Pyrazines

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

Preparation of intermediate DM A suspension of intermediate G (0.238 g, 1.01 mmol), 2-fluoropyrazine (0.123 mL, 1.52 mmol) and potassium carbonate (420 mg, 3.04 mmol) in DMSO (6.2 mL) was heated at 120 C using a single mode microwave (Biotage initiator60) with a power 25 output ranging from 0 to 400 W for 1 h [fixed hold time]. The reaction mixture was evaporated in Genevac and purified by preparative LC (irregular SiOH, 15-40 muiotaeta, 40 g, Merck, dry loading (silica), mobile phase gradient from DCM/MeOH from 100/0 to 90/10) to give 0.194 g of intermediate DM as a yellow solid (69%).

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

Reference:
Patent; JANSSEN SCIENCES IRELAND UC; GUILLEMONT, Jerome, Emile, Georges; MOTTE, Magali, Madeleine, Simone; RABOISSON, Pierre, Jean-Marie, Bernard; TAHRI, Abdellah; (194 pag.)WO2017/1660; (2017); 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 14508-49-7 as follows. Quality Control of 2-Chloropyrazine

In a sealed tube, 30 mL of dry toluene was degazed with Argon during 15 minutes, palladium acetate (114 mg, 0.17 mmol, 0.04 eq.) and racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (106 mg, 0.17 mmol, 0.04 eq.) were added and the mixture was degazed with Argon for 10 minutes. Then 2-chloropyrazine (500 mg, 4.37 mmol, 1.0 eq.), 4-amino-1-Boc-piperidine (1.05 g, 5.24 mmol, 1.2 eq.) and sodium tert-butoxide (587 mg, 6.11 mmol, 1.4 eq.) were added and the mixture was stirred at 70 C. overnight. The reaction was concentrated in vacuum. The resulting crude product was purified by flash chromatography on silica gel, eluting with 100% ethyl acetate to afford 106a (1.0 g, 82%).

According to the analysis of related databases, 14508-49-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Vetoquinol SA; US2009/221565; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 939412-86-9, 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. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

A stirred solution of trichloromethyl chloroformate (105 mmol, 12.68 mL) in tetrahydrofuran (100 mL) was cooled to 0 C and a solution of azetidine (88 mmol, 5 g) and N,N-diisopropylethylamine (193 mmol, 33.6 mL) in tetrahydrofuran (100 mL) was added slowly in 25 minutes. After stirring at 0 C for one hour the solids were removed by filtration and the filtrate was concentrated at 50 mbar (50C bath temperature). The residue was added to a solution of 2-aminomethyl-3-chloropyrazine hydrochloride (66.7 mmol, 12 g) and triethylamine (200 mmol, 27.9 mL) in dichloromethane (200 mL) and the reaction mixture was stirred for three hours. The solids were removed by filtration and the filtrate was concentrated in vacuo. Purification using column chromatography (silica gel; gradient dichloromethane / methanol 100:0 to 95:5) yielded 9.5 g of N-((3-chloropyrazin-2-yl)methyl)azetidine-1 -carboxamide. H NMR (CDCl3, 400 MHz): delta 2.30 (quintet, J = 9 Hz, 2H), 4.06 (t, J = 9 Hz, 4H), 4.66 (d, JJ = 2 Hz, 1 H), 8.45 (d, J = 2 Hz, 1 H).

The chemical industry reduces the impact on the environment during synthesis (3-Chloropyrazin-2-yl)methanamine hydrochloride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; N.V. ORGANON; MAN de,, Adrianus Petrus Antonius; REWINKEL,, Johannes Bernardus Maria; JANS,, Christiaan Gerardus Johannes Maria; RAAIJMAKERS,, Hans Cornelis Andreas; WIJKMANS,, Jacobus Cornelis Henricus Maria; WO2011/95556; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 59489-71-3, 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. 59489-71-3, name is 2-Amino-5-bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows.

To the solution of a 5-bromo-pyrazine-2-amine according to formula (ii) (10 g, 57.47 mmol) in 1,4-dioxane (100 ml) was added 4-methoxycarbonylphenylboronic acid (11.377 g, 63.21 mmol) followed by potassium phosphate tribasic (14.638 g, 68.96 mmol) and water 68.96 ml at RT. Reaction mixture was purged with N2 gas for lh. Bis(triphenylphosphine)palladium(II)chloride (2.823 g, 4.02 mmol) was added to the reaction mixture. The reaction mixture was heated to reflux for 16h, cooled to RT and concentrated under vacuum to remove dioxane. Solid was filtered, washed with water ( 20 ml X 3), dried and again washed with MeOH (10 ml X 4) and dried to afford compound a methyl carboxylate intermediate of formula (xiv) (12.035 g, 91.36%, 84% purity) as pale yellow solid.

The chemical industry reduces the impact on the environment during synthesis 2-Amino-5-bromopyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; UNIVERSITY OF CAPE TOWN; MMV MEDICINES FOR MALARIA VENTURE; YOUNIS, Yassir; CHIBALE, Kelly; WITTY, Michael, John; WATERSON, David; WO2013/121387; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 21279-62-9, These common heterocyclic compound, 21279-62-9, name is 3-Chloropyrazine-2-carboxamide, 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: The starting compound (1.27 mmol) was treated with 18 aliphatic amines, alicyclic amines or saturated heterocycles containing at least one nitrogen atom (2.54 mmol). Four reactions were completed by conventional heating methods. The conditions were 110 C, toluene as a solvent and pyridine (1.27 mmol) as a base. The reaction time was set to one hour. Then the reactions were completed using the microwave reactor with focused field and conditions used for syntheses were 140 C, 30 min,120 W, methanol used as a solvent and pyridine (1.27 mmol) as a base. They were set experimentally with respect to prior experience. The progress of reaction was monitored with TLC in system hexane/ethyl acetate (1:1). Then the mixture was separated by flash column chromatograph using gradient elution. Mobile phases were hexane and ethyl acetate again.

The synthetic route of 21279-62-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jandourek, Ondrej; Dolezal, Martin; Kunes, Jiri; Kubicek, Vladimir; Paterova, Pavla; Pesko, Matus; Buchta, Vladimir; Kralova, Katarina; Zitko, Jan; Molecules; vol. 19; 7; (2014); p. 9318 – 9338;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, 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. category: Pyrazines

Compound D1Sa (26 mg, 0.118 mmol), A6Rb (29 mg, 0.118 mmol) and DIPEA (46 mg, 0.357 mmol) were dissolved in 1,4-dioxane (2 mL), the reaction solution was heated to 130 C. and stirred for 16 hours in seal. The LCMS indicated the reaction was complete, the reaction mixture was concentrated in vacuo, the residue was purified via column chromatography (DCM/MeOH=100:1) to afford compound D4Rb (47 mg, yield 92%) as a pale yellow solid. MS m/z 429.2 [M+H]+, 430.2 [M+H]+.

The synthetic route of 313340-08-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hangzhou Innogate Pharma Co., Ltd.; ZHANG, Hancheng; LIU, Shifeng; YE, Xiangyang; (92 pag.)US2019/308993; (2019); 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. 3149-28-8, name is 2-Methoxypyrazine, A new synthetic method of this compound is introduced below., Computed Properties of C5H6N2O

CuSCN (100 mg, 0.82 mmol) was stirred in 500 muL neat 2-MeOPyz (5.18 mmol) under Ar for 3 d at ambient temp. A yellow solid was collected by filtration, washed with ethyl ether, and dried under vacuum (154 mg, 81%). IR (cm-1): 2123 (strong, sharp), 1587, 1529 (strong), 1471, 1438, 1398, 1311, 1284, 1195, 1145, 1060, 1014 (weak), 1004 (strong, sharp), 837, 759, 617. Anal. Calc. for C6H6Cu1N3O1S1: Cu, 27.42; C, 31.10; H, 2.61; N, 18.13. Found: Cu, 26.48; C, 31.12; H, 2.42; N, 17.95%. TGA calcd for CuSCN: 52.5%. Found: 53.9% (75-105 C).

The synthetic route of 3149-28-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Ayala, Gerardo; Tronic, Tristan A.; Pike, Robert D.; Polyhedron; vol. 115; (2016); p. 257 – 263;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 41270-66-0, The chemical industry reduces the impact on the environment during synthesis 41270-66-0, name is 5-Chloro-2,3-diphenylpyrazine, I believe this compound will play a more active role in future production and life.

A 2-butanone / water mixed solution (360 mL of 2-butanone and 22 mL of water) was placed,To the mixture was added sodium iodide 28g,Stir well after adding a starting material 22g, heated to reflux, smooth, add HI solution 8mL,Reflux overnight (due to the difference between raw material and product polarity, TLC can not track monitoring)The liquid phase was monitored to about 5% of the raw material (the reaction liquid was no longer reduced after 1 hour). The reaction mixture was filtered, the residue was washed with 4 mL of 2-butanone, the combined filtrates were swirled to remove the solvent,NaHSO3 0.7g aqueous solution 40mL, stir, then the solution was acidic, with stirring NaOH solid was added until the solution was strong alkaline, stirring to alkaline no longer change, filtration, the filter cake was recrystallized from methanol to give Compound 1 Dark yellow solid 17.8g,Yield 60.1%, purity 97.74%.

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-Chloro-2,3-diphenylpyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Nanjing Aide Kaiteng Bio-pharmaceutical Co., Ltd.; Wang Xuegen; He Lingyun; Wei Chao; Yu Yang; (6 pag.)CN106957269; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 16298-03-6, These common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, 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: Used for N-benzyl derivatives 1-8. The starting 3-aminopyrazine-2-carboxylic acid(Sigma-Aldrich, Schnelldorf, Germany; 2.2 g; 15.8 mmol) in methanol (250 mL) was cooled downto 0 C and concentrated H2SO4 (3.2 mL) was added. The reaction mixture was stirred for 48 h atrt. Subsequently the reaction mixture was poured into water (27 mL) and alkalized by NaHCO3(approx. 6.3 g) to pH = 7. The precipitate was filtered off and collected as white-brown solid toobtain methyl 3-aminopryzine-2-carboxylate [32]. Methyl 3-aminopyrazine-2-carboxylate (100 mg;0.65 mmol) in methanol (2 mL) along with substituted benzylamine (1.95 mmol; 3 equiv) and NH4Cl(10 mg; 0.19 mmol; 0.1 equiv) [33] were put into reaction tube used for microwave assisted synthesiswith a magnetic stirrer. Reaction was performed in a CEM Discover microwave reactor with a focusedfield in pressurized vials with the following settings: 130 C, 90 W and 40 min. The progress of thereaction was checked using TLC (Merck Silica 60 F254) developed by in hexane/ethyl-acetate 2:1 system.The reaction mixture was adsorbed to silica gel and purified by flash chromatography (Teledyne IscoInc.,) using silica (irregular, 40-63 m) as a stationary phase and gradient elution EtOAc in hexane0-100%, with respect to the expected lipophilicity of the product.

Statistics shows that Methyl 2-aminopyrazine-3-carboxylate is playing an increasingly important role. we look forward to future research findings about 16298-03-6.

Reference:
Article; Bouz, Ghada; Semelkova, Lucia; Jand?ourek, Ond?ej; Kone?na, Klara; Paterova, Pavla; Navratilova, Lucie; Kubi?ek, Vladimir; Kune?, Ji?i; Dole?al, Martin; Zitko, Jan; Molecules; vol. 24; 7; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 71257-38-0, 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. 71257-38-0 name is 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine, 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.

Example 1112,2-Dimethyl-1 -(7-(phenylethynyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)- yl)propan-1-one[00350] Pivaloyl chloride (3.27 g, 3.34 mL, 27.2 mmol) is added dropwise at 0 C to a solution of 1 ,2,3,4-tetrahydropyrrolo[1 ,2-a]pyrazine (3.01 g, 24.7 mmol) (WO2009/90055) and TEA (4.60 mL, 32.6 mmol) in DCM (40 mL). The resulting mixture is stirred at 0 C for 15 min and washed with an aqueous citric acid solution (10%). The organic phase is dried over MgSO and concentrated at reduced pressure. The obtained residue is purified by column chromatography (silica gel, DCM/acetone, 10:1 ) to give 1 -(3,4-dihydropyrrolo[1 ,2-a]pyrazin-2(1 H)-yl)-2,2-dimethylpropan-1 -one (3.10 g, 61 %) as a yellowish crystalline intermediate product.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; MERZ PHARMA GmbH & CO. KGaA; ZEMRIBO, Ronalds; FOTINS, Juris; ABEL, Ulrich; KUBAS, Holger; MEYER, Udo; WOLTER, Falko Ernst; HECHENBERGER, Mirko; WO2012/172093; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem