Month: February 2021

Reference of 486460-21-3, 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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

DIPEA (0.307 mL, 1.759 mmol) was added to a mixture of 3-(trifluoromethyl)-5,6,7,8- tetrahydro-[ 1 ,2,4jtriazolo[4,3-ajpyrazine (127 mg, 0.660 mmol), cis-1 -(6-chloro-3- cyanoquinolin-4-yl)-2-methylpiperidine-4-carboxylic acid (145 mg, 0.440 mmol), and HATU(334 mg, 0.879 mmol) in DMF (4 mL) and stirred at 18 C for 3 h. The reaction was quenchedwith water (30 mL) and extracted with EtOAc (30 mL x 4), the combined organic phases were washed with brine (30 mL), dried over Na2SO4, filtered. The filtrates were concentrated and purified by p-HPLC to give cis-6-chloro-4-(2-methyl-4-(3-(trifluoromethyl)-5 ,6,7, 8-tetrahydro- [1 ,2,4jtriazolo [4,3-ajpyrazine-7-carbonyl)piperidin- 1 -yl)quinoline-3 -carbonitrile. MS: 504 (M + 1). The product was resolved by SFC (Column: Chiralpak AD-3 Mobile phase: A: CO2 B: methanol (0.05% DEA) Gradient: from 5% to 40% of B SFC separation gave peak 1(70mg, 0.135 mmol) MS: 504 (M + 1); and peak 2 (R,R or S,S) MS: 504 (M +1)

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; CUMMING, Jared, N.; DYKSTRA, Kevin, D.; HRUZA, Alan; LI, Derun; LIU, Hong; TANG, Haiqun; TAOKA, Brandon, M.; VERRAS, Andreas; WALSH, Shawn, P.; WU, Wen-Lian; (170 pag.)WO2018/34918; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4744-50-7,Some common heterocyclic compound, 4744-50-7, name is 2,3-Pyrazinecarboxylic anhydride, molecular formula is C6H2N2O3, 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.

5.1.26 13-[(Methyloxy)carbonyl]-2-pyrazinecarboxylic acid (35) 16 2,3-Pyrazinedicarboxylic anhydride (34) (15.3 g, 102 mmol) was dissolved in methanol (100 mL) and the solution was stood at room temperature for 3 days. The solvent was removed under reduced pressure and the residue was crystallised from ethyl acetate to give 35 (13.85 g, 75%): MS ES+ve m/z 183 (M+H)+; 1H NMR delta (DMSO-d6) 8.91 (1H, d, J 2 Hz), 8.90 (1H, d, J 2 Hz), 3.90 (3H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,3-Pyrazinecarboxylic anhydride, its application will become more common.

Reference:
Article; Procopiou, Panayiotis A.; Browning, Christopher; Gore, Paul M.; Lynn, Sean M.; Richards, Stephen A.; Slack, Robert J.; Sollis, Steven L.; Bioorganic and Medicinal Chemistry; vol. 20; 20; (2012); p. 6097 – 6108;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 95-89-6,Some common heterocyclic compound, 95-89-6, name is 3-Chloro-2,5-dimethylpyrazine, molecular formula is C6H7ClN2, 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.

Ammonia in water (3 mL, 48.5 mmol) was added to 3-chloro-2,5-dimethylpyrazine (0.121 mL, 1 mmol) and the mixture heated by microwaves to 165 C. for 7 hours. Following LCMS analysis, the reaction was then reheated to 165 C. for a further 16 hours, by microwaves. After cooling, the solvent was removed under a stream of nitrogen and the crude redissolved in dichloromethane (20 mL). Water (25 mL) was added and the mixture basified to pH14 using sodium hydroxide solution (18 N). The organic layer was removed and the aqueous layer extracted with dichloromethane (5¡Á25 mL). The organic phases were combined and dried using a hydrophobic frit, then evaporated in vacuo to give the title product (109 mg). This was used directly in the next step with no further purification. LCMS (2 min, high pH) Rt 0.47 min, m/z (ES+) 124 (M+H). 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 7.73 (s, 1H), 4.42 (br. s., 2H), 2.37 (s, 3H), 2.35 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloro-2,5-dimethylpyrazine, its application will become more common.

Reference:
Patent; Glaxo Group Limited; Birault, Veronique; Campbell, Amanda Jennifer; Harrison, Stephen; Le, Joelle; Shukla, Lena; US2015/65507; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, 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 6966-01-4, Application In Synthesis of Methyl 3-amino-6-bromopyrazine-2-carboxylate

Methyl 3-amino-6-bromo-pyrazine-2-carboxylate (334 mg), tert-butyl 4-[3-methyl-4- (4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)pyrazol- 1 -yl]piperidine- 1 -carboxylate (563 mg) and bis(triphenylphosphine) palladium (II) chloride (101 mg) and cesium fluoride (656 mg) in MeOH (11 mL) were degassed under vacuum and argon , stirred at 130 0C for 20mn under microwave conditions. The mixture wac concentrated and the residue was dissolved in dichloromethane and filtered. The filtrate was purified by flash chromatography on silica gel eluting with 50 to 100% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford methyl 3-amino-6-[l-(l-tert-butoxycarbonyl-4- piperidyl)-3-methyl-pyrazol-4-yl]pyrazine-2-carboxylate (421 mg). Mass spectrum: M+H+ 417. Retention time: 3.47min

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-6-bromopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AstraZeneca AB; AstraZeneca UK Limited; WO2009/24825; (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. 23611-75-8, name is Methyl 6-chloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of Methyl 6-chloropyrazine-2-carboxylate

A mixture of l-(4-((4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methyl)benzyl)pyridin-2(lH)-one (339 mg, 1.05 mmol, 3.0 eq), methyl 6-chloropyrazine-2-carboxylate (150 mg, 0.87 mmol, 1.0 eq), Pd(dppf)Ci2 (71 mg, 0.061 mmol, 0.1 eq), K2C03 (240 mg, 1.74 mmol, 2.0 eq) in toluene/dioxane/H20 (10 niL/1 niL/1 mL) under N2 was stirred at 100 C for 5 h and then concentrated. The residue was extracted with EA (50 mL X 3). The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified via pre-TLC to afford methyl 6-(4-((2-oxopyridin-l(2H)-yl)methyl)benzyl)pyrazine-2-carboxylate as a white solid (100 mg, 34%).

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 23611-75-8.

Reference:
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; WO2015/103317; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 6164-79-0, name is Methyl 2-pyrazinecarboxylate, molecular formula is C6H6N2O2, 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: C6H6N2O2

Pyrazine-2-carboxylic acid hydrazide. To a stirred solution of pyrazine-2-carboxylic acid methyl ester (11.1 g, 80 mmol) in 140 mL OF ETOH was added hydrazine hydrate (15.6 ML, 320 mmol). The resultant solution was heated to reflux for 2h. The solvent was removed under reduced pressure and dried under high vacuum to yield the title amide (11.1 g, 100%) as a white solid. The product was used in subsequent steps without purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6164-79-0, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/16909; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1416740-16-3, 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. 1416740-16-3 name is 2-Bromo-7-nitro-5H-pyrrolo[2,3-b]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 3; 2-hydroxy-N-(2-(4-(isopropylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7- yl)benzamide (Compound 1-14)METHOD C:Step 1: 2-bromo-7-nitro-5-trityl-pyrrolo[2,3-b]pyrazine [00203] 2-bromo-7-nitro-5H-pyrrolo[2,3-b]pyrazine (5 g, 20.57 mmol) was dissolved in DMF (100 mL) under N2. Solution was cooled in an ice bath and sodium hydride (867.1 mg, 22.63 mmol) added portionwise. After 30 minutes (effervescence completed) trityl chloride (6.022 g, 21.60 mmol) was added in one portion and the mixture allowed to warm to ambient temperature (Precipitate observed after around 15 mins). Reaction mixture was poured into water and mixture stirred for 1 hour then filtered. Solid was washed with copious water then dried in a vacuum oven over 48 hours at 80 C. Taken on to the next step as is. (9.7 g, 97.3%) XH NMR (400.0 MHz, DMSO) delta 8.46 (s, 1H), 8.40 (s, 1H), 7.38 – 7.36 (m, H), 7.23 – 7.20 (m, 8H) and 3.32 (s, 7H) ppm

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Bromo-7-nitro-5H-pyrrolo[2,3-b]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; MACCORMICK, Somhairle; STORCK, Pierre-henri; MORTIMORE, Michael, Paul; CHARRIER, Jean-damien; KNEGTEL, Ronald; YOUNG, Stephen, Clinton; PINDER, Joanne; DURRANT, Steven, John; WO2012/178123; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4774-14-5, 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 2,6-dichloropyrazine (2.5 g, 16.8 mmol, 1.0 equiv),/?- ? toluenesulfonic acid (6.4 g, 33.6 mmol, 2.0 equiv), sodium iodide (20.0 g, 133.3 mmol, 8.0 equiv), 15-crown-5 (2.0 mL) and sulfolane (40 mL) was heated at 150 0C and stirred in a sealed tube for 2 hr. After cooling, water (100 mL) was added to the reaction mixture. The mixture was then neutralized with a saturated solution of sodium hydrogencarbonate, and washed with a saturated solution of sodium thiosulfate. The mixture was extracted with diethyl ether (5 x 100 mL). The ether extracts were dried (Na2SO4) and concentrated in vacuo. 2,6-Diiodopyrazine was precipitated with 10 mL of water, filtered, washed with water and pentane to provide a pale yellow powder after lyophilization (2.1 g, 38%). 1H NMR (400 MHz, CDCl3) delta 8.74 (s, 2H); MS (M+H)+ = 332, R1= 1.29 min.

The synthetic route of 2,6-Dichloropyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; XENON PHARMACEUTICALS INC; WO2008/24390; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 123-32-0, name is 2,5-Dimethylpyrazine, 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 123-32-0, Application In Synthesis of 2,5-Dimethylpyrazine

(b) 3,6-Dimethylpyrazin-2-amine A mixture of 2,5-dimethylpyrazine (14 g, 0.13 mol) in N,N-dimethylaniline (50 mL) was heated to 170 C. and NaNH2 (22 g, 0.56 mol) was added in portions. The reaction mixture was stirred at 170 C. for 1 h, and the solvent was removed. The product was purified by silica gel column chromatography to give 3,6-dimethylpyrazin-2-amine as a brown solid (1.6 g, yield 10%). ESI MS: m/z 124 [M+1]+.

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

Reference:
Patent; Sunovion Pharmaceuticals Inc.; US2012/178748; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, 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 143591-61-1, Formula: C6H3BrClN3

A 33% (w/v) ethanol solution of methylamine (5.4 mL,130.55 mmol)was added to a solution of 3-bromo-8-chloroimidazo[1,2-a]pyrazine (500 mg, 2.15 mmol) in ethanol in a microwaveadaptedvial. The reaction was submitted to microwave irradiationsduring 20 min at 140 C. The solvent was removed underreduced pressure. The crude mixture was dissolved in ethyl acetateand successively washed with saturated aqueous chloride ammonium,distilled water and finally brine. The organic phase was driedon sodium sulphate, filtered and concentrated under reducedpressure. The compound is obtained as a white solid (92% yield). C7H7BrN4. Mw: 227.06 g/mol. Mp 145-146 C. 1H-RMN delta (ppm,400 MHz, DMSO-d6) 2.94 (d, 3H, NHCH3, J 6 Hz), 7.42 (d, 1H, CH 6,J 8 Hz), 7.52 (d, 1H, CH 7, J 8 Hz), 7.65 (m, 2H, NH, CH 2). 13CRMNdelta (ppm, 100 MHz, DMSO-d6) 22.77 (NHCH3), 97.83 (Cq 1),107.34 (CH 7),130.04 (CH 6),132.10 (CH 2),133.81 (Cq 3′),150.72 (Cq4). MS (ESI+ , QTof, m/z): 227.1 [M+H]+. HRMS calculated forC7H8BrN4 226.9932, found 226.9935.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Article; Patinote, Cindy; Bou Karroum, Nour; Moarbess, Georges; Deleuze-Masquefa, Carine; Hadj-Kaddour, Kamel; Cuq, Pierre; Diab-Assaf, Mona; Kassab, Issam; Bonnet, Pierre-Antoine; European Journal of Medicinal Chemistry; vol. 138; (2017); p. 909 – 919;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem