Month: August 2021

Reference of 5049-61-6,Some common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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.

To a solution of 2-aminopyrazine (1.0 g, 10.5 mmol) in dioxane (25 mL) was added ethyl 3-bromo-2-ketopropionate (2.0 g, 10.5 mmol). The reaction was stirred at 50 C for 16 h. The mixture was filtered and the solid was washed with two portions of ethyl acetate. The solid was heated in 35 ML of isopropanol at reflux temperature for 4 h. The reaction mixture was concentrated and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous phase was extracted with three portions of ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate, and concentrated. Purification by chromatography (Biotage system, silica gel, ethyl acetate then 10% methanol/ethyl acetate) gave the title compound as a solid.

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

Reference:
Patent; MERCK & CO., INC.; WO2004/58266; (2004); 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 61892-95-3 as follows. COA of Formula: C6H8N2O

To a solution of (5-methylpyrazin-2-yl)methanol (500 mg, 4.028 mmol, commercial source: Combi- Blocks) in dichloromethane (20 mL), thionyl chloride (0.35 mL, 4.825 mmol, Commercial source: Avra) was added slowly at 0 C. The reaction mixture was allowed to reach 26 C and stirred for 16 h at the same temperature. Upon completion, the reaction mixture was concentrated under reduced pressure. The residue was neutralized with saturated sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic solution was dried over Na2S04, filtered and the filtrate was concentrated under reduced pressure to afford 2- (chloromethyl)-5-methylpyrazine (500 mg, crude) as a brown liquid.1H NMR (400 MHz, CDCI3) delta 8.60 (s, 1 H), 8.43 (s, 1 H), 4.67 (s, 2H), 2.59 (s, 3H). MS m/z [M+H]+= 143.04

According to the analysis of related databases, 61892-95-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ALEMPARTE-GALLARDO, Carlos; ENCINAS, Lourdes; ESQUIVIAS PROVENCIO, Jorge; (206 pag.)WO2019/34729; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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. name: (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

Step C – Synthesis of Intermediate Compound Int-7cTo a solution of (i?)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (6.16 g, 33.4 mmol) in THF (60 mL) was added TBAI (617 mg, 1.67 mmol). The mixture was cooled to -78 °C and a solution of rc-BuLi (14.7 mL, 2.5M in hexanes, 36.75 mmol) was slowly added over 10 minutes. The reaction mixture was allowed to stir at -78 °C for 30 minutes, then Int-7b in THF (20 mL) was slowly added over 10 minutes. The reaction was allowed to stir at -78 °C for 2 hours then allowed to warmed to room temperature and allowed to stir for about 15 hours. The reaction was quenched by addition of MeOH (5 mL), concentrated in vacuo, water added (50 mL) followed by diethyl ether (50 mL) and the layers were separated. The organic layer was washed with water (2 x 50 mL) then dried over Na2S04, filtered and concentrated in vacuo to provide the crude product. Further purification by column chromatograpy on a 330 g ISCO Redi-Sep silica gel column using a eluent of CH2C12 with a gradient of 0-10percent EtOAc/hexanes afforded the desired product Int-7c as a light amber oil (8.65 g, 63percent). 1H NMR (CDC13) ? 4.07-3.99 (m, 1H), 3.94- 3.89 (m, 1H), 3.79-3.71 (m, 2H), 3.68-3.63 (m, 6H), 2.32-2.17 (m, 1H), 1.25-1.21 (m, 1H), 1.06-0.95 (m, 5H), 0.88 (s, 10H), 0.74-0.68 (m, 1H), 0.69-0.66 (m, 2H), 0.12-0.02 (m, 12H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109838-85-9, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DWYER, Michael, P.; KEERTIKAR, Kartik, M.; ZENG, Qingbei; MAZZOLA, Robert, D., Jr.; YU, Wensheng; TANG, Haiqun; KIM, Seong Heon; TONG, Ling; ROSENBLUM, Stuart, B.; KOZLOWSKI, Joseph, A.; NAIR, Anilkumar Gopinadhan; WO2013/39876; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

59489-71-3, name is 2-Amino-5-bromopyrazine, 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. name: 2-Amino-5-bromopyrazine

A mixture of 5-bromopyrazin-2-amme (2.Og, 11.56mmol) and sodium thiomethoxide(1.62g, 23.12mmol) in dry dimethyl formamide (29ml) was stirred and heated at 1000C under nitrogen for 20 hours. The solvent was removed in vacuo and the residue treated with distilled water. The aqueous solution was extracted with DCM (3 times). The organics were combined dried with anhydrous sulphate, filtered and evaporated to give the title compound as a brown solid (1.12g, 69%). NMR (CDCl3): 2.75 (s, 3H), 4.65 (s, 2H), 8.13 (s, IH), 8.2 (s, IH); m/z 142.

The synthetic route of 59489-71-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/95159; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 186534-02-1, 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. 186534-02-1, name is 3,5,6-Trimethylpyrazine-2-carbaldehyde belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 3,5,6-trimethylpyrazine-2-carbardehyde (4.51 g, 30.0 mmol), 2- methyl-2-butene (12.8 mL, 120 mmol), and sodium dihydrogen phosphate 78ehydrate (4.68 g, 30.0 mmol) in /ert-butanol (90 mL) and water (30 mL) was added 80% sodium chlorite (10.2 g, 90.0 mmol) portionwise at 0 C. After being stirred at room temperature for 50 min, the reaction mixture was poured into 2N aqueous hydrochloric acid. The mixture was extracted with chloroform and the organic layer was dried over sodium sulfate, filtrated and concentrated in vacuo to give 3,5,6- trimethylpyrazine-2-carboxylate. MS (ESI): m/z 165 (M-H).

The synthetic route of 3,5,6-Trimethylpyrazine-2-carbaldehyde has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MITSUBISHI TANABE PHARMA CORPORATION; KAWANISHI, Eiji; HONGU, Mitsuya; TANAKA, Yoshihito; WO2011/105628; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1053656-22-6, name is 7-tert-Butyl 2-ethyl 5,6-dihydroimidazo[1,2-a]pyrazine-2,7(8H)-dicarboxylate, molecular formula is C14H21N3O4, 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. category: Pyrazines

[0097] Method C-Step j: Preparation of ethyl 5,6,7,8-tetrahydroimidazo[l,2-a] pyrazine-2- carboxylate [0098] 7-Tert-butyl 2-ethyl5,6-dihydroimidazo[l,2-a]pyrazine -2,7(8H)-dicarboxylate (50 mg, 0.17 mmol) was dissolved in 3 mL of 3M HCl in ethyl acetate. The mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered and washed with ethyl acetate. The solid was dissolved in water and added saturated NaHCC>3 aqueous solution until pH = 7. The solution was applied to reverse phase chromatography to afford the final compound as a white solid (27.53 mg, 83%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1053656-22-6, its application will become more common.

Reference:
Patent; ZHANG, Xiaohu; WO2014/113191; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1159811-97-8, 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 1159811-97-8 as follows.

6-Bromo-2-methylimidazo[1,2-a]pyrazine (5 g, 23.58 mmol) and sodium acetate (9.67 g, 117.9 mmol) were dissolved in acetic acid (25 mL) and water (25 mL). Aqueous formaldehyde (37%, 18 mL, 241.77 mmol) was added and the reaction mixture wasstirred at 80C for 1 h, then left to stand at room temperature for 15 h. The reaction mixture was stirred at 80C for a further 4 h, then left to stand room temperature for 15 h. The solid that formed was collected by filtration and washed with water (30 mL). A second batch of solid was obtained from the filtrate and washed with water (30 mL). A third batch of solid was obtained from the filtrate and washed with water (30 mL). Thesolids were combined and dried in vacuo to afford the title compound (4.31 g, 75.5%) as a white solid. H (500 MHz, DMSO-d6) 8.80 (d, J 1.1 Hz, 1H), 8.68 (d, J 1.2 Hz, 1H), 5.29 (t,J5.5 Hz, 1H), 4.81 (d,J5.2 Hz, 2H), 2.43 (s, 3H). LCMS m/z242.

According to the analysis of related databases, 1159811-97-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UCB BIOPHARMA SPRL; ALEXANDER, Rikki Peter; BENTLEY, Jonathan Mark; BRACE, Gareth Neil; BROOKINGS, Daniel Christopher; CHOVATIA, Praful Tulshi; DEBOVES, Herve Jean Claude; JOHNSTONE, Craig; JONES, Elizabeth Pearl; KROEPLIEN, Boris; LECOMTE, Fabien Claude; MADDEN, James; MILLER, Craig Adrian; PORTER, John Robert; SELBY, Matthew Duncan; SHAW, Michael Alan; VAIDYA, Darshan Gunvant; YULE, Ian Andrew; WO2015/86506; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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.

General procedure: To a solution of 2-amino-5-cyanopyridine (2b) (1190 mg, 10.0mmol) in tetrahydrofuran(100 mL), iodomethane (2.83 mL, 45.5mmol) was added andthe mixture was stirred at 0 C. The mixture was slowly addedto sodium hydride (60% in oil, 1440 mg, 36.0mmol) and stirredfor 12 h. To the reaction mixture was added methanol (20mL) to quench the reaction. Further, the reaction mixture wasdiluted with water and extracted with ethyl acetate (3 200mL). The combined organic layers were dried over Na2SO4,filtered, and the solvents were concentrated under reduced pressure.The obtained residue was purified by silica gel columnchromatography (hexane/ethyl acetate = 1/1) to yield dimethylamino 3b (1120 mg, 7.62mmol, 76%) as a dark brown 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:
Article; Saito, Ryohei; Kuchimaru, Takahiro; Higashi, Shoko; Lu, Shijia W.; Kiyama, Masahiro; Iwano, Satoshi; Obata, Rika; Hirano, Takashi; Kizaka-Kondoh, Shinae; Maki, Shojiro A.; Bulletin of the Chemical Society of Japan; vol. 92; 3; (2019); p. 608 – 618;,
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. 5900-13-0, name is 5-Bromo-3-methoxypyrazin-2-amine, A new synthetic method of this compound is introduced below., Safety of 5-Bromo-3-methoxypyrazin-2-amine

To a stirring solution of 5-bromo-3-methoxypyrazin-2-amine (1.50 g, 7.35 mmol) in pyridine (15 mL), DMAP (15 mg, 0.12 mmol) and (3,5-dichlorophenyl)methanesulfonyl chloride (1.91 g, 7.34 mmol) was added. The reaction was left stirring at room temperature under nitrogen for 2 hrs. A further addition of (3,5-dichlorophenyl)methanesulfonyl chloride (0.20 g, 0.77 mmol) was added to the reaction mixture which was then left stirring for 1 hr at room temperature. The reaction mixture was concentrated in vacuo resulting in a viscous orange mixture which was then diluted with EtOAc (100 mL), washed with water (2 x 80 mL), the organic layer was dried over Na2S04 and concentrated in vacuo to afford an orange solid. This was dissolved in EtOAc (30 mL) and acidified with HCl (2M, 20 mL) which resulted in the precipitation of the title compound as a white solid . The organic and aqueous layer were subsequently separated, the organic layer was washed with water (3 x 30 mL), dried over Na2S04 and concentrated in vacuo to afford a second crop of the title compound as an orange solid (combined yield 1.73g, 54%); H NMR (500 MHz, DMSO) delta 3.93 (s, 3H), 4.88 (s, 2H), 7.36 (d, 2H), 7.63 (m, 1H), 8.12 (s, 1H), 10.80 (s, 1H).

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; ACTIVE BIOTECH AB; FRITZSON, Ingela; LIBERG, David; EAST, Stephen; MACKINNON, Colin; PREVOST, Natacha; WO2014/184234; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5521-58-4, name is 5-Methylpyrazin-2-amine, 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

l-Chloro-N,N.2-trimethyl-prop-l -en- 1 -amine (0.26 mL, 2.0 mmol) was added to a solution 5 of 3-[(2S)-l-(difluoromethoxy)propan-2-yl]oxy-5-phenylmethoxy-benzoic acid (0.54 g,1.5 mmol) in DCM (20 mL) and stirred for 1 hour. 5-Methylpyrazin-2-amine (ClambdaS no.5521-58-4) (335 mg, 3.1 mmol) then pyridine (0.25 mL, 3.1 mmol) were added and the reaction stirred for a further 30 minutes before being reduced in vacuo and partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was further extracted K) into ethyl acetate (50 mL) and the combined organics washed with water (50 mL), brine(50 mL), dried (MgSO4), and reduced in vacuo. The crude residue was chromatographed on silica, eluting with 40-100% ethyl acetate in isohexane, to give the desired compound(0.48 g).1H NMR delta (CDCl3): 1.39 (d, 3H), 2.58 (s, 3H), 3.96 – 4.05 (m, 2H), 4.63 – 4.70 (m, IH), 15 5.13 (s, 2H), 6.30 (t, I H), 6.78 (t, IH), 7.09 (t, IH), 7.16 (t, IH), 7.35 – 7.48 (m, 5H), 8.17(s, IH), 8.39 (s, IH), 9.58 (d, IH); m/z 444 (M+H)+

The synthetic route of 5521-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2008/50117; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem