Author: Jessica.F

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 1458-16-8 as follows. 1458-16-8

To a mixture under argon of 0.5 mmol of intermediate -if-,0.025 mmol of Cul and 1 mmol of potassium carbonate in a small thick glass reactor (Ace Tube) , are successively added 1 mL of isopropanol, 1 mmol of ethylene glycol and 0.75 mmol of thiophenol. The reactor is sealed with a Teflon stopper, placedunder magnetic stirring and heated two hours at 80C. The reaction mixture is cooled to room temperature and the thus obtained precipitate isolated through filtration, washed and recrystallized from hot methanol (yield : 88%)LCMS (IE, m/z): (M+1) 248; ?H NMR: oH ppm 400 MHz, DMSO: 7.19 -7.14 (3H, m, CHarom.) , 7.30-7.26 (2H, m, CHarom.) , 7.97 (1H, 5,CHarom)

According to the analysis of related databases, 1458-16-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PIERRE FABRE MEDICAMENT; KALOUN, El Bachir; BEDJEGUELAL, Karim; MORDANT, Celine; RABOT, Remi; TAMBURLIN, Isabelle; FOURNIER, Emmanuel; SCHMITT, Philippe; (74 pag.)WO2016/207345; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5049-61-6, Name is Pyrazin-2-amine, 5049-61-6, 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.

Step 1 Imidazo[1,2-a]pyrazine-2-carboxylic acid ethyl ester Ethyl bromopyruvate (62.9 g) was added to the DME (258 mL) solution of 2-aminopyrazine (24.8 g) at room temperature and stirred for 2.5 h. The reaction mixture was cooled to 0 C. and stirred for 30 min to afford a pale brown precipitate. The precipitate was filtered and washed with Et2O to give pale brown crystals. The suspension of the precipitate (66.1 g) in EtOH (1.29 L) was heated at reflux temperature to turn to clear solution. After refluxing for 2h, the reaction mixture was concentrated under reduced pressure, then mixed with CHCl3 and saturated NaHCO3aq. The mixture was filtered through a pad of Celite and the separated organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with CHCl3-MeOH (99/1~97/3), and collected fractions were concentrated under reduced pressure followed by recrystallization from CHCl3-Et2O. The titled compound was obtained as pale pink crystals. Yield: 10.9 g, 22%). 1H NMR(CDCl3) d 1.46(t, 3H, J=7.2 Hz), 4.49(q, 2H, J=7.2 Hz), 7.96(d, 1H, J=4.7 Hz), 8.08(dd, 1H, J=1.2, 4.7 Hz), 8.26(s, 1H), 9.21(d, 1H, J=1.2 Hz).

Statistics shows that Pyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 5049-61-6.

Reference:
Patent; Wyeth; US2004/132708; (2004); 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. 23229-25-6, name is 2,6-Dibromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., 23229-25-6

the molar ratio of Sodiummethoxide and dibromopyrazine is 5:1 placed into three-necked flask with astirrer and a thermometer, added 500ml of Distilled water, start the mixer andwith speed of 200r / min it was stirredfor 10min; After the mixing the mixture was placed at reflux apparatus , heatedup to 60 C, refluxed for 2h, , the collected reflux liquid was put into abeaker then placed in an ice-water bath , at 4 C under ice the precipitatewas allowed to stand for 2h, filtered toobtain precipitate and spare after rotary evaporation drying; The massconcentration of concentrated sulfuric acid is 98% and after drying as mentioned above the precipitatemass ratio is 12: 1 were mixed andtogether poured into a beaker of 500mL, after stirred with a glass rod for10min placed on the shaker and Oscillating reaction for 2 h ,then againadded 50mL of nitric acid solution with a mass concentration of 95% , continues to oscillate the reaction for 20minto obtain a mixed solution; The ratio of the mixed liquid and ammonia water is1:5, the ammonia water was poured into the above mentioned mixed solution, placedthe reaction solution on a magnetic stirrer, with speed of 600r / min it was stirred for 10s , afterwards reduce speed to200r / min and continue to stir for 30min. After completion of the stirring,400ml of anhydrous ethanol added into the mixture solution, placed intoultrasonic vibration device, ultrasonic vibration reaction for 1h, thentransferred to a distillation apparatus, heated to 60 C, ethanol was removedby distillation,for drying used vacuum freeze-drying machine and after crushingof solid particles; Take 1g of the above mentioned solid particles and put into100ml of beaker , added 15ml of glacial acetic acid and 10ml of hydrogenperoxide with a mass concentration of 30%, water bath warmed to 40 C, andafter the 6hrs of reaction filtrated to obtain precipitate and dried to obtain 2,6-diamino-3,5-dinitro-1-oxidepyrazine.

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; Changzhou University; CHEN, Xing-quan; (5 pag.)CN105399690; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

875781-43-4, 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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Step 5: Synthesis of 2-Bromo-7-iodo-5-(toluene-4-suIfonyl)-5H-pyrroIo[2,3-b]pyrazine.[0286] To a suspension of 2-Bromo-7-iodo-5H-pyrrolo[2,3-b]pyrazine (290 mg, 0.895mmol) in THF (5 ml) was added NaH (60%, 43 mg, 1.08 mmol) in one portion at 0 C.The resulting mixture was stirred for 20 minutes before a ‘solution of para-toluenesulfonylchloride (188mg, 0.98 mmol) in THF (2 mL) was added. The reaction mixture was thenstirred at room temperature for 3 hours. Solvents were removed and the resulting darkbrown residue washed with aqueous KOH, water and dried to afford the title compound(423 mg, 99% yield) as a light brown solid. .H-NMR (500 MHz, Patent; SGX PHARMACEUTICALS, INC.; WO2006/15124; (2006); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, 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. 55557-52-3

1-[3-(3-Chloro-phenyl)-acryloyl]-piperazine-2-carboxylic acid methyl ester (1.6 g, 5.18 mmol) was mixed with 3-chloro-pyrazine-2-carbonitrile (0.868 g, 6.22 mmol) and triethylamine (1.05 g, 10.36 mmol) in acetonitrile at 90 C. overnight. The reaction mixture was quenched water and extracted with dichloromethane. The product was purified by column chromatography with 50% ethyl acetate in hexanes to give 4-[3-(3-chloro-phenyl)-acryloyl]-3′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3-carboxylic acid methyl ester (white solid, 1.5 g, 70.3%).

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 55557-52-3.

Reference:
Patent; AstraZeneca AB; NPS PHARMACEUTICALS; US2007/49578; (2007); A1;,
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 274-79-3 as follows. 274-79-3

To a solution of imidazo[1,2-a]pyrazine (intermediate C) (2.8 g, 23.5 mmol) in AcOH (acetic acid) (200 ml) was added bromine (6 ml, 5 eq.) via addition funnel, with the reaction flask protected from light. After addition, the flask was sealed. The mixture was stirred at rt for 24 hr., 6 ml (5 eq.) of additional Br2 was added to the reaction mixture, which was further stirred at rt for 48 hr. The mixture was evaporated to remove Br2 and acetic acid, and the residue was dissolved in 10% IPA/DCM, washed with sat. Na2CO3 (300 ml). The organics were combined, dried and concentrated to afford 5.9 g (yield 97%) of 3,5-dibromo-imidazo[1,2-a]pyrazine. 1H-NMR (400 MHz, DMSO-d6) delta 9.05 (s, 1H), 8.09 (s, 1H), 7.99 (s, 1H). MS m/z 278 [M++1].

According to the analysis of related databases, 274-79-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sugen, Inc.; US2004/220189; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6164-79-0, These common heterocyclic compound, 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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.

Method 54; Pvrazine-2-carboxaldehyde oxime A IN solution of lithium aluminium hydride in THF (73. 8ml, 73.8mmol) was added to a suspension of methyl pyrazine-2-carboxylate (20g, 145mmol) in anhydrous THF (300. 0ml) at-78¡ãC keeping the reaction temperature below-72¡ãC. On completion of addition the reaction mixture was left to stir at-78¡ãC for a further 20 minutes and then quenched with glacial acetic acid (20. 0ml). The resulting mixture was warmed to room temperature and the volatiles removed by evaporation. The residue was dissolved in 3N hydrochloric acid (116ml) and extracted with DCM. The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate solution and the solvent evaporated. The residue was purified by chromatography on silica gel eluting with DCM/diethylether (100: 0 then 80: 20 and then 0: 100) to give pyrazine-2-carboxaldehyde (15.67g, 100percent). This was immediately dissolved in chloroform (200ml) cooled to 0¡ãC and hydroxylamine mono-hydrochloride (11. 02g, 159. 5mmol) and triethylamine (24. 2ml, 117. 4mmol) were added. The reaction mixture was then stirred at ambient temperature for 0.5 hour, and the solvent removed by evaporation. The residue suspended in diethylether (500ml) and the insolubles removed by filtration. The filtrate was evaporated and the residue purified by chromatography eluting with DCM/diethylether (100: 0 then 80: 20 and then 0: 100) to give the title compound (5. 5g, 31percent) as a solid. NMR (DMSO-d6) : 8.15 (s, 1H), 8.62 (dd, 2H), 8. 99 (s, 1H).

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 6164-79-0.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/40159; (2005); 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. 123-32-0 name is 2,5-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. 123-32-0

54 g (498 mmol) of 2,5-dimethylpyrazine (manufactured by Tokyo Chemical Industry Co., Ltd.) and 224 g (2.02 mol) of selenium dioxide were added to 840 ml of a mixed solution of pyridine and water (mixing mass ratio: 20/1) And the mixture was heated under reflux for 48 hours. The reaction solution was cooled to ambient temperature and filtered, and the filtration residue was washed with a mixed solution of pyridine and water (mixing mass ratio: 20/1), the filtrate and the washing solution were combined and the liquid was distilled off to obtain a solid It was.The resulting solid was dispersed in 2 M dimethylamine aqueous solution used as an extraction solvent, and residual solids were removed from the extract by filtration. By distilling off the solvent from the extract, 71 g (yield 85%) of 2,5-pyrazinedicarboxylic acid (3) was obtained.

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

Reference:
Patent; IHI Corporation; Waseda University; Sato, Yutaka; Kanomata, Norihiro; Yuchi, Takeshi; (19 pag.)JP2018/140981; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 6164-79-0, name is Methyl 2-pyrazinecarboxylate, molecular formula is C6H6N2O2, 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. 6164-79-0

a 2-Hydroxymethylpyrazine To methyl 2-pyrazinecarboxylate (1.80 g) in THF (60 ml) was added diisobutylaluminium hydride (1 M solution in THF; 39 ml) at -78 C. with stirring. The solution was allowed to warm to room temperature, and stirred for 24 h. The reaction was quenched with solid tartaric acid, then aqueous sodium potassium tartrate, and stirred for 30 min at room temperature. Saturated aqueous sodium hydrogen carbonate was added until the pH of the solution was >7. The solution was washed with ethyl acetate (3*200 ml), and the organic layers combined, washed with saturated sodium chloride solution (1*200 ml), dried (magnesium sulfate) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, eluent =5% methanol in dichloromethane) to yield 2-hydroxymethylpyrazine as a dark brown oil (0.16 g). 1H NMR (250 MHz, CDCs) delta3.42 (1 H, br s), 4.85 (2 H, s), 8.55 (2 H, m), 8.68 (1 H, s); MS (ES+) m/e 111 [MH+].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6164-79-0, its application will become more common.

Reference:
Patent; Merck Sharp & Dohme Limited; US6255305; (2001); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

356783-16-9, name is 3,6-Dichloropyrazine-2-carbonitrile, 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. 356783-16-9

A mixture of 8 (2.6 g, 15.0 mmol), KF (5.23 g, 90.0 mmol), tetrabutylammonium bromide (1.93 g, 6.0 mmol) was predried under vacuum over phosphorus pentoxide. The mixture was charged in a polytetrafluoroethylene bottle followedby the addition of dried DMSO (20 mL), and heated at 60 C for 2.5-3 h. The reaction mixture was cooled to room temperature, treated with water (80 mL) and extracted with diethyl ether (100 mL). The organic layer was washed with water (3 ¡Á 25 mL), dried over Na2SO4, and purified by chromatography on silica gel with PE/EA (50:1-10:1) as eluent to give 9 as a white solid (1.27 g, yield 60%). 3,6-Difluoropyrazine-2-carbonitrile (9) Yield: 60%. white solid, M.p.: 58-60 C (Lit. 56-57 C, Li 2017). 1H NMR (400 MHz, CDCl3)delta 8.35 (dd, J = 8.1,1.4 Hz, 1H). 13C NMR (125 MHz, CDCl3):delta 159.73-157.69(d, J = 255 Hz), 157.64-155.62 (d, J = 252.5 Hz), 135.09 (dd, J = 41.6, 11.0 Hz), 114.04 (d, J = 35.8 Hz), 110.62 (d,J = 9.1 Hz). EI-MS m/z: 141 (M+, 100), 122 (M+, -F, 50),96 (M+, -F, -CN, 50).

Statistics shows that 356783-16-9 is playing an increasingly important role. we look forward to future research findings about 3,6-Dichloropyrazine-2-carbonitrile.

Reference:
Article; Guo, Qi; Xu, Mingshuo; Guo, Shuang; Zhu, Fuqiang; Xie, Yuanchao; Shen, Jingshan; Chemical Papers; vol. 73; 5; (2019); p. 1043 – 1051;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem