Category: Pyrazines

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.

(1) Synthesis of 2-benzyloxy-6-chloropyrazine as an intermediate: 7.6 g of benzylalcohol was dissolved in 65 ml of benzene, and 2.8 g of 60% sodium hydride was added little by little to the solution under stirring not so as to foam too much at room temperature. After the addition, stirring was continued for 10 min. at room temperature, followed by reflux for 1 hour. Subsequently, the solution was cooled to 50 to 60 C., and added dropwise with a solution of 10 g of 2,6-dichloropyrazine in 65 ml of benzene for 10 min. Then, after reflux for 4 hours, the reaction was finished. After cooling below 10 C., about 100 ml of water was added, and the separated benzene layer was collected. The residue obtained by distilling off the solvent was purified by silica-gel column chromatography (developing solvent: n-hexane and ethyl acetate) to obtain 12.8 g of 2-benzyloxy-6-chloropyrazine as a colourless oil (yield: 86.5%) nD25 1.5818.

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; Nippon Kayaku Kabushiki Kaisha; US4791127; (1988); A;,
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. 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., name: Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate

A round bottomed flask was charged with methyl 6-amino 2,3-dichloro pyrazine 5-carboxylate (Aldrich, 25 g, 112.6 mmol), 2-S-ethyl piperazine (prepared as per Williams et al J. Med. Chem 1996, 39, 1345, 83% active, 15.7 g, 112.7 mmol), cesium carbonate (100 g, 300 mmol) and 1,4 dioxane (400 mL). The flask was equipped with a reflux condenser and heated to 80 C. After 12 hours the reaction was cooled, diluted with CH2Cl2 (200 mL), and filtered through celite. The filtrate was washed once with water and then concentrated to an oil. The crude product was purified by silica gel column chromatography (3% to 10% MeOH in CH2Cl2) to afford compound A3 (30.8 g, 91%). MS:M+H=300

The synthetic route of 1458-18-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Schering Corporation; US2007/82913; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6863-73-6, name is 3-Chloropyrazin-2-amine, 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. COA of Formula: C4H4ClN3

3-chloropyrazine-2-amine (1.29 g, 10 mmol)And chloroacetaldehyde (40% aqueous solution, 9.8 g, 50 mmol) were added to 30 mL of isopropanol, and heated under reflux overnight.The solvent was removed by rotary evaporation, and 30 mL of water was added to dissolve.Adjust pH = 7 with saturated sodium bicarbonate solution, extract with ethyl acetate (20mL * 3), combine the organic phases,It was washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated.1.07 g of a pale yellow solid was isolated through a silica gel column with a yield of 70%.

The synthetic route of 6863-73-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenzhen Tajirui Bio-pharmaceutical Co., Ltd.; Wang Yihan; Xing Qingfeng; Ai Yixin; (85 pag.)CN110272426; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 4858-85-9, A common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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.

2,3-dichloropyrazine (III-9) (500 mg, 3.36 mmol) and 4-chlorophenol (II-17)(431 mg, 3.36 mmol) was dissolved in DMF (10 mL)Potassium carbonate (557 mg, 4.03 mmol) was added,Followed by stirring at 90 C. for 15 hours. The reaction solution was cooled,Water was added and extracted with ethyl acetate.The organic layer was washed successively with water and saturated brine,The solvent was distilled off under reduced pressure.The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 100: 0 ? 85: 15) to obtain compound (IV-102)(Yield 809 mg, yield quantitative)As a white solid.

The synthetic route of 4858-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kaken Pharmaceutical Co., Ltd.; Watanabe, Atsushi; Sato, Yuki; ogura, Keiji Tamada; Tatsumi, Yoshiyuki; (283 pag.)JP2018/145180; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1082843-72-8, 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. 1082843-72-8 name is 6-Bromo-3-chloropyrazin-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.

6-bromo-3-chloropyrazin-2-amine (2g, 9.59 mmol) and methyl 2-hydroxyacetate (2.222 ml, 28.8 mmol) were suspended in Tetrahydrofuran (THF) (88 ml) under N2 at ambient temperature in a multi necked flask. Potassium tert-butoxide 1 M in THF (23.99 ml, 23.99 mmol) was added and the mixture was stirred under N2 and heated to 50C for 18hrs. The reaction was monitored by 2mins liquid chromatography-mass spectrometry (LCMS) (high pH). After 18hrs, starting material still present by LCMS. Potassium tert- butoxide 1 M in THF (9.59 ml, 9.59 mmol) was added and left to stir for an additional 1 hr. (0080) After a total of 19hrs, starting material consumed by LCMS. The mixture was allowed to cool to ambient temperature then partitioned between water (60ml) and ethyl acetate (60ml) (organic layer discarded). The aqueous layer was acidified to pH=4 with aq 2M HCI then extracted twice with ethyl acetate (60ml). The combined organic layers were washed with water (75ml) then dried by passing through a hydrophobic frit and evaporated under vacuum to give the crude material 6-bromo-2H-pyrazino[2,3- b][1 ,4]oxazin-3(4H)-one (1 .9618g, 7.93 mmol, 83 % yield, with a purity of 93 % by NMR) as a red/brown solid. Sample carried through to next step without further purification LCMS (2mins, high pH): V4100473-3 rt = 0.44 mins, MH- = 230 (0081) IH NMR (400 MHz, DMSO-de) d ppm 4.90 (s, 2 H) 7.92 (s, 1 H) 11.81 (s, 1 H)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromo-3-chloropyrazin-2-amine, and friends who are interested can also refer to it.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ALDER, Catherine Mary; EDWARDS, Lee J; HAYES, Jerome; EVANS, Rhodri Ll?r; MCKAY, Blandine Suzanne Jeanne; (21 pag.)WO2019/180634; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 55557-52-3, 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. 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: In a degassed solution of DME/H2O (2:1) (12mL/mmol of diazine), were successively introduced S-Phos (10mol%) and Pd(OAc)2 (5mol%). The solution was heated at 80C for 10min then sodium carbonate (4.0equiv), appropriate boronic acid (1.05 or 1.5equiv) and appropriate diazine (1.0equiv) were added. The solution was then refluxed (15min or overnight) under Ar. The resulting mixture was filtered on Celite and washed with ethyl acetate and water. The aqueous phase was then extracted three times with ethyl acetate. The combined organic phase was dried over MgSO4 and evaporated to dryness. The residue was purified by column chromatography (eluent: PE/EtOAc) to give the desired product.

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:
Article; Fresneau, Nathalie; Cailly, Thomas; Fabis, Frederic; Bouillon, Jean-Philippe; Tetrahedron; vol. 69; 26; (2013); p. 5393 – 5400;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 1082843-72-8, 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. 1082843-72-8, name is 6-Bromo-3-chloropyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

6-Bromo- 3-chloropyrazin-2-amine (2000 mg, 9.59 mmol) was dissolved in DCM (48 ml) followed by triethylamine (3.99 ml, 28.78 mmol), di-tert-butyl dicarbonate (4188.12 mg, 19.19 mmol), and N,N-dimethylpyridin-4-amine (87.91 mg, 0.72 mmol). The reaction was allowed to stir at room temperature for overnight. The crude material was washed with water, dried, filtered and concentrated. The crude material was dissolved in minimal DCM and loaded onto a 25 g prepacked silica loader and eluted off a 40 g column using 0-30% MeOH/DCM. The title compound XI was isolated and identified by LCMS and NMR. The product was a mix of mono and bis boc-protected material, mainly bis boc-protected as observed by NMR.

The chemical industry reduces the impact on the environment during synthesis 6-Bromo-3-chloropyrazin-2-amine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GILEAD SCIENCES, INC.; BLOMGREN, Peter, A.; CURRIE, Kevin, S.; KROPF, Jeffrey E.; LEE, Seung H.; LO, Jennifer R.; MITCHELL, Scott A.; SCHMITT, Aaron C.; XIONG, Jin-Ming; XU, Jiangjun; ZHAO, Zhongdong; WO2015/100217; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 313340-08-8,Some common heterocyclic compound, 313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, molecular formula is C7H7Cl2N3O, 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 mixture of 3,5-dichloro-6-ethylpyrazine-2-carboxamide (1.0 g) and DMF (15 mL), thionyl chloride (1 mL) was added at room temperature and stirred for 20 minutes. The reaction liquid was poured into ice-cold water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane) to give 3,5-dichloro-6-ethylpyrazine-2-carbonitrile (608 mg) as a slightly yellow oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, its application will become more common.

Reference:
Patent; Waters Technologies Corporation; US2012/40968; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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. COA of Formula: C9H16N2O2

DMSO (1.95 g, 1.64 mL, 25.0 mmol) was added dropwise to a solution of oxalyl chloride (1.52 g,1.05 mL, 12.0 mmol) in CH2Cl2 at -78 0C. After stirring at -78 0C for 15 min, 4-phenyl-l-butanol (1.50 g, 1.52 mL, 10.0 mmol) was added dropwise. After 15 min, triethylamine (5.05 g, 6.96 mL) was added dropwise. After warming to r.t. over 2 hours, water (50 mL) was added and the solution was extracted with CH2Cl2 (4 X 50 mL). The combined organic phase was washed with HCl (0.25 N, 3 X 50 mL), water (50 mL), saturated NaHCO3, and brine. The organic extract was dried over Na2SO4, concentrated, and passed through a short silica column (2 x 3 cm), eluted with CH2Cl2. Solvent was removed to give 4-phenylbutanal as a colorless oil (1.30 g, 87percent). 1H NMR (500 MHz, CDCl3) delta 9.76 (t, / = 1.5 Hz, 1 H), 7.31-7.27 (m, 2 H), 7.22-7.17 (m, 2 H), 2.67 (t, / = 7.5 Hz, 2 H), 2.46 (dt, J = 1.6, 7.32 Hz, 2 H), 1.97 (m, 2 H).[000199] To a solution of the bislactim (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.842 g, 1.792 mL, 10.0 mmol) in THF (20 mL) at -78 0C was slowly added n-BuLi (6.875 mL, 1.6 M in hexanes, 11.0 mmol) under Ar. After stirring at -78 0C for 20 min, A methyl iodide solution (1.562 g, 0.686 mL, 11.0 mmol) in THF (5 mL) was added. It was stirred at -78 0C for 2 h. A further portion of n-BuLi (6.25 mL, 1.6 M in hexanes, 10.0 mmol) was added at -78 0C and the solution was warmed to 0 0C. A solution of SnCl2 (1.0 g, 5.3 mmol) in THF (20 mL) was added and stirred at 0 0C for 15 min. After cooling to -78 0C, a 4-phenylbutanal solution (0.74 g, 5.0 mmol) was added. After the mixture was stirred at -78 0C for 3 h, it was warmed to r.t. and a phosphate buffer (pH 7.0, 0.10 M, 150 mL) was added with stirring for an additional 10 min. The mixture was filtered and the solid washed with ether. The aqueous phase was extracted with ether (3 X 50 mL) and the combined organic phase was washed with brine and dried over Na2SO4. Solvent was removed and the residue was purified by silica gel column chromatography (3 X 25 cm, hexanes: EtOAc 9:1) to give compound 65 as a colorless viscous oil (850mg, 49percent). 1H NMR (500 MHz, CDCl3) delta 7.28-7.25 (m, 2 H), 7.19-7.15 (m, 3 H), 3.94 (d, / = 3.5 Hz, 1 H), 3.70 (s, 3 H), 3.64 (s, 3 H), 3.59 (dt, J = 2.0, 10.3 Hz, IH), 2.66-2.60 (m, 2 H), 2.28-2.25 (m, 1 H), 1.99 (d, J = 10.0 Hz, 1 H), 1.95-1.85 (m, I H), 1.75-1.65 (m, I H), 1.60-1.52 (m, 1 H), 1.35 (s, I H), 1.33-1.23 (m, 1 H), 1.08 (d, / = 7.0 Hz, 3 H), 0.69 (d, / = 6.9 Hz, 1 H). ESIMS (MNa+) m/z 369.4.[000200] Compound 65 (692 mg, 2.0 mmol) is dissolved in acetonitrile (24 mL) containing HCl (0.50 M, 24 mL). After the mixture is stirred at r.t. for 12 h, the solvent is removed, the residue is dissolved in a NaOH solution (2.0 M, 20 mL) in MeOH (2OmL), and the progress of the reaction is monitored by TLC. The reaction mixture was neutralized with a solution of HOAc, and solvent is removed. The residue is purified by reverse phase HPLC to give desired product, compound 66, as an amorphous 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 109838-85-9, its application will become more common.

Reference:
Patent; FORBES MEDI-TECH (RESEARCH), INC.; WO2008/31032; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 54013-06-8, name is Ethyl 5-aminopyrazine-2-carboxylate, 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 54013-06-8, name: Ethyl 5-aminopyrazine-2-carboxylate

A mixture of aminopyrazine, 3-bromo-1,1,1-trifluoropropan-2-one and ethanol was heated in a microwave synthesizer at 180 C for 60 minutes. After cooling to room temperature, the solvent is removed and the dark brown residue is purified by flash chlromatography (silica, 30-60% ethyl acetate/hexanes) to give I-3 as a tan colored solid. 1H NMR (400 MHz, CDCI3) delta 9.24 (s, 1H), 8.99 (d, J= 1.4, 1H), 8.10 (s, 1H), 4.51 (q, J= 7.1, 2H), 1.46 (t, J= 7.1, 3H).

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; IRM LLC; NOVARTIS AG; CHATTERJEE, Arnab Kumar; NAGLE, Advait Suresh; PARASELLI, Prasuna; LEONG, Seh Yong; ROLAND, Jason Thomas; MISHRA, Pranab Kumar; YEUNG, Bryan KS; ZOU, Bin; WO2014/78813; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem