Category: Pyrazines

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 5049-61-6 as follows. 5049-61-6

Reference Synthesis Example 5 3,5-Dibromopyrazin-2-amine (42) (known compound, Reference: P. Jeanjot, et al., Synthesis, 513-522 (2003)) To a solution of aminopyrazine (4l) (10.0 g, 105 mmol) in DMSO (200 mL) and water (5 mL) was added N-bromosuccinimide (39.3 g, 221 mmol) at room temperature, and the mixture was stirred for 23 hours. To the mixture was added water and the product was extracted with diethyl ether (300 mL*4). The combined organic extract was washed successively with water (400 mL*2) and brine (500 mL*2), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (silica gel 280 g, n-hexane/dichloromethane/ethyl acetate=5/4/1). The resulting solid was further purified by recrystallization (n-hexane/ethyl acetate) to give Compound 42 (17.3 g, 68.3 mmol, 64.9%) as a colorless solid. Rf=0.48 (n-hexane/dichloromethane/ethyl acetate=5/4/1); 1H NMR (400 MHz, CDCl3) delta 5.05 (s, 2H), 8.05 (s, 1H).

According to the analysis of related databases, 5049-61-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JNC CORPORATION; NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY; US2011/244481; (2011); A1;,
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. 19745-07-4, name is 2,5-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 19745-07-4

To an NMP (7.5 ml) solution of 1.51 g of 2,5-dichloropyrazine were added 2.00 g of 1-(t-butoxycarbonyl)piperazine and 2.00 g of potassium carbonate, followed by 1 hour of stirring under heating at 100¡ãC. The mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous magnesium sulfate, and thereafter, the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 2.73 g of 2-chloro-5-(4-t-butoxycarbonylpiperazin-1-yl)pyrazine. Using this compound, 2-chloro-5-{4-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]piperazin-1-yl}pyrazine was obtained in a similar manner to Example 14 as colorless crystals.

The synthetic route of 19745-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP1396487; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

486424-37-7, A common compound: 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

1- (3-DIMETHYLAMINOPROPYL)-3-ETHYLCARBODIIMIDE hydrochloride (0.68 g, 3.5 mmol) was added in one portion to a stirred suspension of 2-MORPHOLIN-4-YLETHANAMINE (0.422 g, 3.2 mmol), 3-amino-6-bromopyrazine-2-carboxylic acid (0.64 g, 3.0 mmol; described in: Ellingson, R. C.; Henry, R. L. J. Am. Chem. Soc. 1949,2798-2800), and 1- hydroxybenzotriazole hydrate (0.48 g, 3.5 mmol) in acetonitrile (25 mL) at 0 C. The cooling bath was removed and stirring was continued at room temperature for 7 h. The solid was filtered off, washed with acetonitrile and purified by column chromatography on silica using methylene CHLORIDE/METHANOL/TRIETHYL amine, (95: 5: 0.1), to give 0.68 g (69% yield) of the title compound : 1H NMR (DMSO-d6, 400 MHz) 8 8.53 (m, 1 H), 8.34 (s, 1 H), 8.68 (br s, 2 H), 3.57 (t, J = 5 Hz, 4 H), 3.37 (q, J = 7 Hz, 2 H), 2.47 (q, J = 7 HZ, 2 I-, 2.40 (m, 4 H); MS (ES) M/Z 330 and 332 (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, 3-Amino-6-bromopyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTRAZENECA AB; WO2004/55009; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6966-01-4, The chemical industry reduces the impact on the environment during synthesis 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

Preparation of methyl 3,6-dibromopyrazine-2-carboxylate A mixture of 3 – amino – 6 – bromopyrazine – 2 – carboxylic acid methyl ester (4 ? 6 2 g ’20 mmol), aqueous hydrobromic acid (48%, 24 ml) and acetic acid (3.2 ml) was added to the reactor, -5 C. The solution (20 ml) of the solution of acetic acid (5 ml) and sodium nitrite (4.8 g, 70 ml) was slowly added successively -5 C stirring reaction lh. The reaction was terminated, washed with saturated sodium sulfite solution, extracted with ethyl acetate and water, washed with saturated NaCl solution and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as an off-white solid.

The chemical industry reduces the impact on the environment during synthesis Methyl 3-amino-6-bromopyrazine-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; NANJING SHENGHE PHARMACEUTICAL CO., LTD.; WANG, YONG; ZHAO, LIWEN; LIU, YANG; ZHANG, JINGZHONG; WANG, DEZHONG; GAO, YIPING; CHEN, HONGYAN; ZHANG, CANG; ZHANG, DI; (68 pag.)TWI523856; (2016); B;,
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 873-42-7 as follows. 873-42-7

To a stirred solution of 3,5-dichloropyrazin-2-amine X-10a (0.80 g, 4.15 mmol) in MeOH (20 mL) was added NaOMe (0.90 g, 16.6 mmol) at room temperature. The reaction mixture was heated at 70 C for 16h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was concentrated under vacuum. The residue was diluted with H20 (15 mL) and extracted with EtOAc (3 c 25 mL). The organic layer was separated, dried over anhydrous Na2S04 and concentrated under vacuum. The crude obtained was purified by combi flash chromatography (20% EtOAc in hexane) to afford 5- chloro-3-methoxypyrazin-2-amine X-10 (0.53 g) as an off-white solid. (0854) Yield: 69%. (0855) 1H NMR (400 MHz, DMSO-cfe) d 3.89 (s, 3H), 6.52 (brs, 2H), 7.53 (s, 1 H).

According to the analysis of related databases, 873-42-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UCB PHARMA GMBH; PEGURIER, Cecile; PROVINS, Laurent; CARDENAS, Alvaro; LEDECQ, Marie; MUELLER, Christa E.; HOCKEMEYER, Joerg; EL-TAYEB, Ali; BOSHTA, Nader; RASHED, Mahmoud; (165 pag.)WO2019/243303; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 24241-18-7 name is 2-Amino-3,5-dibromopyrazine, 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. 24241-18-7

Preparation of compound 36a: 3,5-dibromopyrazin-2-olTo a stirred solution of 3,5-dibromopyrazin-2-amine (30 g, 0.12 mol) in AcOH (300 ml_) was added dropwise cone. H2SO4 (50 ml_) at 15-25 0C. To the resulting solution was then added dropwise a solution of NaNO2 (16.6 g, 0.24 mol) in water (100 ml_) at 10-15 0C during a period of 1.5 h. After the addition, the resulting mixture was stirred at 10-15 0C for 1 h. The reaction mixture was poured into water (3 L) and extracted with EtOAc (1 L x 3). The combined organic layers were washed with saturated NaHCOs (1 L x 3) and brine (1 L) in sequence, dried over Na2SO4 and concentrated in vacuo which gave the title compound 36a as a yellow solid (24 g, 79.4%). 1H NMR (400 MHz, CDCI3): 7.44 (s, 1 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-3,5-dibromopyrazine, and friends who are interested can also refer to it.

Reference:
Patent; PFIZER INC.; NINKOVIC, Sacha; BRAGANZA, John Frederick; COLLINS, Michael Raymond; KATH, John Charles; LI, Hui; RICHTER, Daniel Tyler; WO2010/16005; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, name is 2-Amino-5-chloropyrazine, 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. 33332-29-5

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).

Statistics shows that 33332-29-5 is playing an increasingly important role. we look forward to future research findings about 2-Amino-5-chloropyrazine.

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

33332-29-5, These common heterocyclic compound, 33332-29-5, name is 2-Amino-5-chloropyrazine, 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: 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).

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 33332-29-5.

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

Adding a certain compound to certain chemical reactions, such as: 5049-61-6, name is Pyrazin-2-amine, 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 5049-61-6, 5049-61-6

Under absence of light and at 0 C., N-bromosuccinimide (15.68 g, 88.1 mmol) was added to a solution of 2-aminopyrazine (4.19 g, 44.06 mmol) in dry dichloromethane (250 ml). The mixture was stirred for 20 h at 4 C. and then washed with four 40 ml portions of a saturated sodium carbonate solution in water. The organic layer was dried (MgSO4) and evaporated under reduced pressure, affording the title compound as 12.8 g of a light brown solid. Column chromatography, using silica and a dichloromethane/ethyl acetate (3/1) mixture as the eluent, yielded pure 2-amino-3,5-dibromopyrazine as 5.00 g (65%) of a light yellow solid. 1H-NMR (CDCl3, 400 Mhz): 8.09 (s, I H), 4.95 (211, NH) ppm. 13C-NMR (CDCl3): 153.5 (C-2), 144.3, 131.9, 126.8 ppm.

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, Pyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NDSU-Research Foundation; US2011/28721; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

486460-20-2, name is 3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]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. 486460-20-2

3-(Trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine (540 mg, 2.87 mmol, from Step A) was hydrogenated under atmospheric hydrogen with 10% Pd/C (200 mg) as a catalyst in ethanol (10 mL) at ambient temperature for 18 h. Filtration through Celite followed by concentration gave a dark colored oil. Dichloromethane was added to the above oil and the insoluble black precipitate was filtered off. Concentration of the filtrate gave the title compound as an oil (495 mg). 1H NMR (500 MHz, CDCl3) delta 2.21 (br, 1H), 3.29 (t, 2H, J=5.5 Hz), 4.09 (t, 2H, J=5.5 Hz), 4.24 (s, 2H). LC/MS (M+1) 193

Statistics shows that 486460-20-2 is playing an increasingly important role. we look forward to future research findings about 3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine.

Reference:
Patent; Merck Sharp & Dohme Corp.; Edmondson, Scott D.; Fisher, Michael H.; Kim, Dooseop; Maccoss, Malcolm; Parmee, Emma R.; Weber, Ann E.; Xu, Jinyou; US2015/359793; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem