Tag: M.W=100-200

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

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. 3149-28-8, name is 2-Methoxypyrazine, A new synthetic method of this compound is introduced below., 3149-28-8

First, in a three-neck flask, 11.30 g of 2-methoxypyrazine and 200 mL of diethylether were put, and a dibutyl ether solution (2.1 mol/L) of phenyl lithium was dropped thereto while the mixture was cooled down with ices and stirred under a nitrogen atmosphere, and stirred to be reacted for 20 hours. After the reaction, water was added to the reaction solution, and an organic layer was extracted with ethyl acetate. The obtained organic layer was washed with water, and dried with magnesium sulfate. Magnesium sulfate was removed by filtration and the solvent was distilled off. The obtained residue was refined with a column chromatography using dichloromethane as a development solvent, so that 2-phenyl-3-methoxypyrazine was obtained (light yellow powder, yield: 12%).

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; Semiconductor Energy Labratory Co., Ltd.; US2008/312437; (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. 5521-58-4, name is 5-Methylpyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., 5521-58-4

[0386] A mixture of 5-methylpyrazine-2-carboxylic acid (2.76 g, 20 mmol) and oxalyl chloride (1.83 mL, 2.66 g, 21 mmol) in methylene chloride (40 mL) was treated with N,N-dimethylformamide (0.5 mL), and the mixture was stirred at 25 C. for 1 h. The mixture was filtered, and the filtrate was concentrated in vacuo to give an oily solid. The solid was dissolved in acetone (120 mL) at 0 C. and then sodium azide (1.03g, 20 mmol) in water (50 mL) was added dropwise. After the addition was complete, stirring was continued at 0 C. for 30 min. The mixture was then poured into ice cold water (100 mL) and extracted with methylene chloride (3¡Á100 mL). The combined organic extracts were washed with water (1¡Á100 mL), a mixture of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution (1:1, 1¡Á100 mL), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo to give 5-methyl-pyrazine-2-carbonyl azide (1.46 g, 45%) as a tan solid. The 5-methyl-pyrazine-2-carbonyl azide (500 mg, 3.07 mmol) was combined with benzyl alcohol (0.63 mL, 663 mg, 6.14 mmol) at 25 C. The mixture was then slowly heated on an oil bath to 90 C., upon which gas was violently evolved. The oil bath temperature was maintained until gas evolution ceased. The oil bath temperature was raised to 120 C. and stirring was continued for 10 min at that temperature. The mixture was cooled and triturated with diethyl ether/hexanes (1:4) to give (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (438 mg, 58%) as a yellow solid. The (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (500 mg, 2.2 mmol) and 10% palladium on carbon (212 mg) were mixed in ethanol (30 mL). The reaction vessel was flushed with hydrogen, and the mixture was stirred at 25 C. for 1 h under hydrogen (1 atm). The excess hydrogen was evacuated from the reaction vessel, and the mixture was filtered through a pad of celite. Concentration of the filtrate in vacuo gave 2-amino-5-methylpyrazine (183 mg, 76%) as a tan solid which was used without further purification. [0387] A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionic acid (prepared as in Example 60, 263 mg, 0.73 mmol) and triphenylphosphine (250 mg, 0.95 mmol) in methylene chloride (5.0 mL) cooled to 0 C. was treated with N-bromosuccinimide (167 mg, 0.95 mmol) in small portions. After the complete addition of N-bromosuccinimide, the reaction mixture was allowed to warm to 25 C. over 30 min. The bright orange reaction mixture was then treated with 2-amino-5-methylpyrazine (160 mg, 1.46 mmol) and 2,6-lutidine (0.36 mL, 2.92 mmol). The resulting reaction mixture was stirred at 25 C. for 4 h. The reaction mixture was then diluted with methylene chloride (25 mL) and was successively washed with a 10% aqueous hydrochloric acid solution (1¡Á20 mL), a saturated aqueous sodium bicarbonate solution (1¡Á20 mL) and water (1¡Á20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 hexanes/ethyl acetate to 3/7 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-methyl-pyrazin-2-yl)-3-(4-oxo-cyclohexyl)-propionamide (158 mg, 48%) as a white foam: [alpha]23589=-41.52 (c=0.33, chloroform); EI-HRMS m/e calcd for C20H21Cl2N3O4S (M+H)+ 450.1249, found 450.1253.

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; Corbett, Wendy Lea; Grimsby, Joseph Samuel; Haynes, Nancy-Ellen; Kester, Robert Francis; Mahaney, Paige Erin; Racha, Jagdish Kumar; Sarabu, Ramakanth; Wang, Ka; US2003/225283; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, 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. 33332-29-5 name is 2-Amino-5-chloropyrazine, 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.

General procedure: A magnetically stirred solution of xanthate (2.0 equiv) and pyrazine (1.0 equiv) in 1, 2-dichloroethane (1.0mmol/mL according to the xanthate) was refluxed for 15min under a flow of nitrogen. Then dilauroyl peroxide (DLP) was added portionwise (20mol % according to the xanthate) every hour until total consumption of one substrate. The reaction mixture was then cooled to room temperature and the solvent was evaporated under reduced pressure. Unless otherwise specified, the crude product was purified by flash chromatography on silica gel.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-5-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Article; Huang, Qi; Qin, Ling; Zard, Samir Z.; Tetrahedron; vol. 74; 40; (2018); p. 5804 – 5817;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1,Some common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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.

5-(Cyclopropylmethoxy)pyrazine-2-carboxylic acid A solution of 5-chloropyrazine-2-carboxylic acid (1.00 g, 6.31 mmol), cyclopropyl carbinol (1.00 mL, 12.4 mmol) and potassium tert-butoxide (2.00 g, 17.8 mmol) in dimethylformamide (20.0 mL) is heated at 100 C. for 3 hours. The reaction is cooled to room temperature, quenched with 1M hydrochloric acid. The mixture is extracted with ethyl acetate and isopropyl alcohol/chloroform (1/10), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (1.10 g, 90%) as a grayish solid. This acid is used directly without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Chloropyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; GREEN, Steven James; HEMBRE, Erik James; MERGOTT, Dustin James; SHI, Yuan; WATSON, Brian Morgan; WINNEROSKI, JR., Leonard Larry; US2014/371212; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19745-07-4, 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 19745-07-4 as follows.

3.0 g of 2,5-dichloropyrazine,880 mg of sodium hydride (60percent, oil)And 50 mL of NMP,2.3 g of benzyl alcohol was added under ice cooling.The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 5 hours.Water was added to the resulting reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate,And concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography,3.1 g of Intermediate 1 represented by the following formula was obtained.Intermediate 1

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

Reference:
Patent; SUMITOMO CHEMICAL COMPANY LIMITED; SAKAMOTO, EMIKO; NISHIMURA, SHINYA; (242 pag.)JP2018/24669; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 19745-07-4, name is 2,5-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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. 19745-07-4

To a solution of NaH (0.755 g> 18.88 mmol) in THF (55 mL) was added benzyl mercaptan (1.5 mL, 12.68 mmol) at o ¡ãC. The reaction mixture was diluted with THF (20 mL) and stirred at o ¡ãC for 10 minutes. Then a solution of 2,5-dichloropyrazine (1.370 mL, 13.42 mmol) in THF (10 mL) was added dropwise. The reaction mixture was stirred at o ¡ãC for 1 hour, then warmed to room temperature and stirred for 16 hours. The reaction mixture was cooled to o ¡ãC, MeOH (1 mL) was added carefully and stirred for 5 minutes. Water (20 mL), then DCM (150 mL) was added and the biphasic mixture was passed through a phase separator. The organic phase was concentrated in vacuo. The crude product was purified by chromatography on silica gel (40 g column, 0-3percent EtOAc/isohexane) to afford the title compound (2.373 g, 72 percent) as a clear yellow oil. NMR (DMSO-d6) delta 8.68 (d, J = 1.5 Hz, lH), 8.49 (d, J = 1.5 Hz, lH), 7.43 – 7.39 (m, 2H), 7.34 – 7.29 (m, 2H), 7.28 – 7.23 (m, lH), 4.46 (s, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19745-07-4, its application will become more common.

Reference:
Patent; INFLAZOME LIMITED; COOPER, Matthew; MILLER, David; MACLEOD, Angus; VAN WILTENBURG, Jimmy; THOM, Stephen; ST-GALLAY, Stephen; SHANNON, Jonathan; (352 pag.)WO2019/8025; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

3149-28-8, Adding some certain compound to certain chemical reactions, such as: 3149-28-8, name is 2-Methoxypyrazine, 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 3149-28-8.

To a solution of 2-methoxypyrazine (5.0g, 45.4mmol), in 40ml of anhydrous THF was added tributyltin hydride (15.0mL, 54.9mmol) and the resulting solution stirred under nitrogen at 0C. Cyclohexylcarbonyl chloride (8.0mL, 59.8mmol) was added over 10min and stirring continued until reaction completion in 20min as determined by TLC (neutral alumina, EtOAc/hexanes (1/19, v/v)). A 1M solution of HCl in methanol (20.0mL) was then added to the reaction mixture that was stirred under nitrogen at 0C until reaction completion in 30min as determined by TLC (SiO2, EtOAc/hexanes (2/3, v/v). The reaction mixture was quenched with 50mL of water, extracted with ethyl acetate (3¡Á50mL), washed with saturated sodium bicarbonate (10mL), and then dried over anhydrous Na2SO4. Purification by silica gel flash column chromatography (100% hexanes: to remove tin by-products, followed by methanol / dichloromethane 2-5%) afforded 4-cyclohexanecarbonyl-1,2-dihydro-2-pyrazinone 3 (8.9g, 94%) as a pale yellow solid (mp 160-163C dec).

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 3149-28-8.

Reference:
Article; Williams, Alfred L.; St. Hilaire, Valentine R.; Tetrahedron; vol. 73; 48; (2017); p. 6712 – 6717;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common heterocyclic compound, 873-42-7, name is 2-Amino-3,5-dichloropyrazine, molecular formula is C4H3Cl2N3, 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. 873-42-7.

Into a flask, under an inert atmosphere of nitrogen, was placed 1,1,1,2,2-pentafluoro-4-iodobutane (21.7 g, 79 mmol), zinc metal (8.4 g, 128 mmol) and DMA (60 mL). This was followed by the dropwise addition of a solution of iodine (0.77 g, 3.05 mmol) in DMA (4 mL). The resulting mixture was stirred for 3 h at 80C. The reaction was cooled and directly used in the next step. In a flask, under an inert atmosphere of argon, was added 3,5-dichloropyrazin-2-amine (10.0 g, 61.0 mmol) and Pd(PPh3)2Cl2 (4.3 g, 6.1 mmol). The resulting mixture was allowed to stir for 1 h at RT. The intermediate from Step A (65 mL, 79 mmol) was added and the resulting solution was warmed at 45C for 3 h. The reaction was then quenched by the addition of sat. aq. NH4Cl. The resulting solution was extracted with EtOAc (3X), and the organic layers combined, washed with brine, dried over anhydr. Na2SO4, and filtered. The filtrate was conc. in vacuo to dryness. The residue was purified RP-HPLC with acetonitrile:water (0.2% TFA) to afford the title compound.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; BERGER, Raphaelle; DONG, Guizhen; RAGHAVAN, Subharekha; YANG, Zhiqiang; (179 pag.)WO2017/200857; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, Name is 2-Amino-5-chloropyrazine, 33332-29-5, 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.

Step A: S,S-Dimethyl-N-(5-chloropyrazin-2-yl)sulfilimine (5) Compound 5 is prepared from 2-amino-5-chloropyrazine as described above for 2 in Example 1A to afford pure 5 as a smelly, tan solid, m.p. 119-120.

Statistics shows that 2-Amino-5-chloropyrazine is playing an increasingly important role. we look forward to future research findings about 33332-29-5.

Reference:
Patent; Merck & Co., Inc.; US4609659; (1986); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem