Category: Pyrazines

27398-39-6, Adding a certain compound to certain chemical reactions, such as: 27398-39-6, name is 3-Chloropyrazine-2-carboxylic acid, 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 27398-39-6.

3-Chloropyrazin-2-carboxylic acid (1 equiv.) was dissolved in abs. dichloromethane (10 ml/mmol), and triethylamine (3 equiv.) was added. After stirring at room temperature for 5 minutes, N,N-dimethylhydrazine (1.3 equiv.) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (1.5 equiv., 50percent solution in tetrahydrofuran) were added. The resulting reaction mixture was stirred at room temperature for a further 30 minutes, and then water, sat. sodium hydrogencarbonate solution and dichloromethane were added. The aqueous phase was repeatedly extracted vigorously with dichloromethane, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated. Final purification of the resulting crude product by column chromatography gave 3-chloro-N?,N?-dimethylpyrazine-2-carbohydrazide in the form of a colorless solid. 3-Chloro-N?,N?-dimethylpyrazine-2-carbohydrazide (250 mg, 1.25 mmol) was then dissolved in abs. N,N-dimethylformamide (10 ml) under argon, and sodium hydride (60 mg, 1.50 mmol, 60percent purity) was added at room temperature. Stirring at room temperature for 15 minutes was followed by the addition of 3-(2,6-difluorophenyl)propyl bromide (352 mg, 1.50 mmol), and the resulting reaction mixture was stirred under reflux conditions for two hours. After cooling to room temperature, sat. sodium hydrogencarbonate solution, water and dichloromethane were added. The aqueous phase was repeatedly extracted vigorously with dichloromethane, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated. Final purification of the resulting crude product by column chromatography gave 3-chloro-N-[3-(2,6-difluorophenyl)propyl]-N?,N?-dimethylpyrazine-2-carbohydrazide in the form of a colorless viscous oil (118 mg, 26percent of theory).

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, 3-Chloropyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BAYER CROPSCIENCE AKTIENGESELLSCHAFT; FRACKENPOHL, Jens; BOJACK, Guido; BRUeNJES, Marco; HELMKE, Hendrik; ADELT, Isabelle; LEHR, Stefan; BRUeCHNER, Peter; DITTGEN, Jan; SCHMUTZLER, Dirk; HEINEMANN, Ines; BICKERS, Udo; HILLS, Martin Jeffrey; RUIZ-SANTAELLA, Juan Pedro; STREK, Harry; DESBORDES, Philippe; (119 pag.)US2018/206495; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19838-07-4, These common heterocyclic compound, 19838-07-4, name is 3-Methylpyrazin-2(1H)-one, 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.

To a solution of 3-methylpyrazin-2-ol (1.5 g, 13.62 mmol) in anhydrous DMF (20 mL) was added N-bromosuccinimide (2.67 g, 14.98 mmol) at 0 C. The reaction mixture was slowly warmed to room temperature and stirred overnight. The resulting mixture was poured into water, and extracted with IPA/DCM (1/5). The combined organics were dried over anhydrous Na2S04, filtered then concentrated. The residue was purified by column chomatography with 80% ethyl acetate/hexanes to give the title compound as white solid (1.97 g, 10.42 mmol, 77% yield).Exact mass calculated for C5H5BrN20: 188.0, found: LCMS m/z = 189.0 [M+H]+; lU NMR (400 MHz, DMSO-i ) delta ppm 2.27 (d, J = 0.5 Hz, 3H), 7.73 (s, 1H), 12.3 (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 19838-07-4.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; JONES, Robert M.; HAN, Sangdon; BUZARD, Daniel J.; LEHMANN, Juerg; NARAYANAN, Sanju; YUE, Dawei; WO2011/127051; (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. 486460-21-3 name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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. 486460-21-3

The resulting product is dissolved in tetrahydrofuran (200 ml) and the solution is added in about 90 minutes to a solution obtained dissolving chloroacetyl chloride (28.6 g, 253 mmol) in tetrahydrofuran (200 ml), under N2 atmosphere and under stirring. The solution is left under stirring at 25C for 1 h. After completion of the reaction, a 25% NaOH solution (80 g) is added, the phases are separated and the aqueous phase is extracted with 2×100 ml of tetrahydrofuran. The solvent is concentrated under reduced pressure to obtain 160 g of a crude, which is added with methyl-tert-butyl ether (220 ml) and the solution is heated under reflux of the solvent mixture. The solution is cooled to 10C under strong stirring for 3h. The product (56.1 g, 209 mmol, 89% yield) is a white solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Dipharma Francis S.r.l.; EP2270009; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

113305-94-5, name is 5-Aminopyrazine-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. 113305-94-5

To 2-amino-5-cyanopyrazine (Ark Pharm Inc) (4.87 g, 40.5 mmol) and hydroxylamine hydrochloride (6.20 g, 89 mmol) in EtOH (30 mL) was added triethylamine (9.44 g, 93 mmol). The reaction was stirred at 80C for 1 h. The precipitate was filtered, washed with a small volume ethano and dried on high vacuum to give 5-amino-N’-hydroxypyrazine-2- carboximidamide (5.9 g, 38.5 mmol, 95% yield) as a yellow powder. HPLC RT = 0.593 min (Method A), ESIMS [M+H]+ = 154

Statistics shows that 113305-94-5 is playing an increasingly important role. we look forward to future research findings about 5-Aminopyrazine-2-carbonitrile.

Reference:
Patent; NOVARTIS AG; HEBACH, Christina; KALLEN, Joerg; NOZULAK, Joachim; TINTELNOT-BLOMLEY, Marina; WIDLER, Leo; WO2013/80120; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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

A mixture of K2C03 (3.4 g, 0.24 mmol), 2,4-difluoro-3-hexyloxy-5-(2-pyridyl)phenyl boronic acid (2.04 g, 6.1 mmol) and 2,5-dichloropyrazine (719 mg, 2.5 mmol) in a mixture of water (20 ml_), toluene (40 ml_) and ethanol (2 ml_) was deoxygenated by bubbling N2 through the mixture for 20 minutes. Pd(PPh3)4 (250 mg, 0.24 mmol) was then added and the mixture was heated under refluxed for 15 hours. Brine (40 ml_) was added and the phases were separated. The aqueous layer was extracted with ethyl acetate (3 x 20 ml_). The combined organic layers were dried over MgS04, filtered and evaporated to dryness. The product was purified by column chromatography (Si02, Petroleum ether/EtOAc, from 9/1 to 6/4). Colourless solid (630 mg, 38percent). 1 H NMR (400 MHz, CDCI3) delta 9.15 (d, 1 H, J = 2.0 Hz), 8.74 (ddd, 2H, J = 1.2 Hz, J = 5.2 Hz, J = 6.4 Hz), 8.39 (dd, 2H, J = 8.4 Hz), 7.78 (m, 4H), 4.23 (t, 4H, J = 6 Hz), 1.83 (q, 4H, J = 7.2 Hz), 1.34 (m, 4H), 1.36 (m, 8H), 0.90 (t, 6H, J = 7.2 Hz). 13C NMR (100 MHz, CDCI3) delta 152.40, 150.05, 146.85, 144.58, 144.46, 136.63, 125.49, 125.31 , 124.40, 124.32, 122.86, 121.34 (m), 75.57, 31.32, 30.10, 25.46, 22.68, 14.13.

The synthetic route of 2,5-Dichloropyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNIVERSITY OF NORTHUMBRIA AT NEWCASTLE; KOZHEVNIKOV, Valery; LANOE, Pierre-Henri; WO2014/23972; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

The chemical industry reduces the impact on the environment during synthesis 5049-61-6, name is Pyrazin-2-amine, I believe this compound will play a more active role in future production and life. 5049-61-6

2-Aminopyrazine (Aldrich, 20 g, 0.21 mol) was dissolved in 600 mL of CH2Cl2 and then cooled to 0 C. in an ice bath. To the resulting slurry was added N-Bromosuccinimide (Aldrich, 37.6 g, 0.211 mol) portion-wise over approximately 10 min. The slurry was allowed to mix in the ice bath for 1.5 hr. The slurry was then filtered through a bed of Celite. The bed of Celtite was washed with ~150 mL CH2Cl2. The filtrate was then concentrated in vacuo to solids. The resulting solids were purified by chromatography (silica, ethyl acetate/hexanes), producing 19.4 g (53%) of product. 1H NMR confirmed the structure of the desired product.

The chemical industry reduces the impact on the environment during synthesis 5049-61-6. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Boehm, Terri L.; Brown, David L.; Carroll, Jeffery N.; Chen, Yiyuan; Fobian, Yvette M.; Freskos, John N.; Gasiecki, Alan F.; Grapperhaus, Margaret L.; Heintz, Robert M.; Hockerman, Susan L.; Kassab, Darren J.; Khanna, Ish K.; Kolodziej, Stephen A.; Massa, Mark A.; McDonald, Joseph J.; Mischke, Brent V.; Mischke, Deborah A.; Mullins, Patrick B.; Nagy, Mark A.; Norton, Monica B.; Rico, Joseph G.; Schmidt, Michelle A.; Stehle, Nathan W.; Talley, John J.; Vernier, William F.; Villamil, Clara I.; Wang, Lijuan J.; Wynn, Thomas A.; US2005/9838; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, The chemical industry reduces the impact on the environment during synthesis 33332-29-5, name is 2-Amino-5-chloropyrazine, I believe this compound will play a more active role in future production and life.

General procedure: Method B is a modification of Method A and was performed under nitrogen atmosphere andwith extended work-up. Substituted benzoyl chloride (1.5 mmol, 1.2 equiv) was placed into the askunder nitrogen, diluted with dry DCM (5 mL) and dry pyridine (400 mg, 5 mmol, 4 equiv) was added.The mixture was mixed for 5 min under nitrogen. Then, 5-chloropyrazin-2-amine (162 mg, 1.25 mmol,1 equiv) dissolved in DCM (10 mL) was added dropwise over 10 min under nitrogen ow. The askwas closed by septum and stirred for additional 6 h. After reaction, the mixture was diluted with DCMto the final volume of 40 mL and washed with water (1 30 mL), 5% (m/m) aqueous NaHCO3 solution(1 30 mL), and brine (1 30 mL). The organic layer was dried over anhydrous Na2SO4 and adsorbedon silica (4 g) by evaporating the solvents under reduced pressure. Automated flash chromatographywas run using same conditions as described in Method A. If needed, the products were recrystallizedfrom hot EtOH (crystallization initiated by cooling and dropwise addition of cold water).

The chemical industry reduces the impact on the environment during synthesis 2-Amino-5-chloropyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Article; Zitko, Jan; Mindlova, Al?b?ta; Vala?ek, Ond?ej; Jand’ourek, Ond?ej; Paterova, Pavla; Janou?ek, Ji?i; Kone?na, Klara; Dole?al, Martin; Molecules; vol. 23; 9; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 19745-07-4

A mixture of methyl (R)-3-(3-amino-4-(((1 r,4R)-4-((tert-butyldimethylsilyl)oxy)cyclo hexyl)(isobutyl)amino)phenyl)butanoate (200 mg, 0.42 mmol), 2,5-dichloropyrazine (125 mg, 0.84mmol), Pd2(dba)3 (76 mg, 0.084 mmol), Xantphos (96 mg, 0.168 mmol) and CS2CO3 (273 mg, 0.84 mmol) in toluene (10 mL) was stirred at 100¡ãC under N2 atmosphere overnight. The resulting mixture was partitioned between EtOAc and H20. The organic layer was washed with brine, dried over Na2S04, filtered and concentrated to give the crude product which was purified by flash chromatography (silica gel, 0-10percent EtOAc in PE) to afford the title compound (170 mg, 68percent yield). LCMS (ESI) m/z calcd for C31 H49CIN4O3S1: 588.33. Found: 589.62/591 .59 (M/M+2)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19745-07-4, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; DE LA ROSA, Martha Alicia; KAZMIERSKI, Wieslaw Mieczyslaw; SAMANO, Vicente; (369 pag.)WO2018/116107; (2018); 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 24241-18-7 as follows. 24241-18-7

Step A: Preparation of ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3,5-dibrompyrazine (20 g, 79mmol) in dimethylcarbonate (133 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over a2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 %) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDCl3): delta =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm.

According to the analysis of related databases, 24241-18-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80232; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4858-85-9, A common compound: 4858-85-9, name is 2,3-Dichloropyrazine, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

To a solution of (?)-methyl 4-((benzhydrylimino)methyl)benzoate (67 g, 204 mmol) in THF (700 mL) was cooled to 0 C and added dropwise NaHMDS (244 mL, 244 mmol). The mixture was stirred at this temperature for 30 minutes, and added a solution of 2,3- dichloropyrazine (33.2 g, 224 mmol) in THF (40 mL). The reaction mixture was stirred at 0 C for 20 minutes and RT for 40 minutes. After the reaction was completed, the reaction mixture was extracted with EA and water. The organic layer was treated with 3M HC1 (500 mL) for 10 minutes. The phases were separated and the organic layer was extracted with 3M HC1. The aqueous was washed with EA and then alkalified with Na2C03 to pH = 9. The aqueous solution was extracted with EA and the combined organics were dried and concentrated to give methyl 4-(amino(3-chloropyrazin-2- yl)methyl)benzoate (46 g, yield 81 %). MS-ESI (m/z): 278 (M+l) + (Acq Method: 10-80AB_2min; Rt: 0.75 min).

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, 2,3-Dichloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; LIU, Shilan; YANG, Chundao; ZHENG, Shuling; WO2014/113942; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem