Author: Jessica.F

Adding a certain compound to certain chemical reactions, such as: 56423-63-3, name is 2-Bromopyrazine, 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 56423-63-3, Computed Properties of C4H3BrN2

Preparation 133: 2-Chloro-4-(pyrazin-2-yl)aniline; [00303] To a mixture of 4-amino-3-chlorophenylboronic acid pinacol ester (0.1 10g, 0.434 mmol), 2-bromopyrazine (0.090 g, 0.56 mmol), 1 ,1 ‘- bis(diphenylphosphino)ferrocene)-dichloropalladium(ll) DCM complex (24 mg, 0.029 mmol) was added anhydrous DME (3.0 mL) followed by 2M aqueous sodium carbonate (0.53 mL, 1 .06 mmol). The microwave vial was heated at 75C for 40 minutes under microwave irradiation. Further catalyst (0.012 g) was added and the vial was heated at 90C for 25 minutes under microwave irradiation. Further 2-bromopyrazine (0.060g), catalyst (12 mg) and 2M aqueous sodium carbonate (0.25 mL) were added and the reaction mixture was heated at 90C for an additional 30 minutes under microwave irradiation. The reaction was partitioned between ethyl acetate (60 mL) and a saturated aqueous NaHC03 solution (15 mL). The organic layer was washed with a saturated aqueous NaHC03 solution (2 x 15 mL), dried (Na2S04) and concentrated in vacuo. The residue was purified using preparative TLC eluting with 7% ethyl acetate in CH2CI2. The product band was recovered and stirred with 2% MeOH in ethyl acetate / CH2CI2 (v/v; 1 :10) (20 mL). The silica was removed by filtration, washed with ethyl acetate / CH2CI2 (v/v; 1 :5) (2×5 mL) and acetone (3 x 4 mL) to give the title compound as an off- white solid (0.039 g, 44%). 1 H-NMR (500 MHz, DMSO-d6) 5.86 (s, 2H), 6.89 (d, J = 8.5, 1 H), 7.85 (dd, J = 2.1 , 8.5 Hz, 1 H), 8.02 (d, J = 2.1 Hz, 1 H), 8.44 (d, J = 2.5 Hz, 1 H), 8.57 (dd, J = 1 .6, 2.5 Hz, 1 H), 9.12 (d, J = 1 .5 Hz, 1 H).

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; CANCER RESEARCH TECHNOLOGY LIMITED; BAVETSIAS, Vassilios; ATRASH, Butrus; NAUD, Sebastien Gaston Andre; SHELDRAKE, Peter William; BLAGG, Julian; WO2012/123745; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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. category: Pyrazines

To a dry-ice / acetone cooled solution of scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), n-BuLi (2.5 M, 14.1 mL, 0.035 mol) was added dropwise for 30 min. After addition, the reaction was stirred at this temperature for 30 min, followed by dropwise addition of a solution of compound S4 (13.6 g, 0.04 mol) in THF (20 mL). The reaction mixture was stirred at this temperature for another 30 min and allowed to stir at room temperature for 16 h. Then the reaction was quenched with aqeuous NH4Cl (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10:1) to afford the title compound (6 g, yield 50.4%) and scheme 5-8 compound S4 (4.8 g) was recovered.

The synthetic route of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (508 pag.)WO2017/35409; (2017); 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. 4774-14-5, name is 2,6-Dichloropyrazine, A new synthetic method of this compound is introduced below., Recommanded Product: 2,6-Dichloropyrazine

EXAMPLE 5 2-amino-6-chloropyrazine 120 ml of water, 20.8 ml (0.31 mol, 4.6 eq) of an aqueous 28% ammonia solution and 10 g (0.067 mol, 1 eq) of 2,6-dichloropyrazine were successively added to an autoclave reactor. The autoclave was sealed and the mixture heated at 140 C. for 3 h, then left at room temperature for 60 h. The mixture was filtered, the precipitate washed with water, then vacuum dried. The reaction produced 5.4 g of a fine powder (yield: 63%). 1H NMR (CDCl3) delta (ppm): 7.88 (s, 1H, CH); 7.84 (s, 1H, CH); 4.68 (m, 2H, NH2). HPLC: t=1.07 min MS: 130 (MH+) HPLC purity: 100%

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; Maillet, Magali; Saniere, Laurent; Nicolai, Eric; Potin, Dominique; Langlois, Michel; US2005/267126; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 5049-61-6,Some common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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.

A mixture of 2-aminopyrazine (25 g, 262.9 mmol) and chloroacetaldehyde (50% solution in water, 50 ml, 394 mmol) was heated for 2 d at 100 C. in the presence of sodium hydrogen carbonate (33.1 g, 394 mmol). The reaction mixture was cooled to room temperature, and saturated potassium carbonate solution (100 ml) was added thereto. Extraction with dichloromethane was then carried out, and the organic phase was dried (Na2SO4) and concentrated. Purification was carried out by column chromatography (dichloromethane/methanol 95:5+5% NH4OH [35%]). Yield: 7.6 g (24%)

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gruenenthal GmbH; US2008/153843; (2008); 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. 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Formula: C6H5Cl2N3O2

General procedure: To a solution of methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate (1.0 eq.) in 2-propanol (5 mL/mmol), an appropriate primary or secondary amine(3-6 eq.) was added, and the reaction mixture wasrefluxed for 2 h.10) The solution was cooled to roomtemperature, concentrated under reduced pressure, andthe residue was purified by silica-gel column chromatography(Wako gel C-200, 30-40% ethyl acetate/n-hexane) to afford the series 1 intermediate (yield:32-95%). The regioselectivity of the nucleophilicsubstitution at the 5-position of the pyrazine ring wasconfirmed by an X-ray structural analysis (Fig. S1).

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

Reference:
Article; Murai, Masatoshi; Habu, Sayako; Murakami, Sonomi; Ito, Takeshi; Miyoshi, Hideto; Bioscience, Biotechnology and Biochemistry; vol. 79; 7; (2015); p. 1061 – 1066;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 912773-21-8, 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 912773-21-8 as follows.

A mixture of 2-bromo-5-chloro-pyrazine (1 g, 5.17 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-[(lS)-2,2,2-trifluoro-l- methyl -ethoxy ] pyridine (1.73 g, 5.17 mmol), CS2CO3 (3.37 g, 10.34 mmol) and Pd(dppf)Cl2 (567.41 mg, 0.78 mmol) in l,4-Dioxane (100 mL) and Water (10 mL) was stirred at 55 C under N2 for 5 hours. From LCMS, desired MS was observed and no starting material was remained. The solution was cooled to room temperature and concentrated to give a residue. To the residue was added water (50 mL), extracted with EtOAc (50 mL x 2). The combined organic phase was washed with water (50 mL), brine (50 mL x 2), dried over anhydrous Na2S04, filtered and concentrated to give the crude product. The crude product was purified by flash chromatography column on silica gel (EtOAc in PE = 0% to 5%) to give the product (1.4 g,4.35 mmol, 84% yield) as a solid. ‘H NMR (DMSO-c, 400MHz) 5H= 9.18 (s, 1H), 8.91 – 8.74 (m, 2H), 8.46 (dd, 1H), 6.05 – 5.99 (m, 1H), 1.53 (d, 3H).

According to the analysis of related databases, 912773-21-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; MARTINEZ BOTELLA, Gabriel; REDDY, Kiran; WITTMANN, Marion; (0 pag.)WO2019/232209; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4949-13-7, name is 2-Fluoropyrazine, 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. Formula: C4H3FN2

Example 65(4-cyclobutylpiperazin-1-yl)(7-(pyrazin-2-yl)-7-azaspiro[3.5]nonan-2-yl)methanone A mixture of Intermediate 7 (100 mg, 0.34 mmol), 2-fluoropyrazine (141 mg, 1.44 mmol), DIEA (0.6 mL, 3.44 mmol) and DMSO (1 mL) was heated to 130 C. for 30 min in a Biotage Initiator microwave oven. The reaction mixture was injected on a preparative HPLC UV using a high pH shallow gradient method (Mobile phase: 30-50% B; A: H2O with 15 mM NH4CO3 and 0.375% NH4OH v/v, B: CH3CN, 30 min. run) on XBridge Prep C18 OBD, 30¡Á150 mm, 10 mum, Waters reverse phase column, to provide title compound (76 mg, 59.9%) as a solid. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.59-1.68 (m, 2H) 1.68-1.82 (m, 4H) 1.91 (br. s., 2H) 1.99-2.12 (m, 4H) 2.13-2.24 (m, 2H) 2.30 (br. s., 4H) 2.74 (quin, J=7.52 Hz, 1H) 3.22 (quin, J=8.69 Hz, 1H) 3.39 (br. s., 2H) 3.45-3.53 (m, 2H) 3.54-3.62 (m, 2H) 3.65 (br. s., 2H) 7.79 (d, J=2.34 Hz, 1H) 8.03 (dd, J=2.73, 1.56 Hz, 1H) 8.14 (s, 1H); HRMS m/z calcd for C21H32N5O 370.2601 [M+H]+, found 370.2604.

The synthetic route of 4949-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; US2010/130477; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 32111-28-7, name is N-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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. Recommanded Product: 32111-28-7

To a stirred solution of N-methylpyrazin-2-amine (1 g, 9.2 mmol) in dimethyl sulfoxide (20 ml) / water (0.4 ml) at 10 C was added portionwise N-lodosuccinimide (4.1 g, 18.4 mmol). The reaction mixture was then allowed to warm slowly to room temperature and stirred at that temperature overnight. An additonal aliquot of N-lodosuccinimide (4.1 g,18.4 mmol) was then added at room temperature. After stirring for 7hr, the reaction mixture was poured onto ice (20 g). The precipitate was collected, washed with cold water (20 ml), and dried to provide the title compound (2.15 g, 65 %). 1H NMR (300MHz, DMSO-d6) 5(ppm): 8.14(s, 1 H), 6.69 (br, 1 H), 2.77(d, 3 H, J=4.5 Hz); ESI-MS(-):360.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 32111-28-7, its application will become more common.

Reference:
Patent; SYNGENTA PARTICIPATIONS AG; EDMUNDS, Andrew; MUEHLEBACH, Michel; STOLLER, Andre; LOISELEUR, Olivier; BUCHHOLZ, Anke; HUETER, Ottmar Franz; BIGOT, Aurelien; HALL, Roger Graham; EMERY, Daniel; JUNG, Pierre Joseph Marcel; LU, Long; WU, Yaming; CHEN, Ruifang; WO2015/715; (2015); 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. 72788-94-4, name is 2-Chloro-5-(hydroxymethyl)pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 72788-94-4

Triethylamine (4.17 mL, 3.0 mmol) and mesyl chloride (1.57 mL, 2.00 mmol) were added to a solution of (5-chloro-2-pyrazinyl)methanol (1.44 g, 10.0 mmol) in anhydrous THF (20 mL) at 00C. The mixture was stirred at 00C for 0.5 h then partitioned between EtO Ac/water. The organic fraction was dried (MgSO4) and the solvent was removed under reduced pressure to give the crude mesylate. The mesylate was dissolved in acetone (40 mL), sodium iodide (7.5 g, 50 mmol) was added and the mixture was refluxed for Ih. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc/water. The residue was chromatographed on silica gel (DCM) to give 2- chloro-5-(iodomethyl)pyrazine. Sodium hydride (60% w/w, 0.36 g, 9.0 mmol) was added to a solution of(S)-2-nitro-6,7-dihydro-5H-imidazo[2,l-b][l,3]oxa-zin-6-ol (0.93 g, 5.02 mmol) and 2-chloro-5-(iodomethyl)pyrazine (1.54 g, 6.05 mmol) in DMF (10 mL) at -78C. The mixture was stirred at 00C for 1 h and then quenched with ice. EtOAc (200 mL) was added, the organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with a gradient (0-5%) MeOH/EtOAc to give the title compound (1.015 g, 65%) as a white solid. APCI MS m/z 312.6 (M + H). 1H NMR (400 MHz, (CD3)2SO) delta 8.76 (d, J= 1.4 Hz, IH), 8.50 (d, J= 1.4 Hz, IH), 8.02 (s, IH), 4.85 (d, J = 13.7 Hz, IH), 4.81 (d, J= 13.7 Hz, IH), 4.70 (td, J= 12.1, 2.6 Hz, IH), 4.49 (bd, J= 12.0 Hz, IH), 4.29-4.38 (m, 2H), 4.25 (dd, J= 13.5, 3.3 Hz, IH).

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 72788-94-4.

Reference:
Patent; GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT; WO2009/120789; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 56423-63-3, 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 56423-63-3 as follows.

A mixture of ethyl 2-((diphenylmethylene)amino)acetate (6.0 g, 22.47 mmol), 2-bromopyrazine (7.1 g, 44.90 mmol), potassium carbonate (9.30 g, 67.40 mmol) and tetrabutyl ammonium iodide (8.10 g, 22.40 mmol) in N-methyl-2-pyrrolidone (25 mL) was heated in a sealed tube at 110 C. for 16 hours. The mixture was poured into water (100 mL) and extracted with ethyl acetate (3¡Á50 mL). The organic layers were washed with brine (25 mL) and dried over sodium sulfate. Removal of solvent under vacuum afforded crude product which was purified in Combi-Flash instrument using a gradient of methanol in chloroform. Yield: 4.90 g (63%). 1H NMR (300 MHz, DMSO-d6) delta: 1.16 (t, 3H), 4.07 (q, 2H), 5.26 (s, 1H), 7.18 (dd, 2H), 7.38-7.61 (m, 8H), 8.56 (d, 1H), 8.57 (d, 1H), 8.60 (s, 1H). MS (ES) MH+: 346.3 for C21H19N3O2.

According to the analysis of related databases, 56423-63-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AstraZeneca AB; BASARAB, Gregory Steven; GOWRAVARAM, Madhusudhan Reddy; HAUCK, Sheila Irene; ZHOU, Fei; US2014/206677; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem