Month: August 2021

Application of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.

Example 1; (2S)-2- (fert-butoxycarbonyl) aminol-3-cLrcloheptylpropanoic acid building block; a) Methyl (2S)-2-amino-3-cycloheptylpropanoate; To a stirred solution of R-2,5-dihydro-3, 6-dimethoxy-2-isopropyl pyrazine (5 g, 27 mmol) in THF (80 mL) at-78 °C was added dropwise 2.5 M n-butyllithium in hexanes over 40 min, maintaining the temperature of the reaction mixture below-70 °C. To the reaction mixture was added dropwise a solution of iodomethylcycloheptane (Webb et al, J. Med. Chem. , 42,8 (1999), 1415-1421. ) (6.8 g, 28. 5 mmol) in THF (12 mL) over 50 min, maintaining the temperature of the reaction mixture below-70 °C. The reaction mixture was then stirred at 0 °C for another 75 min, acetic acid was added (2.45 mL) and stirring was continued for another 20 min. The reaction mixture was then diluted with ethyl acetate (200 mLI), washed with brine (2 x 50 mLI), dried (MgS04), filtered and concentrated in vacuo. Column chromatography of the residue using stepwise gradient elution (ethyl acetate in hexane 0-5percent) gave the pyrazine derivative as an oil (5.4 g, 68percent). A mixture of the pyrazine derivative (5.4 g, 18.5 mmol) in acetonitrile (55 mL), water (45 mL) and 1 M aqueous hydrochloric acid (45 mL) was stirred at room temperature for 2 h, then concentrated in vacuo to approximately half the volume. Aqueous NaHCO3 (1 M) was added until just alkaline, then the reaction was extracted with dichloromethane (3 x 50 mL). The extracts were dried (MgSO4), filtered and concentrated in vacuo onto silica. Column chromatography of the residue using stepwise gradient elution (ethyl acetate in hexane and triethylamine (0.5percent) 20-100percent) gave pure fractions of (8) which were concentrated in vacuo to a syrup (2.14 g, 58percent). Additional material could be obtained by repeated chromatography.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.

Reference:
Patent; MEDIVIR UK LTD; PEPTIMMUNE, INC; WO2005/82876; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 1458-18-0, The chemical industry reduces the impact on the environment during synthesis 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

Production Example 18-1 Methyl 3-amino-5,6-dimethylpyrazine-2-carboxylate A mixture of methyl 3-amino-5,6-dichloro-2-pyrazine carboxylate (200 mg, 0.90 mmol), X-Phos (170 mg, 0.36 mmol), tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.090 mmol), tetramethyltin (0.31 mL, 2.3 mmol), and N-methylpyrrolidinone (2 mL) was stirred at 130 C. for 2 hours under microwave irradiation. The reaction mixture was cooled to room temperature, water was added thereto at the same temperature, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate_heptane=3:2) to obtain the title compound (80 mg, 49% yield). 1H-NMR Spectrum (400 MHz, CDCl3) delta (ppm): 2.44 (s, 3H), 2.46 (s, 3H), 3.97 (s, 3H), 6.22 (br s, 2H).

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, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Eisai R&D Management Co., Lt.d; Tanaka, Keigo; Fukuyama, Takashi; Murai, Norio; Itano, Wataru; Hirota, Shinsuke; Iida, Daisuke; Azuma, Hiroshi; (32 pag.)US2016/168176; (2016); 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. 27398-39-6, name is 3-Chloropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Formula: C5H3ClN2O2

To a suspension of sodium hydride (278 mg, 6.95 mmol, 60percent in oil) in DMF (10 mL) was added 1H-pyrazole (279 mg, 4.11 mmol) at RT and the resulting mixture was stirred at room temperature for 30 mins. 3-Chloropyrazine-2-carboxylic acid (500 mg, 3.16 mmol) wasadded and the mixture heated to 60 °C for 2 h. After cooled to RT, water (20 mL) was added and the mixture extracted with 4.7percent MeOH in DCM (20 mL x 3). The combined organic layers were washed with brine, dried over Na2504, filtered, and concentrated in vacuo to give the title compound. LRMS m/z (M+H) 191.0 found, 191.0 required.

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 27398-39-6.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KIM, Ronald; KUDUK, Scott, D.; LIVERTON, Nigel; ZHUO, Gang; (97 pag.)WO2016/100157; (2016); 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. 951626-95-2, name is Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., name: Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

[00593] A 60 % dispersion of sodium hydride in mineral oil (0.395 g, 9.88 mmol) was added to a stirred solution of ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[l,5-a]pyrazine-2- carboxylate (1.88 g, 8.98 mmol) in DMF at 0 C. The mixture was stirred at this temperature for 1 h. Then, benzyl bromide was added and the mixture was stirred at room temperature for further 3 h. The mixture was diluted with water and extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo to yield ethyl 5 oenzyl- 4-oxo-4,5,6,7-tetrahydropyrazolo[l,5-a]pyrazine-2-carboxylate as a white oil (1.87 g, 66 % yield).

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; VANDERBILT UNIVERSITY; CONN, P., Jeffrey; LINDSLEY, Craig, W.; STAUFFER, Shaun, R.; BARTOLOME-NEBREDA, Jose Manuel; CONDE-CEIDE, Susana; MACDONALD, Gregor, James; TONG, Han Min; ALCAZAR-VACA, Manuel Jesus; ANDRES-GIL, Jose Ignacio; WO2013/192350; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486424-37-7, These common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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.

METHOD 11; Example 305; Synthesis of tert-butyl l-(3-(3-amino-6-bromopyrazine- 2-carboxamido)pyridin-4-yl)prperidin-3-ylcarbamate [0242] A solution containing 1 eq each of tert-butyl l-(3-aminopyridin-4- yl)piperidin-3-ylcarbamate, S-amino-beta-bromopyrazine-l-carboxylic acid, HOAT and EDC in DMF, at a concentration of 0.5 M, was stirred for 60 hours. The solution was diluted with EtOAc and was washed with H2O (4x), NaCl(sat.), was dried over MgSO4, was filtered and the volatiles were removed in vacuo. After purification by silica gel chromatography (EtOAc eluant), tert-butyl l-(3-(3-amino-6-bromopyrazine-2- carboxamido)pyridin-4-yl)piperidin-3-ylcarbamate was obtained (78%). LCMS (m/z): 492.2 (MH+); LC R, = 2.68 min.

The synthetic route of 486424-37-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS VACCINES AND DIAGNOSTICS, INC.; WO2008/106692; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

98-97-5, name is Pyrazine-2-carboxylic acid, 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. Formula: C5H4N2O2

Step A. Preparation o f Pyrazine-2-carbonyl chloride. A 500 ml three neck round bottomed flask equipped with a stir bar, thermocouple, heating mantle with digital temperature controller, condenser and nitrogen inlet/outlet was charged with 15 g (0.12 mol) of pyrazine carboxylic acid, 225 mL of toluene (Kf < 0.02wt%) and 26.4 ml (43 g, 0.36 mol) of thionyl chloride. The thin slurry was heated to 75 C and stirred overnight (10-16 hr). After cooling the reaction mixture to room temperature the solvent and excess thionyl chloride were removed in vacuo as follows: Reaction mixture was stripped under full vacuum at 60 C (bath temperature) to approximately 1/3 its original volume and then (175 ml) of fresh toluene was added. Concentration was continued, again stripping to 1/3 original volume followed by re-dilution with 225 ml of fresh toluene to provide the pyrazine acid chloride in a toluene solution. The synthetic route of 98-97-5 has been constantly updated, and we look forward to future research findings. Reference:
Patent; CEPHALON, INC.; ROEMMELE, Renee Caroline; WO2011/87822; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 19745-07-4, name is 2,5-Dichloropyrazine, 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 19745-07-4, Safety of 2,5-Dichloropyrazine

Intermediate C-5 2-chloro-3-((5-chloropyrazin-2-yl)thio)aniline A mixture of 3-amino-2-chlorobenzenethiol (724 mg, 3.69 mmol), 2,5- dichloropyrazine (500 mg, 3.36 mmol), and potassium carbonate (1.39 g, 10.07 mmol) in DMF/MeCN (1/1, 20 mL) was stirred for 4 h at 85 °C. After cooling to RT, the reaction mixture was filtrered through a pad of Celite followed by MeCN (10 mL) wash. The combined filtrates were concentrated under reduced pressure and the resulting residue was purified by silica chromatography (0 to 20percent gradient of EtO Ac/heptane) to give 2-chloro-3-((5-chloropyrazin-2- yl)thio)aniline (285 mg, 1.037 mmol). MS m/z. 272.1 (M+H)+.

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

Reference:
Patent; NOVARTIS AG; CHEN, Zhuoliang; FORTANET, Jorge Farcia; JOUK, Andriana; KARKI, Rajesh; LAMARCHE, Matthew J.; LIU, Gang; PALERMO, Mark G.; PEREZ, Lawrence Blas; SARVER, Patrick James; SHULTZ, Michael David; SENDZIK, Martin; TOURE, Bakary-Barry; YU, Bing; (173 pag.)WO2016/203406; (2016); 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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine

General procedure: A mixture of chloro compound (50 mg) and amine derivative (2 equiv.) in PEG 400 (2 mL) wasstirred at 120 C for 5 min. After completion the reaction was then cooled to room temperature. DCM and water were added and the phases were separated. The aqueous phase was extracted withDCM and the organic phase was dried and filtered. The removal of solvent gave the product as solid.

According to the analysis of related databases, 68774-77-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Campos, Joana F.; Loubidi, Mohammed; Scherrmann, Marie-Christine; Berteina-Raboin, Sabine; Molecules; vol. 23; 3; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4745-93-1, name is 5H-Pyrrolo[2,3-b]pyrazine, 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. Application In Synthesis of 5H-Pyrrolo[2,3-b]pyrazine

Step 8-Preparation of propane-1-sulfonic acid {2-fluoro-3-[hydroxy-(5H-pyrrolo[2,3-b]pyrazin-7-yl)-methyl]-phenyl}-amide (19); To propane-1-sulfonic acid (2-fluoro-3-formyl-phenyl)-amide (18, 50 mg, 0.42 mmol) in 0.8 mL of methanol, 5H-pyrrolo[2,3-b]pyrazine (3, 103 mg, 0.42 mmol) and potassium hydroxide (71 mg, 1.3 mmol) were added under an atmosphere of nitrogen. The reaction was stirred at room temperature for 48 hours, then poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 60% ethyl acetate in dichloromethane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a solid (19, 74 mg, 49%). MS (ESI) [M-H+]-=363.5.

The synthetic route of 4745-93-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ibrahim, Prabha N.; Spevak, Wayne; Cho, Hanna; US2009/306087; (2009); 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. 56423-63-3, name is 2-Bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 56423-63-3

General procedure: In a conical flask (50mL), a mixture of aryl halide (1 mmol), phenyl boronic acid (1.2 mmol),triethylamine (1 mmol), [Aemim]Br (1ml) and [Gmim]Cl-Pd (II) (0.1mol%, 5 mg)was added and stirred at 25OC for a period as indicated in Table 5(The reaction was monitored by HPLC and TLC). The resulting heterogeneousmixture was extracted with ethyl acetate or diethyl ether (3x 5 mL). Theorganic phase was separated and dried over anhydrous Na2SO4and evaporated. Evaporation of the solvent gave the crud product residue whichwas further purified by flash chromatography using n-hexane/EtOAc to give thedesired coupling product in 82-94% isolated yields.

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 56423-63-3.

Reference:
Article; Karthikeyan, Parasuraman; Vanitha, Arumugam; Radhika, Pachaiappan; Suresh, Kannan; Sugumaran, Arunachalam; Tetrahedron Letters; vol. 54; 52; (2013); p. 7193 – 7197;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem