Category: Pyrazines

123-32-0, 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 123-32-0 as follows.

A method for preparing 5-methylpyrazine-2-carboxylic acid by catalytic oxidation, firstly, diatomaceous earth, manganese chloride, sodium tungstate,Cobalt nitrate and distilled water were added to the reactor at the following element mass ratio: diatomaceous earth: Mn:W:Co:H2O=1:0.09:0.08:0.14:50,Magnetically stirring at room temperature to make it dispersed and uniformly adsorbed, and then removing water by evaporation.Adding a liquid silica sol with a total mass of 5% of the solid sample and kneading it into a small granular sample of 1-2 mm.The mixture was placed in a muffle furnace and calcined in an air atmosphere at 600 C for 5 hours to obtain Mn-W-Co/diatomaceous earth-supported catalyst particles.10 g of Mn-W-Co/diatomaceous earth catalyst particles were packed into a fixed bed microreactor reaction tube, and the reactor was heated to 330 C.The reaction raw material 2,5-dimethylpyrazine was introduced into a fixed bed reaction tube by bubbling with high-temperature steam at 10 ml/min.Oxygen is introduced into the reaction tube separately at 20 ml/min to cause catalytic oxidation of 2,5-dimethylpyrazine in the catalytic bed.The 5-methylpyrazine-2-carboxylic acid is produced and taken out of the reaction tube by water vapor, condensed, crystallized, and collected.Analysis of 5-methylpyrazine-2-carboxylic acid by gas chromatographyThe yield was 75.6%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 123-32-0, and friends who are interested can also refer to it.

Reference:
Patent; Lanzhou University; Dong Zhengping; (6 pag.)CN109369544; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 55557-52-3

(90 g, 645 mmol), CH3COOH (1 L) and Raney Ni (20 g) were added to a 2 Lautoclave successively. A reaction was carried out in the autoclave while the reaction solution was stirred under ahydrogen pressure of 1 MPa for 48 hours at atmospheric temperature. After the reaction was completed, the reactionsolution was filtered through diatomite, and a solution of HCl in MeOH (200mL, 6.0N) was used to wash diatomite The filtrate after being concentrated was poured into toluene and the obtained system was stirred, and was thenconcentrated again. The obtained mixture was stirred in MTBE (methyl tert-butyl ether) and was filtered. The filtercake was stirred in MTBE and MeOH and was then filtered to obtain intermediate 2 (40g, yield: 35%) as a brownsolid. LCMS showed a molecular ion peak (M+1) 144.0.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 55557-52-3, its application will become more common.

Reference:
Patent; Hangzhou Sanyintai Pharmaceutical Technology Co., Ltd.; Yin, Jianming; YIN, Jianming; LV, Yubin; LI, Bangliang; (36 pag.)EP3480199; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4858-85-9, 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. 4858-85-9, name is 2,3-Dichloropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of 2,3-dichloropyrazine (1.2 g, 8.05 mmol) and morpholine (700 mg, 8.05 mmol) in ethanol (10 mL) was refluxed overnight. The mixture was cooled to RT, diluted with ethyl acetate (30 mL) and washed with water (30 mL) followed by brine (40 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography to yield 1.57 g of the desired product; 1H NMR (300 MHz, CDC13) delta 3.46 (t, 7 = 6.9 Hz, 4H), 3.86 (t, 7 = 6.9 Hz, 4H), 7.91 (d, 7 = 2.4 Hz, 1H), 8.12 (d, 7 = 2.4 Hz, 1H).

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; GLENMARK PHARMACEUTICALS S.A.; DAS, Sanjib; GHARAT, Laxmikant Atmaram; HARDE, Rajendra Laxman; SHELKE, Sandeep Yadunath; PARDESHI, Shailesh Ramesh; THOMAS, Abraham; KHAIRATKAR-JOSHI, Neelima; SHAH, Daisy Manish; BAJPAI, Malini; (181 pag.)WO2017/21879; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, 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 63744-22-9. 63744-22-9

Intermediate Example 2-1 :Preparation of 6-bromo-8-methylsulfan l-imidazo[1 ,2-a]pyrazineTo a stirred suspension of intermediate example 1 -16,8-dibromo-imidazo[1 ,2-a]pyrazine (489 g, 1766 mmol) in MeOH (2900 mL) at -20 C was dropwise added a solution of sodium methan thiolate (225 g, 3214 mmol, 1 .8 eq) in 800 mL water. After stirring overnight, the clear solution was poured on 30 L water and the yellowish precipitate was filtered, washed with 3 L water and dried in vaccuo to yield 301 g 6-bromo-8-methylsulfanyl-imidazo[1 ,2-a]pyrazine (69.8 %). 1 H-NMR (300 MHz, d6-DMSO): delta = 8.64 (1 H, s), 8.00 (1 H, d), 7.66 (1 H, d2.54 (3H, s) ppm.

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 6,8-Dibromoimidazo[1,2-a]pyrazine.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80228; (2012); 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 5424-01-1 as follows. 5424-01-1

General procedure: Used for N-benzyl derivatives 1-8. The starting 3-aminopyrazine-2-carboxylic acid(Sigma-Aldrich, Schnelldorf, Germany; 2.2 g; 15.8 mmol) in methanol (250 mL) was cooled downto 0 C and concentrated H2SO4 (3.2 mL) was added. The reaction mixture was stirred for 48 h atrt. Subsequently the reaction mixture was poured into water (27 mL) and alkalized by NaHCO3(approx. 6.3 g) to pH = 7. The precipitate was filtered off and collected as white-brown solid toobtain methyl 3-aminopryzine-2-carboxylate [32]. Methyl 3-aminopyrazine-2-carboxylate (100 mg;0.65 mmol) in methanol (2 mL) along with substituted benzylamine (1.95 mmol; 3 equiv) and NH4Cl(10 mg; 0.19 mmol; 0.1 equiv) [33] were put into reaction tube used for microwave assisted synthesiswith a magnetic stirrer. Reaction was performed in a CEM Discover microwave reactor with a focusedfield in pressurized vials with the following settings: 130 C, 90 W and 40 min. The progress of thereaction was checked using TLC (Merck Silica 60 F254) developed by in hexane/ethyl-acetate 2:1 system.The reaction mixture was adsorbed to silica gel and purified by flash chromatography (Teledyne IscoInc.,) using silica (irregular, 40-63 m) as a stationary phase and gradient elution EtOAc in hexane0-100%, with respect to the expected lipophilicity of the product.

According to the analysis of related databases, 5424-01-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Bouz, Ghada; Semelkova, Lucia; Jand?ourek, Ond?ej; Kone?na, Klara; Paterova, Pavla; Navratilova, Lucie; Kubi?ek, Vladimir; Kune?, Ji?i; Dole?al, Martin; Zitko, Jan; Molecules; vol. 24; 7; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

767340-03-4, Name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, 767340-03-4, 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.

Into a flask was charged [Rh(cod)2]OTf (0.1 mmol) and (S) -Cy2-p-Tol-Biphemp (Ligand E) (0.1 mmol) under a nitrogen atmosphere. Degassed trifluoroethanol was then added (20 mL) and the mixture was stirred at room temperature for 1 h. Into a hydrogenator was charged the enamine amide 2-4 (1 mmol) and then degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 100 psig hydrogen gas at 20 ¡ãC for 20 h (94percent assay yield, 98percent ee). 1H NMR (300 MHz, CD3CN): No. 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2.68 (m), 2.49 (m), 1.40 (bs). Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13C NMR (CD3CN): 8 171.8,157.4 (ddd , JCF = 242.4,9.2, 2.5 Hz), 152.2 (major), 151.8 (minor), 149.3 (ddd; JCF = 246.7, 14.2,12.9 Hz), 147.4 (ddd, JCF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JCF = 38.8 Hz), 124.6 (ddd , JCF = 18.5, 5.9, 4.0 Hz), 120.4 (dd , JCF = 19.1, 6.2 Hz), 119.8 (q, JCF = 268.9 Hz), 106.2 (dd , JCF = 29.5,20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38.5 (minor), 36.9.; The following high-performance liquid chromatographic (HPLC) conditions were used to determine percent conversion to product: Column: Waters Symmetry C18, 250 mm x 4.6 mm Eluent: Solvent A: 0.1 vol percent HC104/H20 Solvent B: acetonitrile Gradient: 0 min 75percent A : 25percent B 10 min 25percent A : 75percent B 12.5 min 25percent A: 75percent B 15 min 75percent A : 25percent B Flow rate: 1 mL/min Injection Vol. : 10 muL UV detection: 210 nm Column temp.: 40 ¡ãC Retention times: compound 2-4: 9.1 min compound 2-5: 5.4 min The following high-performance liquid chromatographic (HPLC) conditions were used to determine optical purity: Column: Chirapak, AD-H, 250 mm x 4.6 mm Eluent: Solvent A: 0.2 vol.percent diethylamine in heptane Solvent B: 0.1 vol percent diethylamine in ethanol Isochratic Run Time: 18 min Flow rate: 0.7 mL/min Injection Vol.: 7 muL UV detection: 268 nm Column temp.: 35 ¡ãC Retention times: (R) -amine 2-5: 13.8 min (S)-amine: 11.2 min

Statistics shows that (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine is playing an increasingly important role. we look forward to future research findings about 767340-03-4.

Reference:
Patent; MERCK & CO., INC.; SOLVIAS AG; WO2005/97733; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-18-0, Name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 1458-18-0, 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.

The mixture of methyl 3-amino-5, 6-dichloropyrazine-2-carboxylate (4.4 g, 19.91 nMol) , 2- (4-fluorophenyl) -4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (3.07 g, 21.9 nMol) in dioxane (50 mL) and water (5 mL ) was added Na 2CO 3 (4.22 g, 39.82 nMol) and dppfPdCl 2 (2.84 g, 3.98 nMol) . Then the mixture was stirred at 100 for 1 h under N 2 atmosphere. Then the mixture was concentrated and residue was poured to water (100 mL) and then extracted with EA (100 mL x 3) . The organic solution was then concentrated to afford the crude product (5.5 g, 98%yield) as a yellow solid which was used for next step without further purification. MS m/z (ESI) [M+H] + = 282.2.

Statistics shows that Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 1458-18-0.

Reference:
Patent; DIZAL (JIANGSU) PHARMACEUTICAL CO., LTD.; QI, Changhe; TSUI, Honchung; ZENG, Qingbei; YANG, Zhenfan; ZHANG, Xiaolin; (399 pag.)WO2020/35052; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 6164-79-0

The 4- (3-CHLORO-4- (2-PYAZINYLMETHOXY) anilino) -5-fluoroquinazoline used as starting material was obtained as follows: Methylpyrazine carboxylate (8.5g) was stirred in water (200 ml) and sodium borohydride (11.65 g) was added in one portion, resulting in a vigorous exotherm. The reaction mixture was stirred vigorously for 30 minutes, and then ethanol (80 ML) and saturated potassium carbonate (150 ml) were added. The mixture was stirred for 30 minutes and then extracted with ethyl acetate (5 x 150 ml) and DCM (5 x 150 ml). The combined extracts were dried and concentrated to give pyrazin-2-ylmethanol as a yellow oil (5.43 g, 80%), which was used without purification; NMR spectrum (DMSO-D6) 4.65 (s, 2H), 5.57 (br s, 1H), 8.54 (d, 2H), 8.71 (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; WO2004/93880; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 3149-28-8, name is 2-Methoxypyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 3149-28-8

General procedure: A magnetically stirred solution of xanthate (2.0 equiv) and pyrazine (1.0 equiv) in 1, 2-dichloroethane (1.0mmol/mL according to the xanthate) was refluxed for 15min under a flow of nitrogen. Then dilauroyl peroxide (DLP) was added portionwise (20mol % according to the xanthate) every hour until total consumption of one substrate. The reaction mixture was then cooled to room temperature and the solvent was evaporated under reduced pressure. Unless otherwise specified, the crude product was purified by flash chromatography on silica gel.

The synthetic route of 3149-28-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Huang, Qi; Qin, Ling; Zard, Samir Z.; Tetrahedron; vol. 74; 40; (2018); p. 5804 – 5817;,
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. 19745-07-4, name is 2,5-Dichloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., 19745-07-4

Example 23Preparation of N-(2- ( (JS, 2S)-2-\ 1 -(5 -chloropyrimidin-2-yl)piperidin-4-yl] cyclopropyl } ethyl)-5 -( 1 H- 1 ,2,4-triazol- 1 -yl)pyrazin-2-amine,Step 1: 2-cMoro-5-flH–l.,2,4-triazol-1-yl’)pyrazine.2,5-Dichloropyrazine (298mg, 2.0mmol) and 1,2,4-triazole (145mg, 2.1mmol) were added in DMF (1OmL), then cesium carbonate was added and the reaction was at room temperature over night. Water (2OmL) was added, extracted with ethyl acetate (3OmL), second wash with brine (2OmL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil.(TM). silica gel cartridge eluting with 22percent ethyl acetate/hexanes to give the title compound as a white solid.LRMS calc: 181.58; obs: 182.21(M+1).

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; MERCK SHARP & DOHME CORP.; WOOD, Harold, B.; ADAMS, Alan, D.; SZEWCZYK, Jason, W.; ZHANG, Yong; YANG, Meng; WO2011/19538; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem