Month: April 2021

Adding a certain compound to certain chemical reactions, such as: 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, 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 33332-25-1, SDS of cas: 33332-25-1

4-((7-azaspiro[3.4]nonan-2-oxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole (100 mg, 0.24 mmol) is dissolved in DMF (5 mL), followed by adding methyl 5-chloropyrazine -2-carboxylate (45 mg, 0.26 mmol) and potassium carbonate (81 mg, 0.59 mmol), and the mixture is heated to 80 C and continues to react for 2 hr. Then the reaction mixture is cooled down to room temperature, poured into water (20 mL), and extracted with ethyl acetate (15 mL * 2) and the organic layer is washed with saturated salt solution (20 mL * 2), then dried with anhydrous Na2SO4, filtered, rotated to dryness and purified by column chromatography (PE : EA = 1.5 : 1), so as to obtain a brown oily matter of 100 mg, that is methyl 5-(2-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)-6-azaspiro[3.4]octan-6-yl)pyr azine-2-carboxylate with a yield of 81%. Spectrum is: 1H NMR (400 MHz, CDCl3) delta: 8.81(m, 1H), 7.86(m, 1H), 7.46-7.44(m, 2H), 7.39-7.34(m, 1H), 4.21(s, 2H), 3.97(m, 4H), 3.58-3.44(m, 4H), 2.16(m, 3H), 1.98(m, 2H), 1.83(m, 2H), 1.29(m, 2H), 1.15(m, 2H).

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; Guangzhou Henovcom Bioscience Co. Ltd.; ZHANG, Jiancun; ZOU, Qingan; CHEN, Yanwei; (64 pag.)EP3401315; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, 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. Recommanded Product: 75907-74-3

Were added 2-hydroxymethyl-3,5,6-trimethyl pyrazine in 250mL three-necked flask (9.5g, 62.5mmol), MnO2(16.2g, 187.5mmol), ethanol 100mL, refluxed for 12h, TLC (petroleum ether – ethyl acetate 2: 1) detecting the reaction is substantially complete, cooled, filtered, recovering ethanol under reduced pressure to give a yellow solid by silica gel column chromatography (petroleum ether – ethyl acetate 4: 1) to give 8.8 g of a pale yellow solid, yield 93.9%.

The synthetic route of 75907-74-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Anhui University of Chinese Medicine; Hefei Medical Engineering Pharmaceutical Co., Ltd.; Hefei Enruite Pharmaceutical Co., Ltd.; Li Jiaming; He Guangwei; Zhang Yang; Huang Weijun; Zhang Yanchun; Liu Weizhong; Zuo Jian; Liu Huicai; Zhu Panhu; Wang Yujun; (14 pag.)CN106518791; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 13301-04-7, A common heterocyclic compound, 13301-04-7, name is Methyl 3,6-dibromopyrazine-2-carboxylate, molecular formula is C6H4Br2N2O2, 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.

To a dimethylformamide (15 ml) solution of 3,6-dibromopyrazine-2-carboxylic acid methyl ester (see Patent Document: BE662507)(780 mg, 2.64 mmol), potassium carbonate (364 mg, 2.64 mmol)) and 4-fluorothiophenol (0.253 ml, 2.37 mmol) were sequentially added at room temperature and the mixture was stirred at room temperature for one hour. The reaction solution was charged with water, extracted with chloroform and then dried (over anhydrous magnesium sulfate), filtered and concentrated to obtain a residue, which was purified by silica gel column chromatography [developing eluent: chloroform hexane = 1:2 to 10:0] and purified by recycle preparative HPLC (LC-908 type, Japan Analytical Industry Co. , Ltd.) [developing eluent: chloroform] to obtain a mixture of 6-bromo-3-[(4-fluorophenyl)sulfanyl]pyrazine-2-carboxylic acid methyl ester and 3-bromo-6-[(4-fluorophenyl)sulfanyl]pyrazine-2-carboxylic acid methyl ester (940 mg) in the form of a light yellow solid substance.

The synthetic route of 13301-04-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Taisho Pharmaceutical Co. Ltd.; Nissan Chemical Industries, Ltd.; EP2157090; (2010); 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 4774-14-5 as follows. category: Pyrazines

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXIII) (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 (LXIV) (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 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 (LXV) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C12H17CIN4O2 m/z 285.1 (M+H).

According to the analysis of related databases, 4774-14-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil, Kumar; WALLACE, David, Mark; CAO, Jianguo; CHIRUTA, Chandramouli; HOOD, John; (279 pag.)WO2017/23973; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 944709-42-6, name is 6,8-Dibromo-[1,2,4]triazolo[1,5-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 944709-42-6, Recommanded Product: 944709-42-6

Into a flask, under an inert atmosphere of nitrogen, was placed 1,1,1-trifluoro-4-iodobutane (6.7 g, 28 mmol), zinc metal (3.7 g, 56 mmol) and DMA (10 mL). This was followed by the dropwise addition of a solution of iodine (0.33 g, 1.3 mmol) in DMA (0.5 mL). The resulting mixture was stirred for 3 h at 80¡ãC. The reaction was cooled and directly used in the next step. Into a flask, under an inert atmosphere of nitrogen, was placed 6,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (6.0 g, 22 mmol), Pd(PPh3)2Cl2 (0.91 g, 1.3 mmol) and THF (80 mL). The resulting mixture was allowed to stir for 1 h at RT. The intermediate from Step A (11 mL, 28 mmol) was added and the resulting solution was stirred for 16 h at RT. The reaction was quenched by the addition of sat. aq. NH4Cl. The resulting solution was extracted with EtOAc (3X) and the organic layers were combined, washed with brine, dried over anhydr. Na2SO4, and filtered. The filtrate was conc. in vacuo to dryness. The residue purified by silica gel chromatography with EtOAc:petroleum ether (0-20percent) to afford the title compound.

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, 6,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BERGER, Raphaelle; DONG, Guizhen; RAGHAVAN, Subharekha; YANG, Zhiqiang; (179 pag.)WO2017/200857; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 63744-22-9, name is 6,8-Dibromoimidazo[1,2-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 63744-22-9, category: Pyrazines

[0310] 6-Bromo-N-(4-(4-(oxetan-3-ylmethyl)piperazin-1-yl)phenyl)imidazo[1,2- a]pyrazin-8-amine XXXI: To a seal tube equipped with a stirring bar, 4-(4-(oxetan-3- ylmefhyl)piperazin-1-yl)aniline XXX ( 1.19 g, 4.81 mmol), 6,8-dibromoimidazo[1,2- a]pyrazine (1.33 g, 4.81 mmol), isopropanol (24.1 mL), and diisopropylethylamine (1.37 g, 10.58 mmol) were added, and the reaction mixture was heated at 100 C overnight. Most solvents were removed in vacuo and DCM (200 mL) was added to the mixture. The solution was washed with H2O (20 mL x 2), brine (20 mL x 1), dried over Na2S04, filtered and solvents were removed in vacuo. The resulting residue was passed through a silica gel column (MeOH: DCM = 5: 95) and light red solids were obtained as the desired compound XXXI, 0.692 g (yield 32.4 %).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6,8-Dibromoimidazo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; GILEAD SCIENCES, INC.; BLOMGREN, Peter, A.; CLARKE, Astrid; CURRIE, Kevin, S.; DI PAOLO, Julie; KROPF, Jeffrey, E.; LEE, Seung, H.; LO, Jennifer, R.; MITCHELL, Scott, A.; SCHMITT, Aaron, C.; SWAMINATHAN, Sundaramoorthi; XIONG, Jin-Ming; XU, Jianjun; ZHAO, Zhongdong; (169 pag.)WO2016/10809; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, 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. name: Methyl 2-aminopyrazine-3-carboxylate

Preparation of 3-aminopyrazine-2-carbaldehyde EPO Mpsithyl-3-aminopyrazine-2-carboxylate (11g) was dissolved in THF and cooled to – 780C. Diisobutylaluminum hydride (1 M in hexanes, 25OmL) was added, and the reaction stirred at -78¡ãC for 4 hours. The reaction was then warmed to 00C for one hour before being quenched slowly by addition of 1 M hydrochloric acid. Ethyl acetate was added and the layers separated. The organic layer was dried over magnesium sulfate, filtered and concentrated. The residue was triturated in hexanes to afford title compound (3.Og, 34percent).1H NMR (400 MHz, DMSO-D6) delta ppm 7.73 (br, 2H), 8.07 (d, J=2.25 Hz, 1 H), 8.36 (d, J=2.11 Hz, 1 H), 9.95 (s, 1 H).

The synthetic route of 16298-03-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2006/63167; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

2423-65-6, name is Pyrazine 1-oxide, 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. HPLC of Formula: C4H4N2O

Preparation 28 2-Amino-6-cyanopyrazine This intermediate was prepared via a stepwise procedure. A mixture of 21 g. of pyrazine-2-carboxamide, 85 ml. of glacial acetic acid, and 75 ml. of 30 percent hydrogen peroxide was heated at about 55¡ã C. for about 35 hours. The reaction product mixture was cooled and filtered. The solid which was collected was extracted with n-butanol and the extracts discarded. The solid which was insoluble in n-butanol was recrystallized from hot water to yield a white solid having a melting point of about 302¡ã-305¡ã C. The solid was identified by elemental analyses as pyrazine-2-carboxamide 4-oxide. To a mixture of 4 g. of the pyrazine oxide (prepared above) in 40 ml. of dimethylformamide cooled in an ice bath, there was quickly added 12 ml. of phosphorus oxychloride. The reaction mixture was poured into water and the aqueous mixture extracted with ethyl acetate, and the extracts saved. Additional water was added to the aqueous layer and the aqueous mixture extracted with hexane-ether. The ethyl acetate and hexane-ether extracts were combined and concentrated in vacuo to leave a residue. The residue was identified by elemental analyses and IR spectrum as 2-chloro-6-cyanopyrazine, and was used without further purification in the next step. A mixture of 1 g. of the above chlorocyanopyrazine and 25 ml. of dimethyl sulfoxide was prepared and anhydrous ammonia was bubbled thereinto. The reaction mixture was stirred overnight and then poured into water. The aqueous mixture was extracted with ethyl acetate, and the extracts dried. The drying agent was filtered off and the solvent removed in vacuo to leave a solid which was identified by its IR spectrum as 2-amino-6-cyanopyrazine. It was used as is without further purification in the preparation of final products of the invention.

The synthetic route of 2423-65-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Eli Lilly and Company; US4293552; (1981); 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. 59303-10-5, name is 2-Chloro-5-methylpyrazine, A new synthetic method of this compound is introduced below., Product Details of 59303-10-5

The 2-chloro-5-methylpyrazine (0.053 mL, 0.613 mmol), rac-l -((2S,3R,4R)-4-amino-2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)-3-methyl-3,4-dihyd roquinolin- I (2H)-yl)ethanone (for a preparation seeIntermediate 78, 100 mg, 0.306 mmol), Pd2(dba)3 (42.1 mg, 0.046 mmol), sodium tert-butoxide (88mg, 0.919 mmol) and DavePhos (12.06 mg, 0.031 mmol) were suspended in 1,4-dioxane (10 mL)and allowed to stir at 100 C for 3 h. The reaction was allowed to cool and was partitioned between water and EtOAc, the organic layer was washed with brine, dried using a hydrophobic frit and concentrated to a gum. This gum was purified by column chromatography on silica gel eluting with 0- 50% EtOAc:cyclohexane and then 0-10% MeOH:DCM, to give a crude gum. This gum was furtherpurified using a MDAP (Formic) to give a white solid, this solid was eluted through a NH2 SPE (2 g) with MeOH the eluent was concentrated and dried to give the product (46 mg, 0.110 mmol, 35.9%) as an off-white solid. LCMS (2 mm Formic): Rt = 0.93 mi [MH] = 419.

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; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AMANS, Dominique; ATKINSON, Stephen John; HARRISON, Lee Andrew; HIRST, David Jonathan; LAW, Robert Peter; LINDON, Matthew; PRESTON, Alexander; SEAL, Jonathan Thomas; WELLAWAY, Christopher Roland; WO2014/140076; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 55557-52-3, name is 3-Chloropyrazine-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 55557-52-3, Recommanded Product: 55557-52-3

EXAMPLE 8.1 (+-)-3-[(6R,8aS)-6-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]pyrazin e-2-carbonitrile A mixture of (+-)-(6R,8aS)-octahydropyrrolo[1,2-a]pyrazin-6-ylmethanol (1.05 g, crude), 3-chloropyrazine-2-carbonitrile (860 mg, 6.2 mmol), Et3N (1.5 mL) and THF (10 mL) was stirred at 80 C. overnight. After concentration, the crude product was purified on a silica gel column to afford pure product (1.03 g, 77%). 1H NMR (300 MHz, CDCl3): delta (ppm) 1.45 (m, 1H), 1.85 (m, 3H), 2.41 (m, 3H), 2.63 (m, 1H), 2.92 (dd, 1H), 3.18 (m, 2H), 3.53 (t, 1H), 3.79 (dd, 1H), 4.61 (m, 2H), 8.03 (s, 1H), 8.27 (s, 1H).

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

Reference:
Patent; AstraZeneca AB; NPS PHARMACEUTICALS; US2007/37817; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem