Category: Pyrazines

63744-22-9, 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. 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a stirred suspension of intermediate example 1-1 6,8-dibromo-imidazo[1,2-a]pyrazine (489 g, 1766 mmol) in MeOH (2900 mL) at -20 C. was dropwise added a solution of sodium methan thiolate (225 g, 3214 mmol, 1.8 eq) in 800 mL water. After stirring overnight, the clear solution was poured on 30 L water and the yellowish precipitate was filtered, washed with 3 L water and dried in vaccuo to yield 301 g 6-bromo-8-methylsulfanyl-imidazo[1,2-a]pyrazine (69.8%). 1H-NMR (300 MHz, d6-DMSO): delta=8.64 (1H, s), 8.00 (1H, d), 7.66 (1H, d2.54 (3H, s) ppm.

The synthetic route of 63744-22-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; Koppitz, Marcus; Klar, Ulrich; Jautelat, Rolf; Kosemund, Dirk; Bohlmann, Rolf; Bader, Benjamin; Lienau, Philip; Siemeister, Gerhard; US2013/281460; (2013); 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. 13301-04-7, name is Methyl 3,6-dibromopyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., 13301-04-7

Step 1: Synthesis of compound (B) as described in the general reaction scheme; 3,6-dibromo-pyrazine-2-carboxylic acid LiOH (655 mg, 27 mmol) is added to a solution of 3,6-dibromo-pyrazine-2-carboxylic acid methyl ester (A) (J. Med. Chem. 1969, 12, 285-87) (2.7 g, 9 mmol) in THF:water:MeOH (18:4.5:4.5 mL). The reaction is stirred at 5 C. for 30 min, concentrated in vacuo, taken up in DCM and washed with 1N HCl. The organic phase is dried over anhydrous MgSO4 and concentrated in vacuo to afford compound (B). 1H NMR (250 MHz, CDCl3) delta ppm 8.70 (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; WIGERINCK, Piet Tom Bert Paul; ANDREWS, Martin James Inglis; De WEER, Marc Maurice Germain; SABOURAULT, Nicholas Luc; KLUGE, Stefan Christian; US2011/118269; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

98-97-5, Adding a certain compound to certain chemical reactions, such as: 98-97-5, name is Pyrazine-2-carboxylic acid, 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 98-97-5.

(a) 2-pyrazine carboxylic acid, 104.3 gm, and 105.9 gm thionyl chloride were added to 800 ml methylene chloride and 5 ml dimethylformamide. The system was heated to reflux, at which point gas evolution took place. The system was stirred at reflux until gas evolution ceased, after about 5 hours, to give the 2-pyrazine carboxylic acid chloride. The solution was cooled to room temperature and transferred to a dropping funnel for use in Step (b) without further isolation.

According to the analysis of related databases, 98-97-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Chevron Research Company; US4504484; (1985); A;; ; Patent; Chevron Research Company; US4588735; (1986); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1, 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 36070-80-1 as follows.

In a sealed tube, Intermediate 30 (0.58 g, 1.079 mmol) was dissolved in DMF (5.39 mL). To the resulting solution was added 5-chloropyrazine-2-carboxylic acid (0.188 g, 1.187 mmol), HATU (0.615 g, 1.618 mmol), and pyridine (0.262 mL, 3.24 mmol). The reaction was stirred at 20 C. for 2 hours. The reaction was extracted into ethyl acetate, washed once with water, once with brine, dried with sodium sulfate, filtered through a fritted funnel, and concentrated. The crude material was eluted through a silica gel column using 0-50% EtOAc/Heptane. The desired fractions were combined and concentrated to yield tert-butyl N-[(4aR,6S,11bR)-10-[(5-chloropyrazine-2-carbonyl)amino]-3,3,6,11b-tetramethyl-4,4-dioxo-5,6-dihydro-4-aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (0.640 g, 0.944 mmol, 87% yield) as an off-white solid.

According to the analysis of related databases, 5-Chloropyrazine-2-carboxylic acid, the application of this compound in the production field has become more and more popular.

Reference:
Patent; WHITE, Ryan; ALLEN, Jennifer R.; EPSTEIN, Oleg; HONG, Fang-Tsao; HUA, Zihao; HUMAN, Jason Brooks; LOPEZ, Patricia; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; TAMAYO, Nuria A.; ZHENG, Xiao Mei; US2014/213581; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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 486460-21-3. 486460-21-3

((c/s-1-(3-Chlorophenyl)-4-f3-(trifluoromethyl)-5.6-dihvdrori.2.4ltriazolof4.3-a1pyrazin- 7(8H)-yl1cvclohexyl)methyl)-carbamic acid tert-butyl ester and ((^ra/7s-1-(3-chlorophenyl)-4- f3-(triflupsilonoromethyl)-5.6-dihvdrof1.2.41triazolof4.3-a1pyrazin-7(8H)-vncvclohexyl>methyl)- carbamic acid tert-butyl esterSodium triacetoxyborohydride (316mg, 1.49mmol) was added to a solution of [1-(3- chlorophenyl)-4-oxo-cyclohexylmethyl]-carbamic acid tert-butyl ester (360mg, 1.07mmol) and 3-trifluoromethyl-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]pyrazine (286.4mg, 1.49mmol) in 1 ,2-dichloroethane and the mixture was stirred at room temperature for 24h. The reaction was quenched with water and the product was extracted with ethyl acetate. The organic extracts were washed with brine, dried and concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography (silica, eluting with 1 :33:66 2M ammonia in methanol:ethyl acetatexyclohexane) to afford the individual title compounds as white solids.Cis diastereoisomer:MS (ES+): 514[M+H]+.TR [HPLC, Phenomenex Luna 3 micron C18; 5-95% CH3CN+0.1%Formic acid/H2O+0.1%Formic acid for 5 min, flow 2.0 ml/min]: 3.70 min.Trans diastereoisomer:MS (ES+): 514[M+H]TR [HPLC, Phenomenex Luna 3 micron C18; 5-95% CH3CN+0.1%Formic acid/H2O+0.1%Formic acid for 5 min, flow 2.0 ml/min]: 3.57min

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 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine.

Reference:
Patent; NOVARTIS AG; WO2008/77597; (2008); 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. 5049-61-6 name is Pyrazin-2-amine, 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. 5049-61-6

Preparation c-119 5-Bromo-pyrazin-2-ylamine To a solution of pyrazin-2-ylamine (2.0 g, 21.03 mmol) in dry dichloromethane (120 mL) at 0 C., was added N-bromosuccinimide (3.74 g, 21.03 mmol) slowly to maintain the internal temperature below 0 C. The mixture was stirred at the same temperature for 24 hours, and then washed with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The combined aqueous extracts were extracted with dichloromethane (3*100 mL). The combined organic extracts were. dried (anhydrous magnesium sulfate), filtered, and concentrated in vacuo to afford the crude product. The residue was purified by flash column chromatography (10% to 50% ethyl acetate/hexanes) to yield the title compound (2.57 g, 70%) as a yellow solid. LRMS (m/z): 174 (M)-. 1H NMR (CDCl3, 300 MHz): delta 8.08 (1H, d, J=1,3 Hz), 7.76 (1H, d, J=1,3 Hz).

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

Reference:
Patent; Pfizer Inc; US2005/187266; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 95-58-9, name is 2-Chloro-3-methylpyrazine, 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 95-58-9. 95-58-9

Compound 1 (500 g, 1.92 mol) and aqueous ammonia (5.5 L) were placed in a 10 L autoclave and reacted at 160 C for 24 hours. TLC or LCMS showed the reaction was completed.The reaction was cooled and filtered to give a white solid, the remaining reaction solution was extracted with ethyl acetate (1.5 L x 5), the extracts were combined, dried over anhydrous sodium sulfate,The resulting white solid was concentrated under reduced pressure and combined with the filtered solid which was dried in vacuo to give crude compound 2 (420 g).

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 2-Chloro-3-methylpyrazine.

Reference:
Patent; Shanghai He Quan Pharmaceutical Co., Ltd.; Shanghai He Quan Pharmaceutical Research And Development Co., Ltd.; Changzhou Hequan Pharmaceutical Co., Ltd.; Changzhou Hequan Drug Discovery Co., Ltd.; Wuxi Yaoming Kant, Immanuel Pharmaceutical Co., Ltd.; Wuxi Yaoming Kant, Immanuel Bio-technology Co., Ltd.; Mao Yanjun; Tang Xiaowu; Guo Zemin; He Mina; Jiang Xinxin; Bao Weize; Wu Dongping; Yuan Chaowei; Li Hong; Yu Lingbo; Ma Rujian; (5 pag.)CN107312007; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 24241-18-7

To a solution of 3,5-dibromopyrazin-2-amine (40.0 g, 158 mmol), TEA (66.1 mL, 475 mmol), and copper(I) iodide (0.301 g, 1.58 mmol) in THF (1172 ml) was added PdCl2(PPh3)2 (1.11 g, 1.58 mmol). The reaction mixture was cooled at about 0 C. and a solution of (trimethylsilyl)acetylene (20.8 mL, 150 mmol) in THF (146 mL) was added drop-wise. The reaction mixture was stirred at about 0-10 C. for about 7 h and then concentrated under reduced pressure. The dark brown residue was dissolved in DCM (600 mL) and filtered through a Celite pad (3 cm in height¡Á9 cm in diameter) while eluting with DCM (300 mL). The filtrate was washed with water (2¡Á500 mL) and brine (500 mL), dried over anhydrous MgSO4, filtered through a Florisil pad (1 cm in height by 9 cm in diameter) while washing with DCM/MeOH (9:1, 200 mL), and concentrated under reduced pressure to give a brown solid. The solid was triturated and sonicated with warm petroleum ether (b.p. 30-60 C., 250 mL), cooled and collected, washing with petroleum ether (b.p. 30-60 C.; 2¡Á100 mL), and dried in a vacuum oven at about 70 C. to give 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (34.6 g, 70%): LC/MS (Table 2, Method d) Rt=1.59 min; MS m/z: 272 (M+H)+.

The synthetic route of 24241-18-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBOTT LABORATORIES; US2009/312338; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

20737-42-2, 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.

Example 6. Production of N-{3-isobutyl-4-[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]pheny}-3-chloropyrazine-2-carboxamide (compound No. 1-25) 3-Hydroxypyrazine-2-carboxylic acid (154 mg, 1.1 mmol) was dissolved in phosphorus oxychloride (2 ml), followed by adding one drop of pyridine, refluxing under heating for 2 hours. After that, the reaction solution was concentrated under reduced pressure to obtain 3-chloropyrazine-2-carboxylic acid chloride. The compound was added to a tetrahydrofuran solution (10 ml) of 3-isobutyl-4-[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]aniline (299 mg, 1 mmol) and triethylamine (303 mg, 3 mmol) and refluxed under heating for 3 hours. The reaction solution was diluted with ethyl acetate, followed by washing with water. The organic layer was dried over magnesium sulfate anhydride, and concentrated under reduced pressure, and then the residue was purified by using silica gel chromatography (hexane:ethyl acetate=2:1) to obtain 200 mg of the desired compound. Yield: 46% Property: Melting point 128 to 129C

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; NIHON NOHYAKU CO., LTD.; EP1757595; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5521-58-4, Name is 5-Methylpyrazin-2-amine, 5521-58-4, 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.

To a clean dry flask was added 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1.0 mol eq), tetrabutylammonium chloride (0.01 eq), and toluene (10 L/kg). Thionyl chloride (1.5 eq) was added in one go and the reaction heated to 60 C. for 2 hours. The reaction mixture was distilled to an oil at 40 C. on the rotary evaporator, and acetonitrile (4 L/kg) added.To a second clean dry flask was added 5-methylpyrazine-2-amine (1.0 mol eq), pyridine (3.0 mol eq) and acetonitrile (4 L/kg). The acid chloride solution was added to the amine solution over 30 minutes at 22 C. and then allowed to agitate overnight.The reaction mixture was distilled to an oil at 40 C. on the rotary evaporator, and toluene (4 L/kg) added. The reaction mixture was distilled to give an oil at 40 C. on the rotary evaporator, then toluene (10 L/kg added) followed by water (4 L/kg) and 1.0M hydrochloric acid (4 L/kg). The reaction mixture was agitated at 22 C. for 30 minutes, whereupon it crystallized, and toluene (4 L/kg) and water (4 L/kg) was added.The reaction mixture was filtered and washed sequentially with water 2¡Á(2 L/kg), then toluene 2¡Á(2 L/kg).The filtrate was agitated overnight at 22 C. and further crystallisation was observed. The reaction mixture was filtered. The solids were dried to give the title compound as an off-white solid in 35% yield.1H NMR delta (400 MHz DMSO) 10.86 (bs, 1H), 9.75 (bs, 1H), 9.25-9.24 (s, 1H), 9.35 (s, 1H), 6.99 (t, 1H), 6.81 (t, 1H), 6.53-6.52 (t, 1H), 4.72-4.65 (m, 1H), 3.52-3.43 (m, 2H), 3.30 (s, 3H), 2.48 (s, 3H), 1.24-1.22 (d, 3H).

Statistics shows that 5-Methylpyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 5521-58-4.

Reference:
Patent; AstraZeneca AB; US2010/210841; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem