Pyrazines

4858-85-9, 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. 4858-85-9 name is 2,3-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.

Reference Production Example 19 A mixture of 3.73 g of 2,3-dichloropyrazine, 8.80 g of diethyl malonate, 30 ml of dimethyl sulfoxide and 17.9 g of cesium carbonate was stirred for 8 hours at 110C under a nitrogen atmosphere. The reaction mixture was allowed to cool to room temperature, then, to this was added ice water and extracted with ethyl acetate. The organic layer was washed with saturated brine twice, and dried over anhydrous magnesium sulfate, then, concentrated under reduced pressure. 3.67 g of the resultant residue was subjected to silica gel column chromatography, to obtain 2.69 g of diethyl (3-chloro-2-pyrazinyl) malonate. 1H-NMR (CDCl3, TMS) delta (ppm): 1.27 (6 H, t, J=7.2 Hz), 4.30 (4 H, q, J=7.2 Hz), 5.20 (1 H, s), 8.36 (1 H, d, J=2.6 Hz), 8.50 (1 H, d, J=2.6 Hz)

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

Reference:
Patent; Sumitomo Chemical Company, Limited; EP1958946; (2008); 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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., 486460-21-3

VI (2.0g, 5.0mmol) and 3- (trifluoromethyl) -5,6,7,8-tetrahydro – [1,2,4] triazolo [4,3-a] pyrazine (of 0.912 g , 4.7mmol) Was dissolved in 20ml of anhydrous N, N- dimethylformamide was added HOBt (0.770g, 5.7mmol) and EDC ¡¤ HCL (1.092g, 5.7mmol), stirred at room temperature 20h. After the reaction was added 20ml of water and 20ml of ethyl acetate, there Phase was washed with water 3 times, washed three times with saturated aqueous sodium carbonate solution, the organic phase was dried over anhydrous sodium sulfate, suction filtered, and concentrated to give yellow Colored foamy solid 2.967g, crude yield> 100%, recrystallized from ethyl acetate, filtration and drying to give a yellow solid 1.827g, Recrystallization yield of 63.6%.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Shanghai Institute Of Pharmaceutical Industry; China State Institute of Pharmaceutical Industry; Meng, Xiangguo; Cai, Zhengyan; Zhou, Weicheng; Jiang, Jingzhang; Zhu, Yijun; Ge, Yuanyuan; Yan, Pingping; (32 pag.)CN103172635; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

The chemical industry reduces the impact on the environment during synthesis 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life. 1458-18-0

To a suspension of methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate (IVa) (5.55 g, 25.0 mmol) in 2-propanol (50 mL) was added hexamethyleneimine (2.73 g, 3.1 0 mL, 27.5 mmol) and the mixture was stirred at room temperature. Diisopropyethylamine (3.55 g, 4.79 mL, 27.5 mmol) was then added and the reaction mixture was heated at reflux. After 2 h the reaction was allowed to cool to room temperature, which caused the product to crystallize. The solid product was collected by vacuum filtration and washed with cold 2-propanol followed by diethyl ether. After drying, the desired product (Ilia) was obtained as pink crystals (5.91 g, 83%).

The chemical industry reduces the impact on the environment during synthesis 1458-18-0. I believe this compound will play a more active role in future production and life.

Reference:
Patent; UNIVERSITY OF WOLLONGONG; KELSO, Michael; RANSON, Marie; BUCKLEY, Benjamin; ABOELELA, Ashraf; (103 pag.)WO2018/81863; (2018); 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. 20737-42-2, name is 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., 20737-42-2

Preparation of (S)-3-(4-cyanophenyl)-2-((4-(((5-fluoro-1H-benzo[d]imidazol- 2-yl)methyl)amino)-6-((3-((4-(3-hydroxypyrazine-2-carbonyl)piperazin-1- yl)methyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)-N,N-dimethylpropanamide (TA1021). HATU (1.2 equiv., 34 mg, 0.093 mmol) was added to a solution of 3-hydroxypyrazine-2- carboxylic acid (I-6, 1.1equiv., 12 mg, 0.080 mmol, Synthonix, Fisher Scientific) in anhydrous DCM (0.70 mL) and DIPEA (3equiv., 0.040 mL, 0.23 mmol). After being stirred at r.t. for 10 minutes, TA1013 (50 mg, 0.080 mmol) was added. The reaction was stirred at r.t. until the LCMS analysis showed complete consumption of the starting material (3-24h). The crude residue was then purified by reverse phase preparative HPLC (XBridge BEH, 19×150 mm, 5mum, C18 column; ACN/water with 0.1% formic acid modifier, 20mL/min), affording Compound TA1021 (17.3 mg, 29%) as an orange solid. 1H NMR (400 MHz, DMSO-d6) d 12.20 (s, 1H), 8.95 (d, J = 24.1 Hz, 1H), 8.07- 7.87 (m, 1H), 7.84- 7.68 (m, 1H), 7.68- 7.41 (m, 4H), 7.40- 7.22 (m, 2H), 7.22- 6.78 (m, 3H), 6.56 (s, 1H), 5.18- 4.91 (m, 1H), 4.79- 4.50 (m, 2H), 3.74- 3.39 (m, 7H), 3.28- 3.13 (m, 4H), 3.12- 2.78 (m, 5H), 2.75- 2.66 (m, 1H), 2.61 (s, 1H), 2.48- 2.02 (m, 4H). MS (m/z): 771 [M+1]+, LCMS purity: 99%.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; ADURO BIOTECH, INC.; KATIBAH, George Edwin; KIM, Jung Yun; NDUBAKU, Chudi Obioma; ROBERTS, Tucker Curran; TJANDRA, Meiliana; (165 pag.)WO2019/245910; (2019); 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. 486460-20-2, name is 3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine, A new synthetic method of this compound is introduced below., 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. H NMR (500 MHz, CDC13) 8 2.21 (br, 1H), 3.29 (t, 2H, J = 5.5 Hz), 4.09 (t, 2H, J = 5.5 Hz), 4.24 (s, 2H). MS (M+1) 193.

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; MERCK & CO., INC.; WO2004/58266; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common heterocyclic compound, 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, molecular formula is C6H7ClN4O2, 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. 1458-01-1.

Intermediate A. l : 3,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 1) and NaOH (6 mol/1 in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/1 in water; approx. 240 riiL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60¡ãC.C5H5CIN4O2ESI Mass spectrum: m z = 189 [M+H]+; m z = 187 [M-H]~

The synthetic route of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; KLEY, Joerg; HAMPRECHT, Dieter; HECKEL, Armin; (67 pag.)WO2016/113169; (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. 6164-79-0, name is Methyl 2-pyrazinecarboxylate, A new synthetic method of this compound is introduced below., 6164-79-0

Step 2; Lithium aluminum hydride (40.0 mg, 1.06 mmol) was suspended in tetrahydrofuran (1.0 mL). To this, a solution of methyl 2-pyrazinecarboxylate (66.0 mg, 0.478 mmol) in tetrahydrofuran (0.5 mL) was added dropwise under a nitrogen atmosphere at 0 C. and the mixture was stirred at the same temperature for 15 minutes. Then, water (40 muL), a 15% aqueous sodium hydroxide solution (40 muL) and water (120 muL) were successively added to the reaction mixture and the mixture was stirred at room temperature for 1 hour. The mixture was filtered through Celite and the mother liquid was concentrated. The residue was purified by silica gel column chromatography (chloroform/methanol=9/1) to give 2-pyrazinemethanol (Compound CD) (19.0 yield: 36%).1H-NMR (270 MHz, CDCl3, delta): 3.11 (brd, J=5.6 Hz, 1H), 4.85 (d, J=5.6 Hz, 1H), 8.52-8.55 (m, 2H), 8.64 (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; Amishiro, Nobuyoshi; Fukuda, Yuichi; Kinpara, Keisuke; Mie, Motoya; Tagaya, Hisashi; Takahashi, Takeshi; US2011/237584; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-18-0, 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. 1458-18-0 name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 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.

round bottomed flask was charged with methyl 6-amino 2,3-dichloro pyrazine 5-carboxylate (Aldrich, 25 g, 112.6 mmol), 2-S-ethyl piperazine (prepared as per Williams et al J. Med. Chem 1996, 39, 1345, 83% active, 15.7 g, 112.7 mmol), cesium carbonate (100 g, 300 mmol) and 1 ,4 dioxane (400 mL). The flask was equipped with a reflux condenser and heated to 8O0C. After 12hours the reaction was cooled, diluted with CH2CI2 (~ 200 mL), and filtered through celite. The filtrate was washed once with water and then concentrated to an oil. The crude product was purified by silica gel column chromatography (3% to 10% MeOH in CH2CI2) to afford compound A3 (30.8 g. 91 %). MS: M+H = 300

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; SCHERING CORPORATION; PHARMACOPEIA DRUG DISCOVERY, INC.; WO2006/88836; (2006); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

55557-52-3,Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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.

Step A: 3-[(4-Methoxybenzyl)amino]pyrazine-2-carbonitrile To a solution of 3-chloropyrazine-2-carbonitrile (500 mg, 3.6 mmol) in dichloromethane (DCM) (4.0 mL) was added, 4-methoxy-benzenemethanamine (470 muL, 0.0036 mol), N,N-diisopropylethylamine (620 muL, 0.0036 mol) and the resulting mixture was stirred at room temperature (25 C.) for 5 h. The crude residue was purified by flash column chromatography to yield the desired product (650 mg, 75%). MF=C13H12N4O; LCMS calculated for C13H13N4O(M+H)+: m/z=241.1.

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

Reference:
Patent; INCYTE CORPORATION; US2008/119491; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, A common compound: 33332-29-5, name is 2-Amino-5-chloropyrazine, 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.

EXAMPLE 1 3-(5-Chloro-2-pyrazinyl)-1-(2,6-dichlorobenzoyl)urea To a mixture of 250 mg. of 2-amino-5-chloropyrazine in 50 ml. of cold ethyl acetate was added 450 mg. of 2,6-dichlorobenzoylisocyanate and the mixture stirred overnight. The reaction product mixture was concentrated in vacuo to remove the ethyl acetate, and a mixture of ether and hexane added. The solid which precipitated was filtered off. The solid was recrystallized from ethanol to yield product having a melting point of about 201-204 C. The product was identified by elemental analyses and NMR and infrared spectra as 3-(5-chloro-2-pyrazinyl)-1-(2,6-dichlorobenzoyl)urea.

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, 2-Amino-5-chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Eli Lilly and Company; US4160834; (1979); A;; ; Patent; Eli Lilly and Company; US4083977; (1978); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem