Pyrazines

Reference of 36070-80-1, These common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-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.

A solution of 5-chloropyrazine-2-carboxylic acid (200.0 g, 1.26 mol) in THF (2.5 L) was treated with a solution of tert-butyl 2,2,2-trichloroacetimidate (460 mL, 2.57 mol) in cyclohexane (2.5 L). The reaction was stirred at 25 C for 5 min and then treated with boron trifluoride dimethyl etherate (144.0 mL, 126 mmol). The resulting reaction mixture was stirred at 25 C for 16 h and then diluted with EtOAc (5.0 L), washed with a saturated aqueous sodium bicarbonate solution (4.0 L) followed by water (5.0 L). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (Silica 60-120 mesh, 10% EtOAc in hexanes) to give tert-butyl 5-chloropyrazine-2-carboxylate (250 g, 92%) as a colorless oil. MS (ESI, positive ion) m/z: 215.2 (M+1 )+. 1H NMR (400 MHz, CDCl3) delta 9.01 (d, J = 1.3 Hz, 1 H), 8.70 (d, J = 1.3 Hz, 1 H), 1.66 (s, 9H).

Statistics shows that 5-Chloropyrazine-2-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 36070-80-1.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; AMEGADZIE, Albert; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Jian J.; CHENG, Yuan; FROHN, Michael J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul E.; LIU, Longbin; LIU, Qingyian; LOW, Jonathan D.; MA, Vu Van; MANNING, James; MINATTI, Ana Elena; NGUYEN, Thomas T.; NISHMURA, Nobuko; NORMAN, Mark H.; PETTUS, Liping H.; PICKRELL, Alexander J.; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; SIEGMUND, Aaron C.; STEC, Markian M.; WHITE, Ryan; XUE, Qiufen; (759 pag.)WO2016/22724; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1458-18-0, A common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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.

A solution of 2- (tributylstannyl) pyridine (1658.12 mg, 5.05 nMol, 2.00 equiv) , methyl 3-amino-5, 6-dichloropyrazine-2-carboxylate (500 mg, 2.525 nMol, 1 equiv) , Pd (PPh 3) 2Cl 2 (158.06 mg, 0.226 nMol, 0.1 equiv) and LiCl (190.94 mg, 5.05 nMol, 2 equiv) in 1, 4-dioxane (20 mL) was stirred for 16 hours at 90 under nitrogen atmosphere. This reaction was purification together with another batch E02189-006. The mixture was through a quick silica gel column chromatography, eluted with CH 2Cl 2 /MeOH (1: 1) to afford crude product. The resulting mixture was concentrated under reduced pressure. The residue was purified by Prep-TLC (CH 2Cl 2 /MeOH 30: 1) to afford methyl 3-amino-6-chloro-5- (pyridin-2-yl) pyrazine-2-carboxylate (180 mg, 30.20%) as a yellow solid. LCMS: m/z (ESI) , [M+H] + = 265.2. 1H NMR (300 MHz, DMSO-d 6) delta 3.9 (3H, s) , 7.5 (1H, ddd) , 7.6 -7.7 (2H, m) , 7.8 (1H, dt) , 8.0 (1H, td) , 8.7 (1H, ddd)

The synthetic route of 1458-18-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DIZAL (JIANGSU) PHARMACEUTICAL CO., LTD.; QI, Changhe; TSUI, Honchung; ZENG, Qingbei; YANG, Zhenfan; ZHANG, Xiaolin; (399 pag.)WO2020/35052; (2020); 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. 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, A new synthetic method of this compound is introduced below., Recommanded Product: tert-Butyl (5-methylpyrazin-2-yl)carbamate

Example 76; (3R)-1-{2-[(5-Methylpyrazin-2-yl)amino]-2-oxoethyl}-3-{[2-piperidin-1-yl-2-(2-thienyl)propanoyl]oxy}-1-azoniabicyclo[2.2.2]octane bromide (Isomer 1); a) 2-Bromo-N-(5-methylpyrazin-2-yl)acetamide; tert-Butyl 5-methylpyrazin-2-ylcarbamate (2.4 g) was heated in hydrochloric acid (50 mL) at 50 C. for 30 min. The brown solution was cooled to RT and made basic by addition of solid sodium carbonate. The products were then extracted with ethyl acetate (2×100 mL) and dried over magnesium sulfate. Concentration of the extracts gave a crude solid. The solid was dissolved in dry DMF (30 mL) and cesium carbonate (11.21 g) added. To the stirred mixture was added bromoacetylbromide and the mixture stirred at RT for 2 h. Water (200 mL) was added, and the mixture extracted with ethyl acetate (2×100 mL). Concentration of the extract to 50 mL and addition of isohexane (100 mL) gave the subtitled compound as a solid (1.640 g).1H NMR (400 MHz, DMSO) delta 11.06 (1H, s), 9.17 (1H, s), 8.31 (1H, d), 4.16 (2H, s), 2.46 (3H, s).

The synthetic route of 369638-68-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ford, Rhonan; Mete, Antonio; Millichip, Ian; Teobald, Barry; US2010/113510; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 16298-03-6, The chemical industry reduces the impact on the environment during synthesis 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, I believe this compound will play a more active role in future production and life.

Example 1 ; 3-Methyl-6-(4-(methvlsulfonvl)phenyl)-iV-phenvlpvrazine-2-carboxamide (Compound IV-1)SMETHOD A:Step 1: Methyl 3-amino-6-bromopyrazine-2-carboxylate [00141] A mixture of methyl 3-aminopyrazine-2-carboxylate (8.35 g, 54.53 mmol) and N- bromo-succinimide (9.705 g, 54.53 mmol) was stirred in MeCN (100 mL) at RT for 16 hours. The resultant precipitate was filtered, washed with MeCN and dried to give the desired product as a yellow solid (11.68 g, 92% Yield) XH NMR (400.0 MHz, DMSO) delta 3.85 (s, 3H), 7.55 (br s, 2H) and 8.42 (s, 1H) ppm; MS (ES+) 233.

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 2-aminopyrazine-3-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; KNEGTEL, Ronald, Marcellus Alphonsus; VIRANI, Aniza, Nizarali; REAPER, Philip, Michael; WO2011/143425; (2011); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 21943-17-9, name is 5-Bromo-3-chloropyrazin-2(1H)-one, 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 21943-17-9, Recommanded Product: 21943-17-9

General procedure: A solution of 56 (1.50 g, 7.16 mmol), the appropriate secondary amine (8.59 mmol, 1.20 equiv) and diisopropylethylamine (1.50 mL, 8.59 mmol) in n-butanol (15 mL)was heated in a microwave reactor using variable wattage to 140 C for 1 h. The mixture was concentrated and purified by flash column chromatography on silica, eluting with 9:1 dichloromethane/methanol, to give gave 58-63.

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-Bromo-3-chloropyrazin-2(1H)-one, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728,16;; ; Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 23229-25-6, These common heterocyclic compound, 23229-25-6, name is 2,6-Dibromopyrazine, 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.

19a) 4- (6-BROMO-PYRAZIN-2-YI)-MORPHOLINE PBr3 (11 g, 36.9 mmol, 5.5 eq) is added to 2, 6-dichloro-pyrazine (1.0 g, 6.7 mmol, 1 eq) at rt and heated to 150 °C for 24 h. This solution is dried in vacuum and the residue is dissolved in CH2CI2 (50 mL). The organics are washed with H20, brine and dried. Morpholine is added to this solution dropwise at 0 °C and warmed to rt in 5 h. The solution is washed with H20 and brine. Chromatography (SiO2, 10-60percent EtOAc-hexanes gradient elution) provides product 4-(6-BROMO-PYRAZIN-2-YL)-MORPHOLINE (0.5 g, 31 percent). MS/ESI, M+1 = 246.01, H NMR (400 MHz, CDCI3) 8 7.99 (s, 1 H), 7.95 (s, 1 H), 3.82 (t, J = 4.0 Hz, 4H), 3.58 (t, J = 4.0 Hz, 4H).

Statistics shows that 2,6-Dibromopyrazine is playing an increasingly important role. we look forward to future research findings about 23229-25-6.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2005/28444; (2005); 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. 22047-25-2, name is Acetylpyrazine, A new synthetic method of this compound is introduced below., Formula: C6H6N2O

Preparation 21-Pyrazin-2-yl-ethylamineThe synthetic procedure used in this preparation is outlined below in Scheme C. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.

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; Chen, Li; Dillon, Michael Patrick; Feng, Lichun; Yang, Minmin; US2010/324069; (2010); 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 41110-29-6 as follows. COA of Formula: C7H8N2O2

To a stirred solution of the product of Step A (0.9 g, 5.9 mmol) in MeOH (20 mL) was added hydrazine hydrate (1.5g, 23.7 mmol) at RT. The mixture was stirred at 60 C overnight. The mixture was concentrated and the residue was dissolved into EA (30 mL) . The organic phase was washed with brine, dried over Na2SO4and concentrated under reduced pressure. The residue (460 mg, yield: 51.1%) was used into next step directly. MS: M/e 153 (M+1)+.

According to the analysis of related databases, 41110-29-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BEIGENE, LTD.; ZHANG, Guoliang; SUN, Hanzi; ZHOU, Changyou; (253 pag.)WO2020/20097; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 63286-28-2, name is 2-Chloro-3-hydrazinylpyrazine, 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 63286-28-2, Recommanded Product: 2-Chloro-3-hydrazinylpyrazine

Add trifluoroacetic anhydride to the flask, use ethyl acetate as a solvent, stir in an ice bath, add ethyl acetate to intermediate b (5g, 0.0346mol) and sonicate to mix thoroughly, then slowly add trifluoroacetic anhydride. , Stir in an ice bath, check the progress of the reaction by spotting the plate. After the reaction, the solution was directly extracted with NaOH solution and ethyl acetate, and the organic phase was collected to be rotary-evaporated to obtain an oil. After drying, 10.9 g of a gray solid was obtained with a yield of 93.3%.

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

Reference:
Patent; Jiangxi Science and Technology Normal University; Zhu Wufu; Zheng Pengwu; Xu Shan; Liu Xiaobo; Zhang Qian; Zhou Lingjia; Han Haoyun; Yu Li; Zhou Hualan; Qiu Yufeng; (25 pag.)CN110467616; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 912773-24-1, name is 6-Bromoimidazo[1,2-a]pyrazine, 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. Product Details of 912773-24-1

Synthesis of 6-bromo-3-iodoimidazo[ 1 ,2-a]pyrazineA degassed solution of 6-bromoimidazo[l,2-a]pyrazine (500 mg, 2.52 mmol) and NIS (852 mg, 3.79 mmol) in DMF (10 mL) was heated to 60 C for 10 hours. The reaction mixture was cooled to RT and extract with DCM. The organics were washed with Na2S203 (aq), brine and dried over Na2S04. After concentrated, the crude product was purified by column (PE : EtOAc = 5 : 1) to obtain 6-bromo-3-iodoimidazo[l,2-a]pyrazine (530 mg, yield: 65%). 1H-NMR (CDC13, 400 MHz) delta 8.75 (s, 1H), 8.18 (s, 1H), 7.82 (s, 1H). MS (M+H)+: 324 / 326.

The synthetic route of 6-Bromoimidazo[1,2-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MCCOMAS, Casey Cameron; LIVERTON, Nigel J.; HABERMANN, Joerg; KOCH, Uwe; NARJES, Frank; LI, Peng; PENG, Xuanjia; SOLL, Richard; WU, Hao; PALANI, Anandan; DAI, Xing; LIU, Hong; HE, Shuwen; DANG, Qung; WO2013/34048; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem