Month: February 2021

Application of 14508-49-7,Some common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, molecular formula is C4H3ClN2, 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.

2-Chloropyrazine (7.79 mL, 87 mmol, commercially available e.g. from Sigma- Aldrich or Haiso PharmChem) was dissolved in ethanol (50 mL), and hydrazine hydrate (6.85 mL, 218 mmol) was added. The solution was refluxed for 6 hours. The mixture was cooled to room temperature and the solvent was partially evaporated. The residue was diluted with water and extracted with 10% (v/v) of 2-propanol/Dichloromethane solution (5 extractions). The combined organic phases were then dried and evaporated to give a yellow solid which was triturated with diethyl ether to give 2-hydrazinopyrazine as a yellow solid (3.32 g).

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

Reference:
Patent; GLAXO GROUP LIMITED; DEAN, David Kenneth; MUNOZ-MURIEDAS, Jorge; SIME, Mairi; STEADMAN, Jon Graham Anthony; THEWLIS, Rachel Elizabeth Anne; TRANI, Giancarlo; WALTER, Daryl Simon; WO2010/125102; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4949-13-7, These common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, 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.

Step 5: N-((4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (8e) To a microwave vial were added N-((4S,6S)-4-(2-fluoro-5-hydroxyphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (95 mg, 0.229 mmol), 2-fluoro-pyrazine (24.74 mg, 0.252 mmol), cesium carbonate (90 mg, 0.275 mmol) in DMSO (459 muL). The vial was heated in microwave instrument at 100 C. for 30 min. After cooling to room temperature, water was added to the reaction mixture and precipitate was observed. After stirring for 10 min, the precipitate was collected by filtration, washed with water and hexane, dried in vacuum oven at 60 C. for 1 h to provide N-((4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (85 mg, 0.173 mmol, 75% yield) as off-white solid. MS m/z=493 [M]+. Calculated for C23H17F5N4O3: 492.4.

Statistics shows that 2-Fluoropyrazine is playing an increasingly important role. we look forward to future research findings about 4949-13-7.

Reference:
Patent; MINATTI, Ana Elena; LOW, Jonathan D.; ALLEN, Jennifer R.; CHEN, Jian; CHEN, Ning; CHENG, Yuan; JUDD, Ted; LIU, Qingyian; LOPEZ, Patricia; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; TAMAYO, Nuria A.; XUE, Qiufen; YANG, Bryant; ZHONG, Wenge; US2014/249104; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 312736-49-5, 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. 312736-49-5, name is 3,5-Dichloropyrazine-2-carboxylic acid belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

a) Synthesis of 3,5-dichloro-pyrazine-2-carboxylic acid methyl ester To a solution of 3,5-dichloro-pyrazine-2-carboxylic acid (0.50 g, 2.60 mmol) in dimethylformamide (8 ml) is added potassium carbonate (0.54 g, 3.90 mmol) at RT followed by the addition of methyl iodide (0.8 ml, 13.0 mmol). The resulting mixture is stirred at RT for 1 h. After completion of the reaction, the mixture is diluted with water (15 ml) and extracted with EtOAc (3*20 ml). The combined organic layers are washed with water (20 ml), brine (20 ml), dried over anhydrous sodium sulfate and evaporated in vacuo to get 3,5-dichloro-pyrazine-2-carboxylic acid methyl ester (0.45 g, 2.18 mmol, 84%), which is used in the next step without further purification.

The synthetic route of 3,5-Dichloropyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUeNENTHAL GMBH; LUCAS, Simon; Kuehnert, Sven; Bahrenberg, Gregor; Schroeder, Wolfgang; US2014/148454; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 957230-68-1, 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. 957230-68-1, name is 3,6-Dibromo-2-pyrazinecarboxylic Acid, This compound has unique chemical properties. The synthetic route is as follows.

Step 2: Synthesis of Intermediate 1a as described in the general reaction scheme; 3,6-Dibromo-pyrazin-2-ylamine Diphenylphosphorylazide (2.59 mL, 12 mmol) and triethylamine (1.67 mL, 12 mmol) are added to a solution of 3,6-dibromo-pyrazin-2-carboxylic acid (3.52 g, 12 mmol) in t-butanol (90 mL). The reaction is heated at reflux for 18 hours. The reaction is quenched with water, then concentrated in vacuo and taken up in DCM. The organic solution is washed with water and 1N NaOH, dried over anhydrous MgSO4 and concentrated in vacuo. The resultant solid is filtered through a pad of silica using EtOAc, then concentrated and TFA:DCM (4:1, 12 mL) is added to the solid and stirred for 30 min. The solution is concentrated in vacuo then neutralised with 1N NaOH and extracted with DCM. The organic layer is dried over anhydrous MgSO4 and concentrated in vacuo to give the product. 1H NMR (250 MHz, DMSO-d6) ppm 7.25 (br s, 2H), 7.68 (s, 1H); m/z (APCI) 254 (M+H)+; m.p 135-139 C.

The chemical industry reduces the impact on the environment during synthesis 3,6-Dibromo-2-pyrazinecarboxylic Acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; WIGERINCK, Piet Tom Bert Paul; ANDREWS, Martin James Inglis; De WEER, Marc Maurice Germain; SABOURAULT, Nicholas Luc; KLUGE, Stefan Christian; US2011/118269; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 4774-14-5, 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. 4774-14-5 name is 2,6-Dichloropyrazine, 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.

Step 1 To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (XLVI) (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 (XLVII) (1.428 g, 9.58 mmol) and the reaction was stirred at 95 C. for 3 hours. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes?hexanes:EtOAc 1:1) to yield tert-butyl(1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (XLVIII) (2.2882 g, 8.04 mmol, 84% yield) as a white solid. ESIMS found for C12H17ClN4O2 m/z 285.1 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,6-Dichloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Samumed, LLC; Hood, John; Kumar KC, Sunil; Wallace, David Mark; Mittapalli, Gopi Kumar; Hofilena, Brian Joseph; Mak, Chi Ching; Bollu, Venkataiah; Eastman, Brian; US2015/266825; (2015); 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. 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H4ClN3

To a solution of 8.-chioroimidazo[i ,2a1pyrazine (200 mg, I .3 mmol) in MeCN/DCE (3 mL/1,5 mL) was added N1S (293 mg, I .3 mmol) at RT. The mixture was refluxed overnight. TLC (50% EtOAc in petroleum ether) indicated that starting material disappeared, the mixture was poured into water (10 mL), extracted with EtOAc (10 mL x 3). The combined organic layerwas washed with water (1 0 mL) and brine (1 0 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the title compound (200 mg) as a brown solid, LRMS m/z (M-f-H) 279.1, 281.1 found, 279.1, 281.1 required.

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; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Doug C.; MENG, Na; LUO, Yunfu; (127 pag.)WO2016/101119; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 76537-18-3, 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. 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 3-bromo-5-chloro-pyrazin-2-amine (600 mg, 2.88 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (397.48 mg, 3.17 mmol), Cs2C03 (1.88 g, 5.76 mmol) and Pd(dppf)Cl2 (210.62 mg, 0.29 mmol) in 1,4-Dioxane (5 mL) and Water (0.50 mL) was stirred at 70 C for 16 hours. After cooling to r.t., the mixture was concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 20% to 40% to 60% to 80%) to give the product (200 mg) as a solid. *H NMR (400MHz, CDC13) _ = 7.90 (s, 1H), 4.55 (br s, 2H), 2.40 (s, 3H).

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-Bromo-5-chloropyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; REDDY, Kiran; MARTINEZ BOTELLA, Gabriel; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; (364 pag.)WO2018/98499; (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 312736-50-8 as follows. Computed Properties of C5H3Cl2N3O

107261 To a solution of 3,5-dichloropyrazine-2-carboxamide (Example 12, Step 2, 52 g, 0.27 mol) in acetonitrile (1 L) was added POC13 (146 g, 89 mL, 0.95 mol) at room temperature. The mixture was heated to 90-100 C for 4 h. The mixture was cooled to room tempetature and poured slowlyinto a vigorously stirring solution of saturated aq. NaHCO3. Evolution of gas was observed. The mixture was extracted with EtOAc (3 x). The combined organic layers were dried over sodium sulfate then concentrated under reduced pressure to give a residue. The residue was purified by silica gel chromatography (0-30% EtOAc in hexanes) to give the title compound as a pale yellow solid. ?H NIVIR (400 MHz, CDC13): ppm 8.64 (s, 1H): ?3C NMR (101 IVIFIz, CDC13) ppm 150.8,150.43, 143.24, 128.06, 113.06.

According to the analysis of related databases, 312736-50-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; FLX BIO, INC.; BECK, Hilary, Plake; BIANNIC, Berenger; BUI, Minna Hue, Thanh; HU, Dennis, X.; KETCHAM, John, Michael; POWERS, Jay, Patrick; REILLY, Maureen, Kay; ROBLES-RESENDIZ, Omar; SHUNATONA, Hunter, Paul; WALKER, James, Ross; WUSTROW, David, Juergen; YOUNAI, Ashkaan; ZIBINSKY, Mikhail; (396 pag.)WO2018/22992; (2018); 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. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 939412-86-9

Intermediate 11-14. Step 7 : N-((3-chloropyrazin-2-yl)methyl)-9.9-difluoro-6-oxooctahvdro-lH-quinolizine-3- carboxamide To a solution of 9,9-difluoro-6-oxooctahydro-lH-quinolizine-3-carboxylic acid (1.9 g, 8.15 mmol) in THF (40 ml) was added (3-chloropyrazin-2-yl)methanamine hydrochloride (2.2 g, 12.22 mmol), HATU (4.65 g, 12.22 mmol) and TEA (6.81 ml, 48.9 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was treated with EA (200 ml) and water (200 ml), the organic layer was dried over Na2SC>4, filtered and concentrated. The residue was purified by column chromatography on silica gel eluted with PE/DCM/THF = 1/1/1 to give N-((3-chloropyrazin-2-yl)methyl)-9,9-difluoro-6-oxooctahydro-lH-quinolizine-3-carboxamide. lH NMR (400 MHz, CDC13) delta ppm 1.63 – 1.85 (m, 2 H), 1.99 – 2.29 (m, 3 H), 2.32 – 2.81 (m, 5 H), 3.46 – 3.62 (m, 1 H), 4.33 – 4.98 (m, 3 H), 8.15 – 8.24 (m, 1 H), 8.30 – 8.40 (m, 1 H).

The synthetic route of 939412-86-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; KOZLOWSKI, Joseph, A.; ALHASSAN, Abdul-Basit; BOGA, Sobhana Babu; GAO, Xiaolei; GUIADEEN, Deodialsingh; WANG, Jyhshing; XU, Jiayi; YU, Wensheng; YU, Younong; CAI, Jiaqiang; LIU, Shilan; WANG, Dahai; WU, Hao; YANG, Chundao; (211 pag.)WO2016/109221; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 25911-65-3, name is 3-Aminopyrazine-2-carbonitrile, 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 25911-65-3, Safety of 3-Aminopyrazine-2-carbonitrile

b) 4-Amino-2-(isopropoxymethyl)pteridine Obtained using the procedure described in section c of Example 2, starting with 8.8 g (0.073 mole) of 3-amino-2-pyrazinecarbonitrile and 13.0 g (0.11 mole) of 2-isopropoxyacetamidine in 295 ml of absolute ethanol. Refluxing time: 4 hours. Yld: 4.5 g (28%), m.p. 139-141 C. (ethyl acetate). NMR (CDCl3): delta=1.3 (6H, d); 3.8 (1H, septet); 4.7 (2H, s); 8.2 (2H, peak exchangeable with CF3 COOD); 8.6 (1H, d);9.0 (1H, d).

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; Lipha, Lyonnaise Industrielle Pharmaceutique; US5167949; (1992); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem