Month: January 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 33332-25-1

Methyl 5-(chloropyrazine)-2-carboxylate (36 7) (2g, 0.0115mmol) was dissolved in 80mL of 87 DMSO. 88 Sodium azide (3g, 0.0463mmol) and 39 triphenylphosphene (4.6g, 0.1738mmol) were added and the mixture was refluxed at 120C for 4h. 20mL of 1N 89 HCl was added and the reaction was continued at 120C for 2h. The mixture was cooled and neutralized by using 90 aqueous NaHCO3 solution and 91 product was extracted in ethyl acetate, dried using Na2SO4. The ethyl acetate fraction was evaporated and washed with n-pentane to get 0.7g (yield 39.5%) yellow solid of compound 8. 1H NMR (400MHz, DMSO-d6) delta 8.53 (d, J=1.2Hz, 1H), 7.91 (d, J=1.2Hz, 1H), 7.39 (s, 2H), 3.79 (s, 3H). C6H7N3O2 [M]: 153.14; MS (ESI) m/z: [M-H]+: 152.05.

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; Trivedi, Prakruti; Adhikari, Nilanjan; Amin, Sk. Abdul; Jha, Tarun; Ghosh, Balaram; European Journal of Pharmaceutical Sciences; vol. 124; (2018); p. 165 – 181;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 68774-77-6, 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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

[0538] To a mixture of (R)-5-(2-(4-aminopiperidin-1-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one hydrochloride(60 mg, 0.16 mmol) and 5-cyano-2-fluoropyridine (20 mg, 0.16 mmol) in N-methylpyrolidinone (550 ml) was addedDIEA (57 ml, 0.33 mmol) in a microwave tube at room temperature. The tube was sealed and heated at 100C for 4 h.The mixture was cooled and partitioned between EtOAc/hexanes (2:1) and water. The aqueous layer was extractedwith EtOAc (2x). The combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated. Theresulting residue was purified by prep TLC (silica gel, 10% MeOH/DCM) to provide (R)-6-(1-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperidin-4-ylamino)nicotinonitrile. 1H-NMR (CDCl3, 500 MHz), delta 8.39 (m, 1H),7.82 (s, 2H), 7.60 (m, 1H), 6.41 (m, 1H), 5.29 (s, 2H), 4.92 (m, 1H), 3.23 (m, 1H), 2.96 (m, 1H), 2.39-2.46 (m, 4H), 2.18(s, 3H), 2.02 (m, 4H); LC-MS (IE, m/z): 393 [M + 1]+:_[0544] (R)-5-(2-(4-([1,2,4]Triazolo[4,3-a]pyrazin-8-ylamino)piperidin-1-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one was prepared in a similar fashion to that described for the synthesis of EXAMPLE 111 starting from (R)-5-(2-(4-aminopiperidin-1-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one hydrochloride and 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine. LC-MS (IE, mlz): 409 [M + 1]+.

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, 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Merck Sharp & Dohme Corp.; WALSH, Shawn; PASTERNAK, Alexander; CATO, Brian; FINKE, Paul, E.; FRIE, Jessica; FU, Qinghong; KIM, Dooseop; PIO, Barbara; SHAHRIPOUR, Aurash; SHI, Zhi-Cai; TANG, Haifeng; (136 pag.)EP2755656; (2016); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 109-08-0, name is 2-Methylpyrazine, molecular formula is C5H6N2, 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. name: 2-Methylpyrazine

General procedure: An oven-dried flask was purged with argon while hot, then allowed to cool down to room temperature under argon and charged with dry THF (2 mL/mmol of starting indole 3/6) and diisopropylamine (4.0 equiv). The solution was cooled to -78 ¡ãC in a dry ice/isopropanol bath and n-butyl lithium, 1.6 M solution in hexanes (4.0 equiv), was added to give a bright yellow solution. The mixture was stirred for 30 min below -60 ¡ãC whereupon a solution of picoline or another appropriate reagent with an ionizable methyl(ene) group (4.0 equiv) in THF (2 mL/mmol of starting indole 3 or 6) was added to give a yellow to red colored mixture. During a further 30 min, the bath temperature was allowed to rise to approx. 0 ¡ãC during which time the reaction mixture became a yellow to red suspension. The temperature was then kept at 0 ¡ãC (using an ice/water bath) for an additional 30 min. At this point, a solution of the indole-2-carbonyl compound 3/6 (1.0 equiv) in THF (4 mL/mmol) was added dropwise over the flask wall. The reaction mixture darkened (dark purple to dark brown color in most cases) and was then allowed to attain room temperature overnight. At 18 h (unless otherwise stated) after the addition of the indole component, the reaction was quenched with saturated aqueous ammonium chloride solution (10 mL/mmol of starting compound 3/6) and stirred for several minutes. Upon partition between ethyl acetate and water, the aqueous phase was extracted twice with dichloromethane and the combined organic layers were dried over MgSO4. The title products were purified by chromatography (the products typically eluted with 70-80percent of ethyl acetate). The products were then precipitated by concentration of the pooled column fractions combined with the addition of cyclohexane. The precipitates formed were filtered off, washed twice with cyclohexane and dried at 40 ¡ãC in vacuo to yield analytically pure samples. The following compounds were prepared in this way:

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109-08-0, its application will become more common.

Reference:
Article; Dolusic, Eduard; Larrieu, Pierre; Blanc, Sebastien; Sapunaric, Frederic; Norberg, Bernadette; Moineaux, Laurence; Colette, Delphine; Stroobant, Vincent; Pilotte, Luc; Colau, Didier; Ferain, Thierry; Fraser, Graeme; Galeni, Moreno; Frre, Jean-Marie; Masereel, Bernard; Van Den Eynde, Benoit; Wouters, Johan; Frederick, Raphael; Bioorganic and Medicinal Chemistry; vol. 19; 4; (2011); p. 1550 – 1561;,
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 36070-75-4 as follows. Quality Control of 5-Chloropyrazine-2-carbonitrile

To a microwave vial 5-chloropyrazine-2-carbonitrile (74.1 mg, 0.531 mmol), rac-(2S,3R,4R)-1-acetyl-4-amino-2-cyclopropyl-N,3-dimethyl- 1,2 ,3,4-tetrahydroqu inoline-6-carboxamide (for preparation seeIntermediate 200, 80 mg, 0.265 mmol), and DIPEA (0.139 mL, 0.796 mmol) were added and thereaction irradiated at 200 C in a microwave for 30 mins. The reaction was purified directly usingMDAP (Formic) to give a beige solid. This solid was eluted through a NH2 SPE (5 g) with MeOH, theeluent was concentrated to the product (63 mg, 0.156 mmol, 58.7%) as a beige solid.LCMS (2 mm Formic): Rt = 0.78 mi [MH] = 405.

According to the analysis of related databases, 36070-75-4, the application of this compound in the production field has become more and more popular.

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: 5521-55-1, name is 5-Methylpyrazine-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 5521-55-1, category: Pyrazines

In methanol (15 ml), 5-methylpyrazine-2-carboxylic acid (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (1.25 g) was dissolved. Then, the solution was added with WSCI hydrochloride (2.59 g) and N,N-dimethylaminopyridine (1.65 g) in this order, followed by stirring at room temperature for 3 hours. The reaction solution was added with water and then extracted with chloroform. The organic layer was washed with saturated saline solution and then dried with anhydrous sodium sulfate. The solvent was distilled off and the resulting crude product was then purified through silica gel column chromatography (chloroform/methanol). The purified product was dissolved in ethanol (15 ml) and THF (8 ml) and added with calcium chloride (1.11 g). After that, the reaction solution was cooled to 0C and then gradually added with sodium borohydride (757 mg), followed by stirring at room temperature for 19 hours. The reaction solution was added with a 1 mol/l citric acid solution (40 ml), followed by extraction with ethyl acetate. The organic layer was washed with saturated saline solution and then dried with anhydrous sodium sulfate, followed by distilling the solvent off. The residue was dissolved in chloroform (10 ml) and then added with manganese dioxide (chemically processed product) (2.2 g), followed by stirring at room temperature for 1 hour. After completion of the reaction, the catalyst was filtrated out through Celite and the solvent was then distilled off. The crude product obtained was purified through silica gel column chromatography (chloroform/methanol), thereby obtaining the subject compound (35.9 mg) as a colorless oily substance.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Methylpyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; Kureha Chemical Industry Co., Ltd.; EP1550657; (2005); 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. 426829-61-0, name is N-Benzyl-6-chloropyrazin-2-amine, A new synthetic method of this compound is introduced below., Computed Properties of C11H10ClN3

Step 2: N-Benzyl-6-(1-Piperazinyl)-2-Pyrazinamine. A mixture of the product from step 1 above (1.25 g, 5.7 mmol), piperazine (1.0 g, 11.6 mmol), and K2CO3 (1.0 g, 7.3 mmol) in dioxane (3 mL) was heated at 160 C. for 11 h in a sealed pyrex flask. The reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The red-brownish residue was dissolved in a small volume of CHCl3/MeOH (9:1) and purified by silica gel chromatography (15 *4 cm) using CHCl3/MeOH (95:5, followed by 9:1) as eluent. The free base was obtained as a brownish solid (0.9 g, 3.33 mol) that was redissolved in methanol (10 mL). Maleic acid (0.45 g, 3.83 mmol) in methanol (5 mL) was added and the salt was precipitated out by addition of ether. The salt was recrystallized from MeOH-ether and finally converted back to the free base by alkalinization (10% aqueous Na2CO3) and extraction with ether (5*60 mL). The combined ether layers were dried (K2CO3), filtered and concentrated. This furnished 0.36 g (23%) of the title compound as a light yellow powder. HRMS m/z calcd for C15H19N5(M)+269.1640, found 269.1641. Anal. (C15H19N5) C, H, N.

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; Nilsson, Bjorn M.; US2002/147200; (2002); 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. 4774-14-5, name is 2,6-Dichloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., Formula: C4H2Cl2N2

General procedure: To a solution of N,N-dimethylethylenediamine (0.192 mL, 1.75 mmol) in DMF (5mL) was added K2CO3 (0.278 g, 2.01 mmol). After stirring for 30 min at RT, 2,6-dichloropyrazine (0.200 g, 1.34 mmol) was added to the reaction mixture. After stirring overnight at RT, solvent was removed under reduced pressure.

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:
Article; More, Kunal N.; Jang, Hyo Weon; Hong, Victor S.; Lee, Jinho; Bioorganic and Medicinal Chemistry Letters; vol. 24; 11; (2014); p. 2424 – 2428;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 63286-28-2, 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. 63286-28-2 name is 2-Chloro-3-hydrazinylpyrazine, 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.

Intermediate B-1 (15.0 g; 104 mmol) is suspended in toluene (135 mL) at ambient temperature. Acetic anhydride (11.1 g; 109 mmol) dissolved in 7.5 mL toluene is slowly added to the suspension. The reaction mixture is stirred at ambient temperature for 2.5 h. The product is isolated by filtration. Yield: 99 % (19.2 g, 103 mmol) ESI-MS: (M+H)+ = 187/189

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

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; TONTSCH-GRUNT, Ulrike; BAUM, Anke; RUDOLPH, Dorothea Ingrid; (85 pag.)WO2019/145410; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 56423-63-3, name is 2-Bromopyrazine, molecular formula is C4H3BrN2, 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. COA of Formula: C4H3BrN2

Dissolve YC042 (100 mg, 0.4 mmol) and 2-bromopyrazine (127 mg, 0.8 mmol) in DME.Add 1.6 mL of 2M sodium carbonate aqueous solution, and then introduce nitrogen after evacuation. Add catalyst Pd (dppf) 2Cl2-CH2Cl2 (17mg). After evacuation again, introduce nitrogen, reflux at 95 C overnight, dilute with water, extract with ethyl acetate, organic The phases were dried over anhydrous sodium sulfate and spin-dried and purified on a normal phase silica gel column.YC075 (75.8mg)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 56423-63-3, its application will become more common.

Reference:
Patent; Chinese Academy Of Sciences Shanghai Pharmaceutical Institute; Zhao Yujun; Li Jia; Wang Zengtao; Zhang Shiyan; Zang Yi; Wang Peipei; Sun Dandan; Zhang Hanyan; (155 pag.)CN110818683; (2020); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

173290-17-0, name is Methyl 3-iodopyrazine-2-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. HPLC of Formula: C6H5IN2O2

Example 5 Preparation of Methyl 3-trifluoromethyl-pyrazine-2-carboxylate (8) To methyl 3-iodopyrazine-2-carboxylate (7) (10 g, 37.88 mmol) in DMF (Volume: 300 mL) was added methyl chlorodifluoroacetate (27 g, 0.189 mol), potassium fluoride (13.2 g, 0.227 mol), and copper chloride (22.47 g., 0.227 mol). The reaction was heated at 120 C. for 12 h. The reaction mixture was poured into ethyl ether (1000 ml) and washed with brine (3*300 ml), dried over MgSO4 before the solvent was removed. The residue was loaded onto a silica column and was eluted using ethyl acetate/hexanes gradient to afford the title compound (3.19 g, 41%) as an amber oil: 1H NMR (400 MHz, CDCl3) delta 8.85 (d, J=5.4 Hz, 1H), 8.82 (d, J=5.4 Hz, 1H), 4.05 (s, 3H); EIMS m/z 206.

The synthetic route of 173290-17-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DOW AGROSCIENCES LLC; US2011/301178; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem