Category: Pyrazines

6705-33-5, Adding some certain compound to certain chemical reactions, such as: 6705-33-5, name is Pyrazin-2-ylmethanol, 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 6705-33-5.

Example 1018; Step A; To a suspension of triphenylphosphine polystyrene (3 gm, 1 mmol/gm) in dry dichloromethane (20 ml) was slowly added bromine (154 muL). The resulting mixture was stirred at room temperature for 10 min, a solution of commercially available pyrazin-2-yl-methanol (114 mg) in dry dichloromethane (10 ml) was added and stirring at room temperature was continued for 21? h. The mixture was filtered, concentrated under reduce pressure at 20 C. and purified by flash chromatography (silica, cyclohexane/ethyl acetate). The obtained material was dissolved in dry N,N-dimethylformamide (1.5 mL) and added to a suspension of the title compound from Example 1007c (22.3 mg) and potassium carbonate (69.1 mg) in dry N,N-dimethylformamide (1.5 mL). The resulting mixture was stirred at room temperature for 16 h and then concentrated under reduce pressure. The remaining residue was purified by flash chromatography (silica, dichloromethane/methanol) to afford the title compound (6.8 mg; 25%) as a single isomer. [MH]+=539.

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 6705-33-5.

Reference:
Patent; ALANTOS PHARMACEUTICALS, INC.; US2007/155739; (2007); 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. 274-79-3 name is Imidazo[1,2-a]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. 274-79-3

Imidazo[1,2-a]pyrazine 4b (500 mg, 4.20 mmol) was dissolved in 5 mL of 2-methoxyethanol, followed by addition of platinum dioxide (100 mg, 0.36 mmol), and the reactor was purged with hydrogen for three times. After stirring for 12 hours, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure to obtain 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine 4c (200 mg, yield 38.7%) as a yellow oil. MS m/z (ESI): 124.1 [M+1]

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

Reference:
Patent; Jiangsu Hansoh Pharmaceutical Co., Ltd.; TANG, Pengcho; LI, Xin; LI, Xiangqin; CHEN, Yang; WANG, Bin; ZHU, Zhe; EP2604610; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

55557-52-3, 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 55557-52-3 as follows.

Step-1: (0930) Preparation of (3-chloropyrazin-2-yl)methanamine hydrochloride: (0931) [00352] To a solution of 3-chloropyrazine-2-carbonitrile (10 g) in acetic acid (100 mL) was added Raney Nickel (50% slurry in water, 10 g). The resulting mixture was stirred under 4 bar hydrogen pressure at room temperature for 15 h. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure and co-evaporated with toluene. The remaining brown solid was dissolved in ethyl acetate at 50 C and cooled on an ice-bath. 4M hydrochloric acid in dioxane (50 mL) was added and the reaction mixture was allowed to stir at room temperature for 18 h. The precipitate formed was collected by filtration, washed with diethyl ether and dried under reduced pressure. The product brown solid obtained was dissolved in methanol at 60 C and filtered. The filtrate was partially concentrated, cooled to room temperature and diethyl ether (500 mL) was added. The mixture was allowed to stir at room temperature 18 h. The solids formed were collected by filtration, washed with diethyl ether and dried under reduced pressure to afford the title compound (3-chloropyrazin-2- yl)methanamine hydrochloride (7.67 g, crude) as a brown solid. Calculated (M+H): 144.03; Found (M+H): 144.0

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 55557-52-3, and friends who are interested can also refer to it.

Reference:
Patent; LUC THERAPEUTICS; ANDERSON, David, R.; VOLKMANN, Robert, A.; MENNITE, Frank, S.; FANGER, Christopher; (390 pag.)WO2017/100591; (2017); A1;,
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

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

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

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. 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

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

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