one(0.37g, 0.73 mmol, 62percent) Mass spectrum (apci) m/z = 500.2 (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 2,5-Dichloropyrazine, its application will become more common.

Reference:
Patent; ARRAY BIOPHARMA INC.; AICHER, Thomas Daniel; BENCSIK, Josef Roland; BOYD, Steven Armen; CONDROSKI, Kevin Ronald; FELL, Jay Bradford; FISCHER, John P.; HINKLIN, Ronald Jay; PRATT, Scott Alan; SINGH, Ajay; TURNER, Timothy M.; WO2011/146335; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 6863-74-7 name is 6-Chloropyrazine-2-carbonitrile, 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. 6863-74-7

EXAMPLE II-16 In a mixture of 140 ml of acetonitrile and 280 ml of toluene were suspended 58 g of potassium fluoride (spray-dried) and 8.7 g f 18-crown-6-ether. After heating the suspension under reflux for one hour in an atmosphere of nitrogen gas, the acetonitrile and toluene were distilled off under atmospheric pressure. The residue thus obtained was suspended in 280 mL of acetonitrile, 23 g of 6-chloro-2-pyrazinecarbonitrile synthesised according to the method described in Acta Poloniae Pharmaceutica, Vol. 33, Pages 153-161 (1976) was added, and the mixture thus obtained was heated under reflux for one hour in an atmosphere of nitrogen. The reaction mixture was cooled to room temperature, 280 mL of ethyl acetate and 280 mL of water were added, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was distilled off under a reduce pressure. The residue was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=10:1] to obtain 10 g of 6-fluoro-2-pyrazinecarbonitrile as a white-colored solid product. IR (KBr) cm-1: 2244 1H-NMR (CDCl3) delta: 8.72(1H,d,J=8.1 Hz), 8.88(1H,d, J=3.7 Hz)

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

Reference:
Patent; Toyama Chemical Co., Ltd.; US2003/130213; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6164-79-0, Adding a certain compound to certain chemical reactions, such as: 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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 6164-79-0.

Methyl 3-oxo-3-(pyrazin-2-yl)propanoate: 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.

According to the analysis of related databases, 6164-79-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hoffmann-La Roche Inc.; Bhagirath, Niala; Brameld, Kenneth Albert; Kennedy-Smith, Joshua; US2013/90333; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

38557-72-1, 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. 38557-72-1 name is 2-Chloro-3,5-dimethylpyrazine, 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.

To a mixture of 2-chloro-3 , 5-dimethylpyrazine (2 g) and EtOH (20 mL) were added potassium vinyltrifluoroborate (2.067 g) and TEA (2.93 mL) at room temperature, and the mixture was stirred under nitrogen atmosphere. To the mixture was added PdCl2(dppf) (1.026 g) , and the mixture was refluxed for 2 h. The mixture was concentrated, and the residue was poured into water at room temperature, and the mixture was extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgS04 and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (1.650 g) ¡¤ XH NMR (300 MHz, CDC13) delta 2.51 (3H, s), 2.54-2.62 (3H, m) , 5.47-5.62 (1H, m) , 6.22-6.47 (1H, m) , 6.86-7.03 (1H, m) , 8.25 (1H, s) .

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-3,5-dimethylpyrazine, and friends who are interested can also refer to it.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; TAKAKURA, Nobuyuki; BANNO, Yoshihiro; TERAO, Yoshito; OCHIDA, Atsuko; MORIMOTO, Sachie; KITAMURA, Shuji; TOMATA, Yoshihide; YASUMA, Tsuneo; IKOMA, Minoru; MASUDA, Kei; WO2013/125732; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 27398-39-6 name is 3-Chloropyrazine-2-carboxylic acid, 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. 27398-39-6

[00142] A mixture of 19 (1.50 g, 9.49 mmols, 1.0 eq), 1-(4-fluorophenyl)ethanamine (2.64 g, 19.0 mmols, 2.0 eq) and K2C03 (3.93 g, 28.5 mmols, 3.0 eq) in NMP (30 mL) was degassed, purged with nitrogen, and stirred at 140 ¡ãC for 16 hours. The mixture was diluted with ethyl acetate (100 mL) and washed with 2 N aqueous HC1 (30 mL x 3). The organic layer was dried over Na2SO4, filtered, and concentrated, the residue was purified by recrystallization (Petroleum ether/ethyl acetate) to give the desired product 20 (2.00 g, 7.66 mmols, 80.6percent) as a white solid.[00143] LCMS: ESI-MS: m/z: 262.2 [M+H1 RT = 1.87 mm. (Method A).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Chloropyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; ALPHARMAGEN, LLC; PUTMAN, David, G.; DASSE, Olivier; HOGENKAMP, Derk; (154 pag.)WO2016/144792; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem