Pyrazines

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. 313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 3,5-Dichloro-6-ethylpyrazine-2-carboxamide

Compound 1-4 (2.2 g, 10 mmol) was weighed into a single-necked flask, and 15 ml of a 2N hydrochloric acid methanol solution was added, and the reaction was refluxed for 12 h. After the reaction is completed, the reaction solution is concentrated under reduced pressure and purified by column chromatography. A colorless liquid product 3-1, 1.9 g was obtained.

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

Reference:
Patent; Chinese Academy Of Sciences Shanghai Pharmaceutical Institute; Zhang Ao; Geng Meiyu; Ye Jiqing; Ai Jing; Song Zilan; (29 pag.)CN109384774; (2019); 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. 13301-04-7, name is Methyl 3,6-dibromopyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 13301-04-7

To a dimethylformamide (300 ml) solution of 3,6-dibromopyrazine-2-carboxylic acid methyl ester (7.47 g, 25.2 mmol), potassium carbonate (3.48 g, 25.2 mmol) and 4-fluorothiophenol (2.42 ml, 22.7 mmol) were sequentially added at room temperature and the mixture was stirred at room temperature for 30 minutes. The reaction solution was charged with water, extracted with ethyl acetate and then washed (with water and brine in this order). The water phases were combined and re-extracted with chloroform. The organic phases were combined, dried (over anhydrous magnesium sulfate), filtered and concentrated to obtain a residue, which was purified by silica gel column chromatography [developing eluent: hexane: ethyl acetate = 25:1 to 10:1] to obtain a mixture (9.29 g) of 6-bromo-3-[(4-fluorophenyl)sulfanyl]pyrazine-2-carboxylic acid methyl ester, 3-bromo-6-1(4-fluorophenyl)sulfanyl]pyrazine-2-carboxylic acid methyl ester and 3,6-bis[(4-fluorophenyl)sulfanyl]pyrazine-2-carboxylic acid methyl ester.

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; Taisho Pharmaceutical Co. Ltd.; Nissan Chemical Industries, Ltd.; EP2157090; (2010); 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. Recommanded Product: 2-Bromopyrazine

Step A: 2-(2-Chlorophenyl)pyrazine (2508) 2-Bromopyrazine (100 mg, 0.630 mmol) and ((2-chlorophenyl)boronic acid (103 mg, 0.660 mmol) were added to a 5 mL sealable vial equipped with a stir-bar. A solution consisting of 1,4-dioxane (3 mL) and Na2CO3 (1.6 mL, 2 M) was added and the mixture sparged with argon for 10 minutes before adding Pd(ddp)Cl2.CH2Cl2 (23 mg, 0.031 mmol) and heating at 80 Celsius for 15 hours. The reaction was then cooled to rt, diluted with 5 mL of ethyl acetate and 5 mL of water, and the mixture extracted with ethyl acetate (3×20 mL). The combined organic extracts were then dried with sodium sulfate and concentrated to dryness. The resultant residue was subjected to FCC to provide the title compound. 1H NMR (500 MHz, CDCl3) delta 8.98-8.96 (d, J=1.6, 1H), 8.70-8.68 (dd, J=2.5, 1.6, 1H), 8.58-8.56 (d, J=2.6, 1H), 7.66-7.58 (m, 1H), 7.54-7.50 (m, 1H), 7.43-7.39 (m, 2H).

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; JANSSEN PHARMACEUTICA NV; Bacani, Genesis M.; Eccles, Wendy; Fitzgerald, Anne E.; Goldberg, Steven D.; Hack, Michael D.; Hawryluk, Natalie A.; Jones, William M.; Keith, John M.; Krawczuk, Paul; Lebsack, Alec D.; Lee-Dutra, Alice; Liu, Jing; McClure, Kelly J.; Meduna, Steven P.; Pippel, Daniel J.; Rosen, Mark D.; Sales, Zachary S.; US2015/259357; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4774-14-5, 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. 4774-14-5 name is 2,6-Dichloropyrazine, 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.

Compound 5-5 was prepared using 3,5-dichloro-2-methylpyrazine and l-boc-4- hydroxypiperidine in Step 3.; 3 ,5-dichloro-2-methylpyrazine; To a solution of n-butyl lithium (1.6M in hexanes; 29 mL, 47 mmol) in tetrahydrofuran (200 mL) at -30C was added 2,2,6,6-tetramethylpiperidine (8.6 mL, 50 mmol). This solution was allowed to warm to 00C over 20 minutes then cooled to -78C. To this solution was added a solution of 2,6-dichloropyrazine (5 g, 34 mmol) in tetrahydrofuran (200 mL) dropwise via cannula. After 30 minutes, iodomethane (21 mL, 340 mmoL) was added. After 1 h, the reaction mixture was quenched with a mixture of EtOH (25 mL), THF (25 mL) and IN aqueous HCl (5 mL). The reaction mixture was allowed to warm to room temperature then concentrated to a crude oil. The crude oil was partitioned between water (500 mL) and CH2Cl2 (500 mL). The organic layer was washed with brine (250 mL). The first aqueous layer was back-extracted with CH2Cl2 (500 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford 3,5-dichloro-2-methylpyrazine as a yellow oil. LRMS (ESI) calculated for C5H4Cl2N2 [M+H]+, 163.0; found 163.1.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,6-Dichloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; MERCK & CO., INC.; WO2009/54941; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6705-33-5, 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 6705-33-5 as follows.

Example 4; 4-Bromo-1-(2,2-dimethylpropyl)-5-(pyrazin-2-ylmethoxy)-1H-1,2,3-benzotriazole (Example 4-1) To a suspension of 4-bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-ol (Example 1-2) (1.5 g, 5.28 mmol, 1.0 equiv.), 2-pyrazinylmethanol (13) (0.581 g, 5.28 mmol, 1.0 equiv.) and polymer-supported triphenylphosphine (2.2 mmol/g, 5.75 g, 21.91 mmol, 2.5 equiv.) in THF (37.7 ml) and DCM (37.7 ml) was slowly added di-tert-butyl azodicarboxylate (2.431 g, 10.56 mmol, 2.0 equiv.). After stirring at room temperature for 1 hr, the reaction mixture was passed through a filter. The residue was washed with DCM and THF. The filtrate was concentrated to dryness to give a solid, which was taken up in DCM (12 mL) and treated with TFA (6 mL). The mixture was stirred at room temperature until LCMS showed only the desired product. The reaction mixture was neutralized to pH=7 with saturated aqueous NaHCO3, and then extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (EtOAc/Hexane gradient from 0 to 100%) to obtain product Example 4-1. 1H NMR delta (CDCl3): 9.06 (s, 1H), 8.59-8.57 (m, 2H), 7.42 (d, 1H, J=9.5 Hz), 7.31 (d, 1H, J=9.0 Hz), 5.38 (s, 2H), 4.38 (s, 2H), 1.04 (s, 9H) ppm. LRMS m/z (M+H) 376.1 and 378.1 (intensity ratio 1:1) found, 376.1 and 378.1 required.

According to the analysis of related databases, 6705-33-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Beshore, Douglas C.; Dudkin, Vadim; Garbaccio, Robert M.; Johnson, Adam W.; Kuduk, Scott D.; Skudlarek, Jason W.; Wang, Cheng; Fraley, Mark E.; US2012/135977; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 33332-29-5, 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 33332-29-5 as follows.

General procedure: Method B is a modification of Method A and was performed under nitrogen atmosphere andwith extended work-up. Substituted benzoyl chloride (1.5 mmol, 1.2 equiv) was placed into the askunder nitrogen, diluted with dry DCM (5 mL) and dry pyridine (400 mg, 5 mmol, 4 equiv) was added.The mixture was mixed for 5 min under nitrogen. Then, 5-chloropyrazin-2-amine (162 mg, 1.25 mmol,1 equiv) dissolved in DCM (10 mL) was added dropwise over 10 min under nitrogen ow. The askwas closed by septum and stirred for additional 6 h. After reaction, the mixture was diluted with DCMto the final volume of 40 mL and washed with water (1 30 mL), 5% (m/m) aqueous NaHCO3 solution(1 30 mL), and brine (1 30 mL). The organic layer was dried over anhydrous Na2SO4 and adsorbedon silica (4 g) by evaporating the solvents under reduced pressure. Automated flash chromatographywas run using same conditions as described in Method A. If needed, the products were recrystallizedfrom hot EtOH (crystallization initiated by cooling and dropwise addition of cold water).

According to the analysis of related databases, 33332-29-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Zitko, Jan; Mindlova, Al?b?ta; Vala?ek, Ond?ej; Jand’ourek, Ond?ej; Paterova, Pavla; Janou?ek, Ji?i; Kone?na, Klara; Dole?al, Martin; Molecules; vol. 23; 9; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 13134-31-1, name is 2,3-Diaminopyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Product Details of 13134-31-1

EXAMPLE 2 2-(2-Methoxy-4-benzyloxy-phenyl)-imidazo[4,5-b]pyrazine A mixture of 2.2 g of 2,3-diaminopyrazine and 5.16 g of 2-methoxy-4-benzyloxy-benzoic acid was finely triturated in a mortar and then suspended in 80 ml of phosphorus oxychloride. The suspension was refluxed for 1.5 hours while stirring. After cooling, the reaction mixture was mixed with ice water. The solution thus obtained was neutralized with ammonia and extracted with ethyl acetate. The ethyl acetate phases were evaporated, and the residue was triturated with acetone, whereupon the reaction product was left behind in pure form. A second fraction was obtained by evaporating the acetone phase and purifying the residue on silica gel (eluant: methylene chloride/ethanol =100:0 to 100:4). Yield: 3.2 g (48% of theory). M.p. 178-180 C.

The synthetic route of 13134-31-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dr. Karl Thomae GmbH; US4656171; (1987); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 113305-94-5, 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. 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 26 (E)-5-((4-Amino-8-(4-(2-cyanovinyl)-2,6-dimethylphenyI)-6-fluoroquinazoIin-2- yl)amino)pyrazine-2-carbonitrile- Compound 26 Synthesis of (E)-5-((4-amino-8-(4-(2-cyanovinyl)-2,6-dimethylphenyl)-6- fluoroquinazoIin-2-yl)amino)pyrazine-2-carbonitrile (compound 26) Compound 26 [0314] Compound 20d (92 mg, 0.21 mmol), 5-aminopyrazine-2-carbonitrile (60 mg, 0.50 mmol, Ark Pharm Inc, AK-21935), N,N-diisopropylethylamine (174 1 .0 mmol), (9,9- dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (24 mg, 0.042 mmol) and palladium (II) acetate (9 mg, 0.042 mmol) were combined under argon in N-methyl-2-pyrrolidone (2 mL). The reaction was heated at 100C in a sealed vessel for 7 hours. The reaction mixture was cooled down to room temperature, purified by silica gel chromatography (gradient from 50- 100% ethyl acetate in wo-hexanes) and then re-purified by reverse phase chromatography (5- 100% acetonitrile in water with 0.1 % trifluoroacetic acid) to afford the TFA salt of compound 26. ‘H NMR (400 MHz, DMSO-flfc) delta 9.10 (s, 1 H), 8.20 (s, 1 H), 7.74 (d, J = 16.7 Hz, 1 H), 7.77 – 7.60 (m, 2H), 7.57 (s, 2H), 6.56 (d, J = 16.7 Hz, 1 H), 1.94 (s, 6H). LCMS (m/z) 436.9 [M+H], Tr = 3.59 min (LCMS method 1 ).

The synthetic route of 5-Aminopyrazine-2-carbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GILEAD SCIENCES, INC.; INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY OF THE AS CR, V.V.I.; JANSA, Petr; SIMON, Tetr; LANSDON, Eric; HU, Yunfeng, Eric; BASZCZYNSKI, Ondrejj; DEJMEK, Milan; MACKMAN, Richard, L.; (185 pag.)WO2016/105564; (2016); 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. 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Safety of 5-Methylpyrazine-2-carboxylic acid

To a stirred suspension of 5-methyl-pyrazine-2-carboxylic acid (25 g, 181 mmol) in 540 mL THF at roomtemperature under N2 was added DIEA (31.7 mL, 181 mmol)resulting in a brown solution. Diphenyl phosphoryl azide(39.2 mL, 181 mmol) then was added dropwise as a solutionin 50 mL THF over 1 h behind a blast shield. The reac- tion was allowed to stir overnight. The reaction thenwas rotary evaporated to a small volume at room tempera- ture and partitioned between Et2O (1 L) and H20 (1 L) .The H2O layer was back extracted with 2 x 250 mL Et2O, andthe combined organics washed 2 x 1 L with sat’d Na2CO2.The organics were dried (MgSO4) , filtered, and concen- trated to a solid mass, which was triturated with Et2O togive the product as a yellow solid (15 g, 50%). Purercompound could be isolated by taking x g of the crudeproduct in 20x mL of Et2O, and treating with l-2x g ofdecolorizing carbon at room temperature for a few min- utes. After filtration and concentration, this materialwas homogeneous by TLC in EtOAc and pure white. The re- covery was typically 65%.

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; ICOS CORPORATION; WO2006/14359; (2006); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 8-Chloroimidazo[1,2-a]pyrazine

Example A15Mixture of 3-bromo-8-chloro-imidazo[1,2-c]pyrazine and 3,8-dibromo-imidazo[1,2-a]pyrazine N-Bromosuccinimide (2.0 g, 11.6 mmol) was added to a stirred solution of intermediate 3 (1.78 g, 11.58 mmol) in DCM (50 ml). The mixture was stirred at RT for 2 h. and then diluted with further DCM and washed with a saturated solution of sodium carbonate. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo to yield a 72/28 mixture of 3-bromo-8-chloro-imidazo[1,2-c]-pyrazine and 3,8-dibromo-imidazo[1,2-a]pyrazine (intermediate 15) (5.89 g, 99%) as white solid.

The synthetic route of 69214-33-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Pharmaceutica NV; US2012/329792; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem