Month: February 2021

Reference of 4949-13-7, 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 4949-13-7 as follows.

[0211] To a mixture of 4-(Aminomethyl)benzonitrile hydrochloride (1.6 g, 9.3 mmol, 1.0 equiv) and IPA (15.0 mL) in a microwave vial (20 mL) were added 2-fluoropyrazine (1.0 g, 10.2 mmol, 1.1 equiv) and DIPEA (2.9 g, 22.2 mmol, 2.4 equiv). The vial was sealed and heated at 170 C in a microwave reactor for 4 h, concentrated onto 10 g of silica, and purified by silica gel chromatography (80 g column, 0-10% MeOH in DCM) to provide 1.2 g (62%) of 4-((pyrazin-2-ylamino)methyl)benzonitrile as a pale yellow solid. LRMS (ES) m/z 211.2 (M+H). 1H-NMR (Methanol-^, 400 MHz, ppm) d 7.96 – 7.90 (m, 2H), 7.70 – 7.62 (m, 3H), 7.53 – 7.48 (m, 2H), 4.63 (s, 2H).

According to the analysis of related databases, 4949-13-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CYTOKINETICS, INC.; MORGAN, Bradley P.; VANDERWAL, Mark; CHUANG, Chihyuan; (0 pag.)WO2020/5888; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 98-97-5, name is Pyrazine-2-carboxylic acid, 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 98-97-5, COA of Formula: C5H4N2O2

To a solution containing 2-pyrazine carboxylic acid (10 g, 80.5 mmol) in dichloromethane (150 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC (18.5 g, 96.6 mmol) and 1-hydroxybenzotriazole HOBT (13.05 g, 96.6 mmol) and the resulting solution stirred at 25 C. for 30 minutes. Then 1-cyclohexylglycine methyl ester (16.7 g, 80.5 mmol) and Hunig’s base (31.24 g, 241 mmol) was added and the reaction mixture stirred for 2 hours. The reaction mixture was partitioned between water and dichloromethane. The organic layer was removed and dried over MgSO4, filtered and concentrated in vacuo and purified via flash chromatography using ethyl acetate/hexane (20/80 to 30/70) to give a foam (13.3 g, 60%). The product of the previous reaction (6.54 g, 24 mmol) was dissolved in ethanol and treated with 1N sodium hydroxide (35.4 mL, 35.3 mmol) at 25 C. for 4 hours. The mixture was neutralized with 10% HCl to pH 4 and extracted with dichloromethane. The organic layer was removed and dried over MgSO4, filtered and concentrated in vacuo to afford a foam (5 g, 81%).

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

Reference:
Patent; Abbott Laboratories; US2010/29686; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 330786-09-9,Some common heterocyclic compound, 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, molecular formula is C6H4Cl2N2O2, 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 1 A mixture of methyl 3,5-dichloropyrazine-2-carboxylate (1.30 g, 6.28 mmol) and sodium methoxide (0.5 M in MeOH, 13.8 mL) was stirred at room temperature for 2 h. The mixture was quenched with ice water and extracted with EtOAc (2 x). The combined extracts were dried over sodium sulfate, filtered and concentrated. Si02 column chromatography (5% to 100% EtOAc in hexane) in vacuo to afford compound 2K-2. MS for 2K-2: m/e = 203 (M+l).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3,5-dichloropyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WALSH, Shawn, P.; CUMMING, Jared, N.; HE, Shuwen; TAOKA, Brandon, M.; TRUONG, Quang, T.; WU, Wen-Lian; (122 pag.)WO2015/187437; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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 486424-37-7, category: Pyrazines

The 3-(lH-benzimidazol-2-yl)-5-bromopyrazin-2-amine used as a starting material was prepared as follows :-etaATU (7.3 g) was added to a mixture of 3-amino-6-bromopyrazine-2-carboxylic acid (4 g), 1,2-phenylenediamine (2.07 g), triethylamine (3.8 ml) and DMF (40 ml) and the reaction mixture was stirred at ambient temperature for 1 hour. The resultant mixture was poured into aqueous sodium hydrogen carbonate solution and the resultant precipitate was isolated. The material so obtained was dissolved in acetic acid (20 ml) and heated to 900C for 3 hours. The resultant mixture was evaporated and the residue was triturated under methylene chloride. There was thus obtained 3-(lH-benzimidazol-2-yl)-5-bromopyrazin-2-amine (2.7 g); NMR Spectrum: (DMSOd6) 7.29 (m, 2eta), 7.59 (d, IH), 7.76 (d, IH), 8.28 (s, IH), 13.05 (s, IH); Mass Spectrum: M-HH+ 292; RT 2.34 min.

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; ASTRAZENECA AB; WO2009/7390; (2009); A2;,
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. 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Quality Control of 6-Chloropyrazine-2-carboxylic acid

Example 25; N-(tert-Butyl)-6-chloropyrazine-2-carboxamide Thionyl chloride (1 mL, 13. 7 mmol) was added to a suspension of the acid (325 mg, 2 mmol) in toluene (5 mL). A drop of DMF was then added and after stirring at RT for 10 min. the mixture was heated at reflux for lh. The reaction was cooled to RT and toluene and excess thionyl chloride were removed under reduced pressure. Toluene (1 mL) was then added to the residue and this was removed under reduced pressure. This process was repeated, and then CtiCIz (10 mL) was added and the resulting solution cooled to QC. t-Butylamine (0. 45 mL, 4.3 mmol) and triethylamine (1.1mL, 8.0 mmol) were then added and the solution stirred at RT overnight. The solution was diluted with 10 mL) and H20 (10 mL) and the organic layer collected and washed with aq. Na2CA and then dried (Na2SO4). The solvent was removed in vacuo and flash chromatography of the residue using CH2Cl2-MeOH (95: 5) separated the pure product as an oil (290 (at) mg, 68 %).

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; CYTOPIA RESEARCH PTY LTD; WO2005/66156; (2005); 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 486424-37-7 as follows. Application In Synthesis of 3-Amino-6-bromopyrazine-2-carboxylic acid

To the 3L into the reaction bottle 50.1g II, 2L methanol. 0 – 5 C lower, to the slowly dropping 133g 98.3% concentrated sulfuric acid, then completing, heating up to 40 C, instead on invitation 48h to raw material II basic reaction end. turns on lathe does methanol, 0 – 5 C lower, adding 200 ml methanol, 500g ice water mixture, wherein the aqueous solution of sodium bicarbonate to pH=6 – 7 adds by drops full and adjusted to. Filtering, the filter cake 45 C vacuum drying 12h, get 43.2g brown solid III, yield 80.1%

According to the analysis of related databases, 486424-37-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nanjing Huawei Pharmaceutical Development Co., Ltd.; Bao Jinyuan; Huang Hui; Jiang Yuwei; Zhang Xiaoqing; (8 pag.)CN104496917; (2017); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 140914-89-2, A common heterocyclic compound, 140914-89-2, name is 2-(Pyrazin-2-yl)acetic acid, molecular formula is C6H6N2O2, 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.

Intermediate 34 (300 mg, 0.75 mmol), 2-(pyrazin-2-yl)acetic acid (120 mg, 0.87 mmol), HATU (600 mg, 1.59 mmol), N-Ethyldiisopropyl amine (0.3 ml, 2.17 mmol) were dissolved in DMF (4 ml). This mixture was stirred at rt for 1 h. Reaction mass was poured in to water to obtain a solid. Solid was filtered and purified the solid by column chromatography on 60-120 silica gel using MeOH and DCM (5:95) as eluent to afford the titled compound (13 mg) as a Pale-brown solid. M.P.: 232-234C. JH-NMR (delta ppm, DMSO-<, 400 MHz): 12.74 (s, 1H), 10.90 (s, 1H), 8.65 (s, 1H), 8.57-8.52 (m, 2H), 7.98 (d, J 9.8, 1H), 7.40-7.36 (m, 2H), 7.35-7.25 (m, 1H), 7.18- 7.12 (m, 2H), 4.30 (d, J 13.3, 2H), 4.06 (s, 2H), 3.79 (s, 2H), 3.40-3.31 (m, 1H), 3.05 (t, J 12, 2H), 2.10 (d, J 10.7, 2H), 1.80-1.66 (m, 2H). The synthetic route of 140914-89-2 has been constantly updated, and we look forward to future research findings. Reference:
Patent; RHIZEN PHARMACEUTICALS SA; BHAVAR, Prashant Kashinath; VAKKALANKA, Swaroop Kumar Venkata Satya; VISWANADHA, Srikant; SWAROOP, Merikapudi Gayatri; BABU, Govindarajulu; WO2015/101957; (2015); A2;,
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. 89283-32-9, name is (3-Chloropyrazin-2-yl)methanol, A new synthetic method of this compound is introduced below., Quality Control of (3-Chloropyrazin-2-yl)methanol

Under nitrogen protection,To a solution of 3-chloro-2-pyrazine methanol (60 g, 414.9 mmol)Triphenylphosphine (130.4 g, 497.9 mmol)And phthalimide (73.2 g, 497.9 mmol)Of the 500 mL THF solution,Was slowly added dropwise at -5 DIAD (100.6g, 497.9mmol),After complete addition, the reaction mixture was stirred at 20 3h,TLC shows that after completion of the reaction,Water was added to the reaction mixture and then extracted with EA (1 L x 3)The organic phase was dried sufficiently with anhydrous Na2SO4,After evaporation in vacuo, the residue was purified by flash chromatography (PE / EA = 30/1)To give 90.8 g of the title compound

The synthetic route of 89283-32-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chengdu Beite Pharmaceutical Co., Ltd.; Chengdu Hai Borui Pharmaceutical Co., Ltd.; Li Yingfu; Huang Haoxi; Liu Guanfeng; Chen Tonghun; Ren Junfeng; Su Zhonghai; (96 pag.)CN106831787; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 89123-58-0, The chemical industry reduces the impact on the environment during synthesis 89123-58-0, name is 5-Bromopyrazine-2,3-diamine, I believe this compound will play a more active role in future production and life.

Oxalyl chloride (3ml) was added to a solution of 5-({5-chloro-2-[(2-methylpropyl)oxy]- phenyl}methyl)-2-furancarboxylic acid (3.09g, lOmmol) and one drop of DMF in dichloromethane (30ml) and left at room temperature for one hour. The resulting solution was evaporated to dryness, azeotroped with toluene and the residue dissolved in dichloromethane (15ml) and added dropwise to a stirred solution of 2,3-diamino-5- bromopyrazine (2.08g, 11mmol) and 4-dimethyaminopyridine (100mg, 0.82mmol) in pyridine (20ml) and stirred for one hour. The solution was evaporated and the residue dissolved in ether/water. The organic phase was dried with magnesium sulphate, evaporated and chromatographed on silica gel eluting with ethyl acetate/hexane (15:85) to give 3.35g of white solid which was dissolved in acetic acid (40ml) and stirred and refluxed for 5 days. The resulting solution was evaporated, dissolved in ethyl acetate and washed with 2M sodium hydroxide solution. The organic phase was dried with magnesium sulphate, evaporated and purified by flash chromatography on silica eluting with ethyl acetate/hexane (1 :3) to give a pale yellow solid. A sample was dissolved in methanol/dichloromethane and hydrogen chloride in ether (1ml) was added. The solvent was evaporated and the residue triturated with ether and filtered off to give the title compound as a solid. LC/MS: Rt=3.67, [MH]+ 463.11 , 464.16.

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-Bromopyrazine-2,3-diamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; WO2006/114272; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 622392-04-5, name is 2-Bromo-5-iodopyrazine, 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 622392-04-5, Application In Synthesis of 2-Bromo-5-iodopyrazine

A 60% NaH dispersion in mineral oil (0.504 mg, 12.66 mmol, Aldrich) was added to a mixture of 2-cyclopropylethanol (1.0 g, 11.61 mmol, Lancaster) in THF (60 mL). The resulting mixture was stirred at ambient temperature under N2 for 20 min. Subsequently, 2-bromo-5-iodopyrazine (3.0 g, 10.55 mmol, Gateway Chemical) was added, and the resulting mixture was stirred at 65 C. under N2 for 3.5 hr. The mixture was then allowed to cool to ambient temperature overnight. THF was removed in vacuo, and the residue was diluted with ethyl acetate (150 mL) and deionized water (75 mL). The layers were separated, and the aqueous was back-extracted with ethyl acetate (50 mL). The combined ethyl acetate layers were then washed with 75 mL each of sat. NaHCO3(aq) and brine, dried over MgSO4, filtered, and concentrated to an oil in vacuo 3.0 g (~100%). It was observed that the alkoxide did not selectively displace the iodide versus bromide in this reaction. Thus, a mixture of the monoalkoxylated product resulted. This, however, did not matter for the next reaction

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; Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Boehm, Terri L.; Brown, David L.; Carroll, Jeffery N.; Chen, Yiyuan; Fobian, Yvette M.; Freskos, John N.; Gasiecki, Alan F.; Grapperhaus, Margaret L.; Heintz, Robert M.; Hockerman, Susan L.; Kassab, Darren J.; Khanna, Ish K.; Kolodziej, Stephen A.; Massa, Mark A.; McDonald, Joseph J.; Mischke, Brent V.; Mischke, Deborah A.; Mullins, Patrick B.; Nagy, Mark A.; Norton, Monica B.; Rico, Joseph G.; Schmidt, Michelle A.; Stehle, Nathan W.; Talley, John J.; Vernier, William F.; Villamil, Clara I.; Wang, Lijuan J.; Wynn, Thomas A.; US2005/9838; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem