Pyrazines

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. 33332-28-4, name is 2-Amino-6-chloropyrazine, A new synthetic method of this compound is introduced below., COA of Formula: C4H4ClN3

Synthesis Example 12-Amino-3,5-dibromo-6-chloropyrazine (4)To a solution of 2-amino-6-chloropyrazine (3) (8.00 g, 61.8 mmol) in acetonitrile (80 mL) was gradually added N-bromosuccinimide (NBS) (27.5 g, 155 mmol) at 0¡ã C.After elevating to room temperature, the mixture was stirred overnight (18 hours).To the mixture was added water and the product was extracted with diethyl ether (*3).The combined organic extract was washed successively with water (*1) and brine (*1), followed by drying over anhydrous sodium sulfate.After filtration and concentration under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=3/1) to give 2-amino-3,5-dibromo-6-chloropyrazine (4) (16.8 g, 58.5 mmol, 94.7percent) as a yellow solid. TLC Rf=0.31 (n-hexane/ethyl acetate=4/1); 1H NMR (500 MHz, CDCl3) delta 5.14 (s, 2H); 13C NMR (126 MHz, CDCl3) delta 120.7, 122.0, 146.1, 151.0.

The synthetic route of 33332-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY; JNC CORPORATION; US2012/232272; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, 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. Safety of Pyrazin-2-amine

Method B. To a suspension of 2-aminopyrazine (3 g, 31.6 mmol) in acetonitrile (50 mL) was added N-chloro-N-methoxy-4-methylbenzenesulfonamide (TSA, 8.2 g,34.7 mmol) in batches at room temperature. The reaction mixture was heated at 40 C for 4 h. Subsequently, the solvent was evaporated in vacuum and the residue was partitioned between ethyl acetate (50 mL) and saturated aqueous Na2CO3solution (20 mL). The organic layer was dried over anhydrous Na2SO4,decolorized with activated charcoal (0.8 g), and concentrated. The crude product containing ~ 5% dichlorinated impurity judged by TLC was purified by chromatography on silica gel eluting with PE/EA (10:1-2:1) to give a light-yellow solid (3.3 g, yield 80%).

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

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

Electric Literature of 4774-14-5, A common heterocyclic compound, 4774-14-5, name is 2,6-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.

Synthesis of ethyl 4-(3,5-dichloropyrazin-2-yl)benzoate (11b): 2,6-Dichloropyrazine (9) (149 mg, 1.0 mmol) in THF (2 mL) was added to a solution of TMPZnCl.LiCl (2) (1.3 M in THF, 0.85 mL, 1.1 mmol) at 25 C. and the reaction mixture was then stirred at this temperature for 30 min according to TP 2. Pd(dba)2 (17 mg, 3 mol %) and P(o-furyl)3 (14 mg, 6 mol %) dissolved in THF (2 mL), followed by the addition of ethyl 4-iodobenzoate (359 mg, 1.3 mmol), were then transferred via cannula to the reaction mixture. The reaction mixture was stirred at 25 C. for 1.5 h. with a sat. aq. NH4Cl solution (20 mL), extracted with diethyl ether (3¡Á50 mL) and driedanhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash-chromatography (CH2Cl2/n-pentane, 1:2) furnished compound 11b (251 mg, 87%) as a colourless solid.m.p.: 88.5-90.0 C.1H-NMR (300 MHz, CDCl3) delta: 8.59 (s, 1 H), 8.14 (d, J=8.6 Hz, 2 H), 7.84 (d, J=8.6 Hz, 2 H), 4.40 (q, J=7.2 Hz, 2 H), 1.40 (t, J=7.0 Hz, 3 H).13C-NMR (75 MHz, CDCl3) 6: 165.8, 150.1, 145.9, 142.0, 139.0, 131.6, 129.4 (2), 61.2, 14.3.MS (70 eV, El) m/z (%): 296 (32) [M+], 270 (24), 268 (38), 251 (100), 223 (26).IR (ATR) v (cm-1): 3086, 3005, 2985, 2359, 1966, 1708, 1611, 1569, 1537, 1507, 1482, 1466, 1446, 1423, 1408, 1366, 1310, 1283, 1263, 1190, 1175, 1140, 1131, 1114, 1098, 1028, 1021, 1009, 915, 858, 843, 786, 758, 719, 698, 657, 634, 621, 616, 610, 602.HRMS (El) for C13H10Cl2N2O2 (296.0119): 296.0119.

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Knochel, Paul; Mosrin, Marc; US2011/288296; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 59489-71-3, 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.

2-aminc-5-brcmcpyrazine (lOg, 57mmcl) and 1-brcmc-2,2-dimethcxy-prcpane (15 g) were dissolved in IPA (30 mL) and heated at 100 00 in a sealed tube for 3 days. The reactionwas quenched with sodium bicarbonate solution and filtered and extracted with ethyl acetate;the organic layer was dried over sodium sulphate and concentrated to give a brown solid that was used for the next step without further purification.

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:
Patent; MERCK PATENT GMBH; GARDNER, John Mark Francis; BELL, Andrew Simon; (87 pag.)WO2020/16235; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

119165-68-3, name is 2-(1H-Imidazol-2-yl)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. Product Details of 119165-68-3

Step 2: 2-(1-{[2-(Trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)pyrazine To a solution of 2-(4H-imidazol-2-yl)pyrazine (0.75 g, 5.1 mmol) in DMF (7 mL) was added sodium hydride (60% dispersion in oil, 0.42 g, 10.3 mmol) and the reaction stirred at 40 C. for 2 hours. [2-(chloromethoxy)ethyl](trimethyl)silane (1.71 g, 10.3 mmol) was added and the reaction was stirred at 40 C. for a further 3 hours The reaction mixture was partitioned between EtOAc and water and the layers separated. The aqueous layers was extracted with EtOAc (*2) and the combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (gradient 20-60% EtOAc in hexane) to give the title compound (0.88 g, yellow oil). 1H NMR (400 MHz, CDCl3) delta ppm: 9.47 (d, J=1.0 Hz, 1H), 8.36-8.59 (m, 2H), 7.26-7.28 (m, 1H), 7.24 (d, J=1.3 Hz, 1H), 5.96-6.00 (m, 2H), 3.53-3.61 (m, 2H), 0.86-0.94 (m, 2H), -0.10-0.05 (m, 9H).

The synthetic route of 119165-68-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD.; Dimopoulos, Paschalis; Hall, Adrian; Kita, Yoichi; Madin, Andrew; Shuker, Nicola Louise; US2014/11802; (2014); A1;,
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. 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, A new synthetic method of this compound is introduced below., SDS of cas: 55557-52-3

An aqueous K2CO3 solution (2.0 M, 30 mL) is added to a solution of 3-chloro- pyrazine-2-carbonitrile (21.5 mmol) and the respective phenylboronic acid (21.5 mmol) in DME (65 mL). Triphenylphosphine (3.21 mmol) and palladium(II) acetate (1.06 mmol) are added and the mixture is stirred at 900C for 16 h and allowed to reach RT. EtOAc is added and the mixture is filtered through Celite, dried over MgSO4 and concentrated in vacuo to give the respective carbonitrile derivative which is diluted with MeOH (100 mL) and aqueous NaOH solution (4.0 M, 160 rnL). The mixture is stirred at 85C for 16 h, cooled to RT and concentrated partially in vacuo to remove methanol. Water and cone, hydrochloric acid are added (pH ~ 2) and the obtained precipitate is filtered off. The residue is dissolved in a mixture of EtOAc and DCM, dried over MgSO4 and concentrated in vacuo to give the desired acid derivative.3-(3-Methoxy-phenyl)-pyrazine-2-carboxylic acid prepared by reaction of S-chloro-pyrazine-l-carbonitrile with 3-methoxybenzene- boronic acid. LC-MS (A): tR = 0.71 min; [M+H]+ = 231.5.

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; ACTELION PHARMACEUTICALS LTD; AISSAOUI, Hamed; BOSS, Christoph; BROTSCHI, Christine; KOBERSTEIN, Ralf; SIEGRIST, Romain; SIFFERLEN, Thierry; TRACHSEL, Daniel; WILLIAMS, Jodi T.; WO2010/44054; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 109-08-0, 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 109-08-0 as follows.

0351] To a solution of LDA (295 mL, 0.59 mol, 2 M in heptane/THF/ethylbenzene) in anhydrous THF (300 mL) cooled to -40 C. was added 2-methylpyrazine (48.5 mL, 0.531 mol) dropwise via an addition funnel. The reaction was allowed to warm to -20 C. and was stirred for 90 minutes when a solution of benzaldehyde (54 mL, 0.531 mol) in anhydrous THF (200 mL) was added dropwise via an addition funnel. After complete addition, the reaction was allowed to warm to room temperature and was stirred for 20 hours. The reaction was then cooled in an ice bath and saturated NH4Cl (500 mL) was added. The resulting mixture was extracted with EtOAc (500 mL, 250 mL). The combined extracts were dried (Na2SO4), filtered and concentrated to a damp, beige solid. The product was triturated with Et2O and collected then dried overnight to yield 56.0 g (53percent) of a light brown solid, mp 81-84 C.

According to the analysis of related databases, 109-08-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hendrix, James A.; Strupczewski, Joseph T.; Bordeau, Kenneth J.; Brooks, Sarah; Hemmerle, Horst; Urmann, Matthias; Zhao, Xu-Yang; Mueller, Paul J.; US2003/229066; (2003); 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. 21279-62-9, name is 3-Chloropyrazine-2-carboxamide, This compound has unique chemical properties. The synthetic route is as follows., name: 3-Chloropyrazine-2-carboxamide

General procedure: Compounds 1-6 were prepared according to conventional organic synthesis methods. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was dissolved in THF (20 mL) in a round bottom flask and after that treated with two equivalents of the corresponding benzylamine and an equimolar amount of triethylamine. The reaction was conducted with continuous stirring and heating (70 C) under reflux in an oil bath for 15 h. Compounds 7-15 were synthesised using a microwave reactor with a focused field. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was put into a thick-walled tube together with the corresponding benzylamine (2.54 mmol), pyridine (1.27 mmol), methanol (approx. 5 mL) and a magnetic stir bar and then sealed with a special cap. The reaction parameters were set according to the previously published paper as follows-140 C, 30 min, 200 W [29]. Reaction progress was checked by TLC (hexane:ethyl acetate-1:1). Regardless of the synthesis method used,all reaction mixtures were adsorbed on silica and subjected to preparative flash chromatography (hexane and ethyl acetate, gradient elution, detection wavelengths 260 nm and 280 nm). Products were recrystallized from ethanol or ethanol and water if necessary. All final substances were chemically characterized (1H-NMR, 13C-NMR, IR, melting point and elemental analysis).

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 21279-62-9.

Reference:
Article; Jandourek, Ondrej; Tauchman, Marek; Paterova, Pavla; Konecna, Klara; Navratilova, Lucie; Kubicek, Vladimir; Holas, Ondrej; Zitko, Jan; Dolezal, Martin; Molecules; vol. 22; 2; (2017);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 312736-49-5, 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. 312736-49-5 name is 3,5-Dichloropyrazine-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.

To a solution of 3,5-dichloropyrazine-2-carboxylic acid (0.304 g, 1.58 mmol) in MeOH (5 mL) and diethyl ether (5 mL) at room temperature was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 4.00 mL, 8.00 mmol). The reaction mixture was stirred at RT for 30 min and concentrated. Purification by flash column chromatography on silica gel (5% to 20% EtOAc in hexanes) gave methyl 3,5- dichloropyrazine-2-carboxylate (0.312 g, 1.51 mmol, 96%o yield) as a white solid. LC/MS (ESf) m/z = 207.0 (M+H) +

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

Reference:
Patent; AMGEN INC.; MINATTI, Ana Elena; LOW, Jonathan, D.; ALLEN, Jennifer, R.; AMEGADZIE, Albert; BROWN, James; FROHN, Michael, J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul, E.; LOPEZ, Patricia; MA, Vu Van; NISHIMURA, Nobuko; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert, M.; SHAM, Kelvin; SMITH, Adrian, L.; WHITE, Ryan; XUE, Qiufen; WO2014/138484; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 38557-72-1, A common heterocyclic compound, 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, molecular formula is C6H7ClN2, 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.

[0450] Preparation Example 104: Preparation of (3,5-dimethylpyrazin-2-yl)piperazine hydrochloride[0451][0452] Under a nitrogen stream, to a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium(II) acetate (225 mg), 2-(dicyclohexylphosphino)-2?,4?,6?-triisopropyl-1,1?-biphenyl (953 mg) and sodium tert-butoxide(2.7 g) was added toluene (40 mL), and the mixture was stirred with heating under reflux for 8 hr. After cooling,the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent wasevaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g). The obtained (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL)was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added ethyl acetate(100 mL), and the precipitate was collected by filtration to give the title compound (3.3 g).

The synthetic route of 38557-72-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; MAEDA, Kazuhiro; ENDOH, Jun-ichi; TARAO, Akiko; TASHIRO, Kaoru; ISHIBUCHI, Seigo; HIKAWA, Hidemasa; EP2565182; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem