Author: Jessica.F

Electric Literature of 5424-01-1, The chemical industry reduces the impact on the environment during synthesis 5424-01-1, name is 3-Aminopyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

Example 1139.1 1 153.14[0257] A slurry of 3-amino-2-pyrazinecarboxylic acid (15 gm, 0.108 moles) in dry methanol (250 mL) was stirred as concentrated sulfuric acid (10 mL, 18.4 gm, 0.188 moles) was added. The addition of the acid caused most of the solid to dissolve. The mixture was stirred at reflux, causing the formation of a clear yellow solution. This solution was stirred at reflux for 5 hours and was then stored at room temperature overnight. The solution was diluted with methylene chloride (500 mL) and was stirred as a solution of potassium carbonate (26 gm, 0.188 moles) in water (75 mL) was slowly added. After stirring for 15 minutes, the organic phase was separated from the aqueous phase and was dried over magnesium sulfate. After filtration to remove the drying agent, the solvents were removed under reduced pressure. The solid residue was recrystallized from isopropyl alcohol to provide the methyl ester as a tan powder in a yield of 7.22 gm (43.7%).

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

Reference:
Patent; JANUS BIOTHERAPEUTICS, INC.; LIPFORD, Grayson, B.; ZEPP, Charles, M.; WO2012/167046; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1174321-06-2, These common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, 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.

Example 24 N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide Prepared from (3R,6R)-6-(5-amino-2-fluorophenyl)-3,5,5-trifluoro-3,6-dimethylpiperidine-2-thione and 5-(difluoromethyl)pyrazine-2-carboxylic acid LC-MS (m/z) 446 (MH+) tR=0.52 minutes (Method A) 1H NMR (600 MHz, DMSO-d6) delta 11.03 (s, 1H), 9.37 (t, J=2.4 Hz, 1H), 9.09 (s, 1H), 7.89-7.80 (m, 2H), 7.26 (t, J=53.9 Hz, 1H), 7.18 (dd, J=11.9, 8.7 Hz, 1H), 6.34 (s, 2H), 2.62-2.51 (m, 1H), 2.29-2.14 (m, 1H), 1.71 (d, J=23.2 Hz, 3H), 1.68 (s, 3H)

The synthetic route of 1174321-06-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; H. LUNDBECK A/S; Juhl, Karsten; Marigo, Mauro; Tagmose, Lena; Jensen, Thomas; US2015/232449; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 768-05-8, 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. 768-05-8, name is Pyrazinoic acid hydrazide, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To the solution of pyrazine carboxylic acid hydrazide (0.55 g, 4 mmol) in methanol (30 mL) was added dropwise with continuous stirring, a solution of 2-benzoyl pyridine (0.73 g, 4 mmol) in the same solvent. The reaction mixture was then refluxed for 5 h. The solid product so obtained was filtered and recrystallised in hot methanol.

The chemical industry reduces the impact on the environment during synthesis Pyrazinoic acid hydrazide. I believe this compound will play a more active role in future production and life.

Reference:
Article; Devi, Jai; Batra, Nisha; Malhotra, Rajesh; Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; vol. 97; (2012); p. 397 – 405,9;,
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. 14508-49-7, name is 2-Chloropyrazine, A new synthetic method of this compound is introduced below., Recommanded Product: 2-Chloropyrazine

Step A Ethanol (13 ml) and 1.0M Na2CO3 (27.5 ml) were added to a suspension of 2-chloropyrazine (4.0 g, 34.6 mmole), 4-formylphenylboronic acid (6.8 g, 45.0 mmole), and tetrakis(triphenylphosphine)palladium(0) (2.0 g, 1.7 mmole) in toluene (55 ml). The mixture was refluxed for 18 hours then cooled, diluted with EtOAc, washed with NaHCO3, washed with brine, dried (MgSO4) and concentrated. Purification by chromatography (SiO2, 4:1 hexanes/EtOAc) yielded 6.2 g (97%) of 4-(2-pyrazinyl)benzaldehyde.

The synthetic route of 14508-49-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhu, Bin; Marinelli, Brett; Macielag, Mark J.; US2005/250713; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products 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.

Example 345-[(3-Cyanopyrazin-2-y[)amino]-N-(2-ethy[pheny[)-3-methy[- 1 ,2-thiazo[e-4- carboxamide A mixture of 5-amino-N-(2-ethy[pheny[)-3-methy[-1 ,2-thiazo[e-4-carboxamide [Intermediate 1] (150 mg, 0.57 mmo[, 1.4 eq), 3-ch[oropyrazine-2-carbonitri[e [CAS-RN: 55557-52-3] (57 mg, 0.41 mmo[, 1.0 eq) and cesium carbonate (307 mg, 0.94 mmo[, 2.3 eq) in 4.0 mL dioxane/DMF (7/1) was p[aced in a microwave via[ and f[ushed with argon. Then, pa[[adium(II) acetate (9 mg, 0.04 mmo[, 0.1 eq) andXantphos (24 mg, 0.04 mmo[, 0.1 eq) were added. The via[ was capped and the reaction mixture was stirred at an environmenta[ temperature of 110 C overnight. On coo[ing, the reaction mixture was partitioned between dich[oromethane and water. After fi[tration over Ce[ite, the organic phase was separated and concentrated in vacuo. The crude product was purified via preparative HPLC(method A) to give 47 mg (22 % yie[d of theory) of the tit[e compound.UPLC-MS (Method 1): Rt = 1.24 mm; MS (Elneg) m/z = 363 [M-H].1H-NMR (400 MHz, DMSO-d6): oe [ppm] = 1.11 (t, 3H), 2.61 -2.82 (m, 5H), 7.09-7.31 (m, 3H), 7.46 (d, 1H), 8.20 (s br, 1H), 8.77 (d, 1H), 11.72 (s br, 1H).

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:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; PRECHTL, Stefan; SIEMEISTER, Gerhard; WENGNER, Antje Margret; ACKERSTAFF, Jens; NOWAK-REPPEL, Katrin; BADER, Benjamin; LIENAU, Philip; STOeCKIGT, Detlef; WO2014/118186; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1190927-25-3, 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 1190927-25-3 as follows.

To a solution of 3-morpholin-4-ylmethyl-1 /-/-indol-6-ol sodium salt (130 mg, 0.51 mmol) and 2-chloro-thiazolo[4,5-]pyrazine (70 mg, 0.41 mmol) in DMF (1.4 ml.) was added CS2CO3 (43 mg, 0.12 mmol) and the resulting suspension was stirred (rt, 16 h). The reaction mixture was filtered and the solid was rinsed with EtOAc. The reaction mixture was concentrated in vacuo. The resulting residue was purified via reverse phase HPLC to provide the title compound as a white powder (38.3 mg, 26%). MS (ESI): mass calculated for Ci8H17N5O2S, 367.1 ; m/z found, 368.1 [M+H]+. 1H NMR (600 MHz, CDCI3): 8.51 (d, J = 2.6, 1 H), 8.32 (d, J = 2.6, 1 H), 8.21 (s, 1 H), 7.83 (d, J = 8.6, 1 H), 7.45 (d, J = 2.2, 1 H), 7.21 (d, J = 2.3, 1 H), 7.12 (dd, J = 8.6, 2.2, 1 H), 3.75-3.69 (m, 6H), 2.51 (s, 4H).

According to the analysis of related databases, 1190927-25-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BACANI, Genesis; CHROVIAN, Christa, C.; ECCLES, Wendy; FOURIE, Anna, M.; GOMEZ, Laurent; GRICE, Cheryl, A.; KEARNEY, Aaron, M.; LANDRY-BAYLE, Adrienne, M.; LEE-DUTRA, Alice; SANTILLAN, Alejandro; TANIS, Virginia, M.; WIENER, John, J. M.; WO2010/132599; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 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, 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 767340-03-4, SDS of cas: 767340-03-4

To degaussed 2,2,2-trifluoroethanol (TFE) (30 mL) were added Rhodium(I) chloride 1,5- cycloocatadiene complex (18.3 mg, 0.05percent) and (R)-(-)-l-[(S)-2- diphenylphosphino)ferrocenyl]ethyl di-tert-butylphosphine (44.2 mg, 0.11percent). The solution was stirred at room temperature, degaussed three times, and then stirred for one hour at room temperature.To 250 ml hydrogenator were added (Z)-3-amino-l-(3-(trifluoromethyl)-5,6-dihydro- [l,2,4]triazolo[4,3-a]pyrazyn-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-l-one (30 gr, 1 equivalent) and TFE (120 ml) at room temperature and the mixture was washed three times with nitrogen gas. The catalyst solution was added and the clear solution was washed three times with nitrogen gas and then with hydrogen gas. The mixture remained under hydrogen at constant pressure of 5 bar and heated to 550C. The mixture was stirred at 550C for 26 hours to obtain Sitagliptin base in TFE solution (optical purity by HPLC 76.9percent, purity by HPLC 91.5percent)Two reaction mixtures which were obtained according to the above procedure were combined and the solution was divided to 10 parts.7 parts of the solution, each contained ca~ 6 gr Sitagliptin were concentrated and Sitagliptin base was precipitated by addition of MTBE then filtrated by vacuum filtration. The combined mother liqueur from the crystallization experiments was concentrated. The residue was dissolved in isopropanol (40 mL) at room temperature, heated to 50¡ãC. A solution of phosphoric acid (85percent, 1.7 mL, ca ~1 eq) in isopropanol (20 mL) was added and the mixture kept stirring at 50¡ãC for one hour, then cooled gradually to 25 ¡ãC, and stirred at 25¡ãC over night.The product was isolated by vacuum filtration and dried at 40¡ãC vacuum oven over night to obtain Sitagliptin phosphate crystalline form VI (optical purity by HPLC 51.8percent, purity by HPLC 99.20percent).

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; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2009/120746; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 36070-75-4, 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. 36070-75-4, name is 5-Chloropyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 5-chloropyrazine-2-carbonitrile (280 mg, 2.0 mmol) in DMF was added 4-fluoro-1H-pyrazole (170 mg, 2.0 mmol), and potassium acetate (395 mg, 4.0 mmol). The mixture was stirred at the 100C for 4 hours. The reaction mixture was cooled to 20C, poured into brine (25 mL), and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated and purified by column chromatography (hexane: ethyl acetate = 5:1) to give 5-(4-fluoro-1H-pyrazol-1- yl)pyrazine-2-carbonitrile (310 mg, Yield 82%). The structure was confirmed by LC-MS.

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, 5-Chloropyrazine-2-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BLUEPRINT MEDICINES CORPORATION; BRUBAKER, Jason D.; GUZI, Timothy; WILSON, Kevin J.; DIPIETRO, Lucian V.; ZHANG, Yulian; WILSON, Douglas; FLEMING, Paul E.; (137 pag.)WO2018/17983; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[1,2-a]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. Application In Synthesis of 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine

Production Example 3 6,7-Difluoro-7-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)-1-(thiazol-2-yl)methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (compound No. 51) A mixture of 0.34 g of 1-(thiazol-2-yl)methyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 0.5 g of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine and 2 ml of N-methylpyrrolidone was stirred at 60 to 70 C. for 2 hours. After the reaction mixture was concentrated under reduced pressure, 10 ml of water was added to the residue, followed by extraction with chloroform (20 ml *3). After the extract was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was recrystallized from ethyl ether to yield 0.06 g of the title compound. Melting point: 210-213 C. Elemental analysis (for C20 H15 F2 N5 O3 S.1/2H2 O)

The synthetic route of 91476-80-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Chemical Industries, Ltd.; US5519024; (1996); A;,
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., COA of Formula: C4H2Cl2N2

To a solution of fert-butyl azetidin-3-ylcarbamate hydrochloride (LXXX) (2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9 mmol). To this mixture was added 2,6-dichloropyrazine (LXXXI) (1.428 g, 9.58 mmol) and the reaction was stirred at 95C for 3 h. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes?hexanes:EtOAc 1 : 1) to yield fert-butyl (l-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXXXII) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C12H17CIN4O2 mlz 285.1 (M+H).

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; SAMUMED, LLC; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; HOOD, John; (280 pag.)WO2017/23986; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem