Pyrazines

Reference of 109-08-0, These common heterocyclic compound, 109-08-0, name is 2-Methylpyrazine, 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.

A 2.5 M hexanes solution of n-BuLi (18.0 mL, 45 mmol) was added to a -78 °C THF solution (60 mL) of ^-BuOK (5.1 g, 45 mmol) and diisopropylamine (6.3 mL, 45 mmol). After 5 min at -78 °C the yellow mixture was warmed to -40 °C. Neat methylpyrazine (2.7 mL, 30 mmol) was added and the mixture rapidly turned dark red. After 30 min at -40 °C the mixture was cooled to -78 °C and neat allyl bromide (7.6 mL, 90 mmol) was added. After 30 min at -78 °C water was added and the mixture was partially concentrated to remove volatile organics. The resulting mixture was extracted with dichloromethane and the combined organics were dried (Na2SO4), concentrated, and purified via column chromatography to give 2.2 g of 2-but-3-enyl-pyrazine.

The synthetic route of 109-08-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BARBAY, J., Kent; LEONARD, Kristi; CHAKRAVARTY, Devraj; SHOOK, Brian, Christopher; WANG, Aihua; WO2010/45012; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1111638-10-8, 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. 1111638-10-8, name is 3-Chloro-5H-pyrrolo[2,3-b]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Step 4: 3-chloro-5-methyl-5H-pyrrolo[2,3-b]pyrazine To a mixture of 3-chloro-5H-pyrrolo[2,3-b]pyrazine (2.0 g, 13.02 mmol) and potassium hydroxide ( 1.46 g, 26.04 mmol) in N,N-dimethylmethanamide (40 ml . ) was added iodomethane (3.70 g, 26.04 mmol). The reaction mixture was stirred at 25 C for 3 h and diluted with water (50 mL). The mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 40% ethyl acetate in hexane) affording 3-chloro-5-methyl- 5H-pyrrolo[2,3-b]pyrazine (2.0 g, 92%): H NMR (400 MHz, DMSO-d6) delta 8.47 (s, 1H), 7.94 (d, J =3.6 Hz, 1H), 6.72 (d, = 3.6 Hz, 1H), 3.82 (s, 3H).

The synthetic route of 3-Chloro-5H-pyrrolo[2,3-b]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; ESTRADA, Anthony; HUESTIS, Malcolm; KELLAR, Terry; PATEL, Snahel; SHORE, Daniel; SIU, Michael; (260 pag.)WO2016/142310; (2016); A1;,
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Pyrazine | C4H4N2 – PubChem

Reference of 43029-19-2, 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 43029-19-2 as follows.

To a solution of 3-amino-1H-pyrazin-2-one (298.39 mg, 2.69 mmol) in DMA (10 mL) was added NaH (179.03 mg, 4.48 mmol, 60% purity) at 0C. The mixture was stirred at 0C for 0.5 hr. (5-Fluoro-1-isobutyl-indol-2-yl)methyl methanesulfonate (0.67 g, 2.24 mmol) was added to the mixture, and the mixture was stirred at 0C for 1.5 hr. The reaction mixture was diluted with NH4Cl (5 mL) and extracted with EtOAc (5 mL × 3). The combined organic layers were washed with brine (5 mL × 2), dried over anhydrous Na2SO4, filtered and concentrated in vacuum to give a residue. The residue was purified by columnchromatography to afford 3-amino-1-[(5-fluoro-1-isobutyl-indol-2-yl)methyl]pyrazin-2-one (I-426) (0.2 g) as a brown gum

According to the analysis of related databases, 43029-19-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SITARI PHARMA, INC.; CAMPBELL, David; CHAPMAN, Justin; CHEUNG, Mui, H.; DIRAIMONDO, Thoams, R.; DURON, Sergio, G.; (615 pag.)WO2020/33784; (2020); A1;,
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Pyrazine | C4H4N2 – PubChem

21279-62-9, name is 3-Chloropyrazine-2-carboxamide, 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 21279-62-9

General procedure: The starting compound (1.27 mmol) was treated with 18 aliphatic amines, alicyclic amines or saturated heterocycles containing at least one nitrogen atom (2.54 mmol). Four reactions were completed by conventional heating methods. The conditions were 110 C, toluene as a solvent and pyridine (1.27 mmol) as a base. The reaction time was set to one hour. Then the reactions were completed using the microwave reactor with focused field and conditions used for syntheses were 140 C, 30 min,120 W, methanol used as a solvent and pyridine (1.27 mmol) as a base. They were set experimentally with respect to prior experience. The progress of reaction was monitored with TLC in system hexane/ethyl acetate (1:1). Then the mixture was separated by flash column chromatograph using gradient elution. Mobile phases were hexane and ethyl acetate again.

The synthetic route of 21279-62-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jandourek, Ondrej; Dolezal, Martin; Kunes, Jiri; Kubicek, Vladimir; Paterova, Pavla; Pesko, Matus; Buchta, Vladimir; Kralova, Katarina; Zitko, Jan; Molecules; vol. 19; 7; (2014); p. 9318 – 9338;,
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Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-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 6966-01-4, Recommanded Product: Methyl 3-amino-6-bromopyrazine-2-carboxylate

Example 12.2: Preparation of 3-amino-6-methylpyrazine-2-carboxylic acid methyl ester; 3-Amino-6-bromopyrazine-2-carboxylic acid methyl ester (1.0 g), palladium acetate (0.101 g), and S-Phos (2′-dicyclohexylphosphino-2,6-dimethoxy-l,l’-biphenyl) were placed in a flask, with toluene (15 mL) and water (3 drops). Methyl boronic acid (0.394 g) and potassium phosphate (1.71 g) were added and the reaction mixture was refluxed for 24 hours. After allowing the reaction mixture to cool, the mixture was diluted with aqueous hydrochloric acid (IM) and extracted with ethyl acetate. The solvent was evaporated and the residue was purified by column chromatography on silica gel (eluent: diethyl ether) to give 3-amino-6-methylpyrazine-2-carboxylic acid methyl ester as a yellow solid (0.1 14 g).1H NMR (CDCl3): 2.40 (s, 3H), 3.92 (s, 3H), 6.21 (bs, 2H), 8.03 (s, IH) ppm.

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, Methyl 3-amino-6-bromopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SYNGENTA LIMITED; WO2008/9908; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 33332-25-1, The chemical industry reduces the impact on the environment during synthesis 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

Step 1: methyl 5-{3-(cyanomethyl)-3-f4-(7-{f2-(trimethylsilyl)ethoxyJmethyl}-7H- pyrrolo[2,3-d]pyrimidin-4-yl)-lH-pyrazol-l-yl]azetidin-l-yl}pyrazine-2-carboxylate (R)-(+)-2,2′-Bis(diphenylphosphino)-l,l’-binaphthyl (0.065 g, 0.10 mmol) was added to a mixture of {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3- d]pyrimidin-4-yl)-lH-pyrazol-l-yl]azetidin-3-yl}acetonitrile dihydrochloride (0.50 g, 1.0 mmol), methyl 5-chloropyrazine-2-carboxylate (0.18 g, 1.0 mmol)(Ark Pharm, Inc., Cat. No.: AK-23920), and cesium carbonate (1.0 g, 3.1 mmol) in toluene (15.0 mL) under nitrogene, followed by palladium acetate (0.023 g, 0.10 mmol). The reaction mixture was stirred at 120C for 3 h. After cooled to r.t., the reaction mixture was filtered throught a pad of celite, washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by flashchromatography on a silica gel column with ethyl acetate in dichloromethane (0-70%) to afford the desired product (0.31 g, 55%). LCMS (M+H)+ : m/z = 546.3

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, Methyl 5-chloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; INCYTE CORPORATION; YAO, Wenqing; BURNS, David M.; ZHUO, Jincong; WO2012/177606; (2012); 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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 5049-61-6

Pyrazin-2-amine 4a (1 g, 10 mmol) was dissolved in 50 mL of ethylene glycol dimethyl ether, followed by addition of 50 mL of methanol and 3-bromo-2-oxo-propionate (2.30 g, 12 mmol). After stirring for 4 hours at room temperature, the reaction mixture was cooled to 0 C and stirred for 30 minutes until a solid precipitated. The reaction mixture was filtered, and the filter cake was washed with ether (10 mLx3). The solid was dissolved in 50 mL of anhydrous ethanol and the solution was refluxed for 4 hours. The reaction mixture was concentrated under reduced pressure, added with 100 mL of dichloromethane, washed successively with saturated sodium carbonate solution (40 mL) and saturated sodium chloride solution (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain ethyl imidazo[1,2-a]pyrazine-3-carboxylate 14a (0.55 g, yield 28.9%) as a brown solid. MS m/z (ESI): 192.1 [M+1]

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 5049-61-6.

Reference:
Patent; Jiangsu Hansoh Pharmaceutical Co., Ltd.; TANG, Pengcho; LI, Xin; LI, Xiangqin; CHEN, Yang; WANG, Bin; ZHU, Zhe; EP2604610; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 55557-52-3,Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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.

General procedure: Compounds 5-10 (Supplemental Figure 6A, Scheme 1), 12-15 (Supplemental Figure 6B, Scheme 2), and 17, 18 (Supplemental Figure 6C, Scheme 3) were prepared by a modified procedure as reported by Kayser F. et al. (ref 1) and Chen Z. et al. (ref. 2). To a solution of the corresponding thiol, or phenol 4 (0.85 g, 5.0 mmol) in 15 ml DMF (N, N-Dimethylformamide) 3-chloropyrazine-2-carbonitrile (0.66 g, 4.76 mmol) and Na2CO3 (1.01 g, 9.52 mmol), or substituted chrolopyridines, or chlorobenzenes, were added respectively and the resulting mixture was refluxed at 80 C for 12 h. The DMF was evaporated at reduced pressure and the compound A residue was recrystallized from ethyl acetate. The rest of the compounds were purified by flash chromatography on silica gel with ethyl acetate:hexanes (5-100% gradient).

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

Reference:
Article; Freeman, Lita A.; Demosky, Stephen J.; Konaklieva, Monika; Kuskovsky, Rostislav; Aponte, Angel; Ossoli, Alice F.; Gordon, Scott M.; Koby, Ross F.; Manthei, Kelly A.; Shen, Min; Vaisman, Boris L.; Shamburek, Robert D.; Jadhav, Ajit; Calabresi, Laura; Gucek, Marjan; Tesmer, John J. G.; Levine, Rodney L.; Remaley, Alan T.; Journal of Pharmacology and Experimental Therapeutics; vol. 362; 2; (2017); p. 306 – 318;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 313339-92-3, 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 313339-92-3 as follows.

Into a 25-mL round-bottom flask, was placed 3,5-dichloropyrazine-2-carbonitrile (450 mg, 2.59 mmol, 1.00 equiv), and acetic acid (10 mL), followed Raney Ni (50 mg) tfc was introduced into the reaction mixture. The resulting solution was stirred overnight at 50 C in an oil bath. The solid was filtered out and the resulting mixture was concentrated under vacuum to give 560 mg (crude) of 9-2 as a green solid

According to the analysis of related databases, 313339-92-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; IDEAYA BIOSCIENCES, INC.; BECK, Hilary, Plake; GONZALEZ-LOPEZ, Marcos; SUTTON, James, Clifford, Jr.; (86 pag.)WO2019/156989; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 939412-86-9, These common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, 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.

2a. Synthesis of N-((3-chloropyrazin-2-yl)methyl)-4-oxocyclohexanecarboxamide To a stirred suspension of 2-aminomethyl-3-chloropyrazine hydrochloride (3.89 mmol, 0.70 g) in dichloromethane (25 mL) at room temperature was subsequently added triethylamine (7.78 mmol, 1.08 mL), 0-(7-azabenzotriazol-1-yl)-1 ,1 ,3,3-tetramethyluroniumhexafluorophosphate (4.67 mmol, 1.77 g) and finally 4-oxocyclohexanecarboxylate (3.89 mmol, 553 mg). After stirring for 16 hours, the suspension filtered over decalite. The decalite was washed with dichloromethane. The filtrate was washed with water, dried (sodium sulfate) and concentrated in vacuo. The resulting crude product was purified by column chromatography on silica gel (ethyl acetate). The product was dissolved in dichloromethane, washed with water and concentrated in vacuo to afford 1.09 g of the title compound.H NMR (CDCl3, 400 MHz): delta 2.03 – 2.14 (m, 2H), 2.22-2.30 (m, 2H), 2.35 – 2.45 (m, 2H), 2.52 – 2.60 (m, 2H), 2.68 – 2.78 (m, 1 H), 4.73 (d, J = 4 Hz, 2H), 6.93 (brs, 1 H), 8.34 – 8.37 (m, 1 H), 8.46 (d, J = 2 Hz, 1 H).

Statistics shows that (3-Chloropyrazin-2-yl)methanamine hydrochloride is playing an increasingly important role. we look forward to future research findings about 939412-86-9.

Reference:
Patent; N.V. ORGANON; MAN de,, Adrianus Petrus Antonius; REWINKEL,, Johannes Bernardus Maria; JANS,, Christiaan Gerardus Johannes Maria; RAAIJMAKERS,, Hans Cornelis Andreas; WIJKMANS,, Jacobus Cornelis Henricus Maria; WO2011/95556; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem