Month: April 2021

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. 56423-63-3, name is 2-Bromopyrazine, A new synthetic method of this compound is introduced below., COA of Formula: C4H3BrN2

n-BuLi (25.4 ml_, 63.5 mmol, 2.5 M in hexane) was added drop wise to a -78 C solution of 2-bromopyrazine (10.1 g, 63.5 mmol) in toluene (150 ml_) under N2. After 10 min at -78 C, a solution of N-cyclobutylidene-2-methylpropane-2-sulfinamide (Preparation 50, 10.0 g, 57.71 mmol) in toluene (50 ml_) was added slowly. The resulting dark red solution was stirred for 1 hr at -78 C. The reaction was quenched by the addition of sat. NH4CI solution (10 ml_) and the reaction mixture dried (MgS04), filtered and concentrated in vacuo to give a brown oil. The crude product was purified by column chromatography on silica gel eluting with pet. Ether: EtOAc (100:0 to 0: 100) to MeOH: EtOAc (9:91 ) to afford the title compound as a yellow oil, 4.0 g, 27%. 1H NMR (400 MHz, CDCI3): delta 1 .21 (s, 9H), 1.86-1 .96 (m, 1 H), 2.08-2.19 (m, 1 H), 2.58-2.78 (m, 4H), 3.62-3.75 (br s, 1 H), 8.49 (d, 1 H), 8.56 (dd, 1 H), 8.80 (d, 1 H). LCMS m/z = 254 [M+H]+

The synthetic route of 56423-63-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; CASIMIRO-GARCIA, Agustin; STROHBACH, Joseph Walter; HEPWORTH, David; LOVERING, Frank Eldridge; CHOI, Chulho; ALLAIS, Christophe Philippe; WRIGHT, Stephen Wayne; (213 pag.)WO2018/11681; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 24241-18-7, 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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Step A: 5-Bromo-3-phenylpyrazin-2-amineTo a deoxygenated solution of 3,5-dibromopyrazin-2-amine (5.00 g, 19.8 mmol) in 1,4- dioxane (100 mL) was added potassium carbonate (8.20 g, 59.3 mmol), phenylboronic acid (2.17 g, 17.8 mmol) and Pd(dppf)Ci2 (1.45 g, 1.98 mmol). The resulting mixture was heated at 90 C for 4 h, then cooled and partitioned between water (50 mL) and EtOAc (50 mL x 2). The combined organic layers were dried over a2S04 and concentrated, and the residue was purified by column chromatography on silica gel (PE/EtOAc = 15/1, 10/1, 5/1) to give the title compound. MS: m/z = 249.9 (M + 1).

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; MITCHELL, Helen; FRALEY, Mark, E.; COOKE, Andrew, J.; CHEN, Yi-Heng; STUMP, Craig, A.; ZHANG, Xu-Fang; MCCOMAS, Casey, C.; SCHIRRIPA, Kathy; MCWHERTER, Melody; MERCER, Swati, P.; BABAOGLU, Kerim; MENG, Dongfang; WU, Jane; LIU, Ping; WOOD, Harold, B.; BAO, Jianming; LI, Chun Sing; MAO, Qinghua; QI, Zhiqi; (263 pag.)WO2015/148344; (2015); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 17231-50-4, name is 3-Amino-6-chloro-2-pyrazinecarbonitrile, 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 17231-50-4, Safety of 3-Amino-6-chloro-2-pyrazinecarbonitrile

To a solution of 19a (3 g, 20 mmol) in DCM (50 mL) at 0 C was successively added TiCl4(2.2 mL, 20 mmol) and tert-butyl nitrite (7.4 mL, 62 mmol). The reaction mixture was stirred at room temperature for 3 h. When the reaction was completed monitored by TLC, the solvent was evaporated and the residue was treated with water (50 mL) and then extracted with ethyl acetate (2 ¡Á 50 mL). The extract was dried over Na2SO4,and concentrated to give 8 as a white solid (2.8 g, yield 81%). 3,6-Dichloropyrazine-2-carbonitrile (8) Yield: 81%, white solid, M.p.: 93-94 C (Lit. 90-91 C,Li 2017). 1H NMR (400 MHz, CDCl3): delta 8.60 (s, 1H). 13CNMR (125 MHz, CDCl3):delta 149.82, 147.65, 147.03, 128.90,112.60. EI-MS m/z: 173 (M+, Cl35,Cl35,100), 175 (M+, Cl35,Cl37,65), 177 (M+, Cl37,Cl37,10).

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:
Article; Guo, Qi; Xu, Mingshuo; Guo, Shuang; Zhu, Fuqiang; Xie, Yuanchao; Shen, Jingshan; Chemical Papers; vol. 73; 5; (2019); p. 1043 – 1051;,
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. 109-08-0, name is 2-Methylpyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 2-Methylpyrazine

Butyllithium (1.6 M in hexane solution, 10 ml, 16 mmol) was added dropwise to a solution of diisopropylamine (2.25 ml, 16 mmol) in anhydrous THF (50 ml) at -20¡ãC under a nitrogen atmosphere. The mixture was stirred at -20¡ãC for 30 minutes and after cooling at -70¡ãC a solution of 2-methyl-pyrazine (1.47 ml, 16 mmol) in THF (10 ml) was added dropwise. After 15 minutes, a solution of 3-bromo-propionic acid ethyl ester (2.54 ml, 19.2 mmol) in THF (10 ml) was added and the mixture maintained at -70¡ãC for 2 hours and then stirred at room temperature overnight. The reaction was then quenched with a saturated solution of NH4Cl and extracted with ethyl acetate, the organic phase was dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (hexane/ ethyl acetate from 9/1 to 1/1 respectively) to give the title compound (1 g, 33percent yield). UPLC/MS: 195.1 (MH+).

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

Reference:
Patent; Neurotune AG; EP2098526; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 356783-16-9, The chemical industry reduces the impact on the environment during synthesis 356783-16-9, name is 3,6-Dichloropyrazine-2-carbonitrile, I believe this compound will play a more active role in future production and life.

3.48 g of 3,6-dichloro-2-cyanopyrazine (3) was mixed with 10 mL of dry dimethylsulfoxide,Dry potassium fluoride 5.23g and tetrabutylammonium bromide 2.15g mixed evenly, sealed heating,Control reaction temperature 55 , stirring reaction 3h, the reaction is completed and rushed into 10mL cold water,Extracted three times with ethyl acetate (20 mL * 3)The organic phases were combined, washed twice with saturated brine,The organic phase was dried over anhydrous sodium sulfate and filtered,To a solution of 1.49 g of pale yellow solid 3, 6-difluoro-2-cyanopyrazine (4)Yield 52.80%, m.p. 56-57 C.

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, 3,6-Dichloropyrazine-2-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Zhengzhou University; Li Mengyang; (6 pag.)CN107226794; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 486460-20-2, name is 3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine, 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 486460-20-2, Application In Synthesis of 3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine

To a solution of 3-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyrazine (1.60 g) in metanol (20 mL) was added a catalytic amount of Pd/C. The suspension was stirred under H2 for 5 h, and then filtered. The filtrate was concentrated in vacuo to give a residue, which was used for next step without further purification.

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; SUNSHINE LAKE PHARMA CO., LTD.; Zhang, Jiancun; Zhang, Yingjun; Zhang, Weihong; Liu, Bing; Zhang, Jiquan; Liu, Jinlei; Zhang, Lu; US2014/228361; (2014); 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. 944709-42-6, name is 6,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 944709-42-6

A solution of (2-fluorobenzyl)zinc(II) chloride (18.0 ml, 0.5 M in THF, 9.00 mmol) was added to a mixture of PdCl2(PPh3)2 (0.253 g, 0.360 mmol) and commercially available intermediate Int-7a (2.00 g, 7.20 mmol). The reaction was purged with nitrogen, sealed and heated to 50 C for 1 h. The reaction mixture was cooled to room temperature and directly purified by silica gel chromatography utilizing a gradient of 0-70% ethyl acetate in hexanes to afford intermediate Int-7b (1.49 g, 61%). 1H NMR: (500 MHz, DMSO-d6), d (ppm): 9.46 (s, 1H), 8.74 (s, 1H), 7.39 – 7.42 (m, 1H), 7.30 – 7.34 (m, 1H), 7.14 – 7.21 (m, 2 H), 4.56 (s, 2H). MS ES+ m/z = 307.1 [M]+, 309.0 [M+2]+,

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 944709-42-6.

Reference:
Patent; CYCLERION THERAPEUTICS, INC.; RENNIE, Glen, Robert; RENHOWE, Paul, Allan; NAKAI, Takashi; MERMERIAN, Ara; CUMBERBATCH, Helen; (99 pag.)WO2019/126354; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 939412-86-9,Some common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, molecular formula is C5H7Cl2N3, 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.

(e) (2S,5R)-benzyl5-(((3-chloropyrazin-2-yl)methyl)carbamoyl)-2-(hydroxymethyl)piperidine-1-carboxylate To a solution of (3S,6S)-1-((benzyloxy)carbonyl)-6-(hydroxymethyl)piperidine-3-carboxylic acid (0.78 g, 2.66 mmol) in 20 mL of DMF was added HATU (1.21 g, 3.2 mmol). After stirring for 30 min under N2, (3-Chloro-pyrazin-2-yl) methanamine hydrochloride (0.48 g, 2.66 mol) and Et3N (0.8 g, 7.98 mmol) was added. The reaction mixture was stirred at room temperature for 12 hours under N2. The mixture was partitioned between EA and water. The organic layer was washed with 1 N HCl and water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford (2S,5R)-benzyl 5-(((3-chloropyrazin-2-yl)methyl)carbamoyl)-2-(hydroxymethyl) piperidine-1-carboxylate (0.7 g, 63.0% yield). 1HNMR (400 MHz, CD3OD): delta=8.50?8.54 (m, 1H), 8.35 (d, J=2.4 Hz, 1H), 7.31?7.41 (m, 5H), 5.16 (s, 2H), 4.63 (s, 2H), 4.34?4.38 (m, 1H), 4.21?4.25 (m, 1H), 3.72?3.77 (m, 1H), 3.63?3.67 (m, 1H), 3.01?3.07 (m, 1H), 2.46?2.54 (m, 1H), 1.80?1.93 (m, 3H), 1.61?1.71 (m, 1H). MS (ESI): M/Z (M+1): 419.1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (3-Chloropyrazin-2-yl)methanamine hydrochloride, its application will become more common.

Reference:
Patent; KIM, RONALD M.; Liu, Jian; Gao, Xiaolei; Boga, Sobhana Babu; Guiadeen, Deodialsingh; Kozlowski, Joseph A.; Yu, Wensheng; Anand, Rajan; Yu, Younong; Selyutin, Oleg B.; Gao, Ying-Duo; Wu, Hao; Liu, Shilan; Yang, Chundao; Wang, Hongjian; US2014/206681; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 41110-29-6, 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. 41110-29-6 name is Methyl 3-methylpyrazine-2-carboxylate, 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.

To a solution of mixture of methyl 5-chloro-3-methylpyrazine-2-carboxylate and methyl 6-chloro-3-methylpyrazine-2-carboxylate (8.6 g, 46.1 mmol) and hydrogen peroxide urea adduct (8.1 g, 86 mmol) in DCM (100 mL) was added 2,2,2-trifluoroacetic anhydride (10.89 ml, 78 mmol) dropwise. The resulting mixture was stirred at RT for 2 h, during which LCMS indicated complete transformation to the desired products. The reaction was diluted with CH2Cl2and quenched with water. The aqueous layer was back-extracted with CH2Cl2 (2¡Á). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to give crude products 5-chloro-2-(methoxycarbonyl)-3-methylpyrazine 1-oxide and 5-chloro-3-(methoxycarbonyl)-2-methylpyrazine 1-oxide (8.83 g, 43.6 mmol, 95% yield). MS m/z=203.0 [M+H]. Calculated for C7H7ClN2O3: 202.0. The mixture of the crude products were used without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-methylpyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; LEWIS, Richard T.; ALLEN, Jennifer R.; BROWN, James; GUZMAN-PEREZ, Angel; HUA, Zihao; JUDD, Ted; LIU, Qingyian; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; US2015/38497; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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.

General procedure: (R)-4-N-Boc-2-methylpiperazine (665 mg, 3.32 mmol), 1-adamantoyl chloride (990 mg, 4.98 mmol), and DIEA (1.15 mL, 6.64 mmol) were dissolved in 2.0 mL of dichloromethane, and the reaction was monitored by LCMS. Upon completion, 5.0 mL of MeOH was added, and the mixture was concentrated in vacuo. The residue was purified by flash chromatography. The purified product was immediately dissolved in 1.0 mL of MeOH and excess 4 N HCl in dioxanes (4.0 mL, 16 mmol). Once the protecting group had cleaved as judged by LCMS, an aqueous solution of saturated sodium bicarbonate was added until the pH was basic. The mixture was extracted with dichloromethane, and the organic layers were concentrated in vacuo to afford 814 mg (94% yield) of adamantan-1-yl((R)-2-methylpiperazin-1-yl)methanone as a white solid. Adamantan-1-yl((R)-2-methylpiperazin-1-yl)methanone (355 mg, 1.35 mmol) and 2-cyano-3-fluoropyridine (1.42 mL, 5.41 mmol) were dissolved in 4.0 mL of NMP in a microwave reaction vial and heated in the microwave for 10 min at 250 C. The reaction mixture was purified via reverse phase chromatography (0.1% TFA in H2O/MeCN). The fractions containing the product were combined and neutralized by the addition of aqueous saturated sodium bicarbonate. The mixture was extracted with dichloromethane, and the organic layers were combined and concentrated in vacuo. The residue was dissolved in 1.0 mL of MeOH and 4 N HCl in dioxanes (3.0 mL, 12 mmol) and stirred for 2 h. The mixture was concentrated in vacuo to afford 212 mgs (39% yield) of the HCl salt as a yellow solid.

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:
Article; Lovell, Kimberly M.; Felts, Andrew S.; Rodriguez, Alice L.; Venable, Daryl F.; Cho, Hyekyung P.; Morrison, Ryan D.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.; Bioorganic and Medicinal Chemistry Letters; vol. 23; 13; (2013); p. 3713 – 3718;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem