Pyrazines

Some common heterocyclic compound, 27398-39-6, name is 3-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. category: Pyrazines

To a solution of 3-.chioropyrazine-.2-carboxyiic acid (100 mg, 0.63 mmoi) in DCM/MeOFI (2 mL : ().2 mL) was added TMSCHN2 (0.47 mL, 0.95 mmoi) at RT and the resulting mixture stirred at RT for 2 h. Acetic acid (0.2 mL) was added and the mixture diluted with water (2 mL) and extracted with DCM (4 mL x 3). The combined organic layers werewashed with brine, dried over Na2 SO4, filtered and concentrated in vacuo to give the title compound (100 mg) as a colorless oil. LRMS mIz (M+H) 173.0 found, 173.0 required. Step 2: Methyl 3-.pyridin-.2-.yl)pyrazine-2–carboxyiate (M2)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 27398-39-6, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Doug C.; MENG, Na; LUO, Yunfu; (127 pag.)WO2016/101119; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 875781-43-4, 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. 875781-43-4 name is 2-Bromo-5H-pyrrolo[2,3-b]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.

The compound prepared in Example 1 (1.26 mg, 0.3 mm), 5-bromo-1 H-pyrrolo [2,3-b] pyrazine (5 9 (63 mg ‘0.006m m o 1), C u I (1 8 mg, 0.09 mm omicron 1), m m L Epsilon13 Nu and 5 m LD Mu F The reaction was stirred at 80 C for 8 hours under inert atmosphere. The end of the reaction was extracted with ethyl acetate and water. The combined organic layers were washed with a saturated NaC1 solution and dried over anhydrous N ^ SOi. Concentrated under reduced pressure, and the residue was purified on a silica gel column to give the compound as an off-white solid. & Lt; 1 & gt; H NMR (500 MHz, CDC13) delta: 8_91 Page 27 of 53

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; NANJING SHENGHE PHARMACEUTICAL CO., LTD.; WANG, YONG; ZHAO, LIWEN; LIU, YANG; ZHANG, JINGZHONG; WANG, DEZHONG; GAO, YIPING; CHEN, HONGYAN; ZHANG, CANG; ZHANG, DI; (68 pag.)TWI523856; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 912773-21-8, name is 2-Bromo-5-chloropyrazine, 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 912773-21-8, name: 2-Bromo-5-chloropyrazine

To a suspension of copper(O) powder (244 g, 3877 mmol) in DMSO (5 L) was added ethyl 2-bromo-2,2-difluoroacetate (394 g, 1939 mmol) at room temperature. The reaction mixture was stirred at room temperature for 1 hour and 2-bromo-5-chloropyrazine (Shanghai Fchemicals Technology Co., Ltd., Shanghai, China) (250 g, 1292 mmol) was added in a portion-wise manner. The reaction mixture was stirred at room temperature for 3 hours then quenched with sat’d aqueous ammonia chloride (2.0 L). The mixture was filtered through a celite pad and the filtrate was extracted with ethyl acetate (2 x 2 L). The combined organic layers were dried over Na2SC>4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0 to 2% ethyl acetate in hexanes) to afford 3a (215 g, 70% yield) as a viscous colorless liquid. NMR (400 MHz, DMSO-t/6) delta 9.05 (d, J= 1.4 Hz, 1H), 8.98 (dd, J= 1.4, 0.7 Hz, 1H), 4.39 – 4.34 (m, 2H), 1.24 (t, J = 7.1 Hz, 3H).

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

Reference:
Patent; AMGEN INC.; BOURBEAU, Matthew P.; HARRINGTON, Paul E.; LIU, Qingyian; (85 pag.)WO2018/112083; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 41110-29-6, name is Methyl 3-methylpyrazine-2-carboxylate, molecular formula is C7H8N2O2, 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. Quality Control of Methyl 3-methylpyrazine-2-carboxylate

Example 9. Production of methyl 3-chloromethyl-pyrazine-2-carboxylate (compound No. 3-1) Methyl 3-methylpyrazine-2-carboxylate (2.44 g, 16 mmol) was dissolved in chloroform (100 ml) and N-chlorosuccinimde (2.14 g, 16 mmol) was added thereto. Then, benzoyl peroxide (110 mg, 70%, 0.32 mmol) was added and refluxed under heating for 30 hours. The reaction solution was cooled, followed by removing undissolved substance by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by using silica gel chromatography (hexane:ethyl acetate=1:1)to obtain 1.55 g of the desired compound. Yield: 52% Property: 1H-NMR [CDCl3/TMS, delta (ppm)] 8.75(d,1H), 8.68(d,1H), 5.14(s,2H), 4.06 (s,3H),

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 41110-29-6, its application will become more common.

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

Application of 1458-18-0, A common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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.

PREPARATIVE EXAMPLES Preparative Exam ple1.A 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 to8O0C. After 12 hours, the reaction was cooled, diluted with methylene chloride (~ 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 chromatography using a methanol/ methylene chloride eluent (3% to 10% MeOH) to afford 30.8 g (91 %) of compound A3. MS, M+H = 300.

The synthetic route of 1458-18-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SCHERING CORPORATION; PHARMACOPEIA DRUG DISCOVERY, INC.; WO2006/91428; (2006); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine, 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 69214-33-1, COA of Formula: C6H4ClN3

To a stirred solution of the product from step 5 (51 .3 mg, 0.1 7 mmol) in THF (5 mL) was added NaH (20.4 tug, 0.51 mmol, 6() wt% in oil) at 0 C. The mixture was stirred at 0 C for0.5 hour, then 8chioroin:iidazo[i,2a]pyrazine (78.() mg, 0.51 mmoi) was added. The resulting mixture was stirred at RT for 2 hours arid then quenched with water (2 n:iL), extracted with EtOAc (3 x 5 mL). The combined organic layer was wished with brine, dried over Na2SO4, filtered and concentrated in vacuo, and the residue was purified by PrepHPLC to give title compound (28.6 mg) as colorless oil. LRIVIS mlz (M+H) 420.2 found, 420.2 required.

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; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Doug C.; MENG, Na; LUO, Yunfu; (127 pag.)WO2016/101119; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 24241-18-7, 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.

Step A: Preparation of ethyl 6,8-dibromoimidazo[ 1 , 2-a]pyrazine-2-carboxylateTo a stirred solution of 2-amino-3, 5-dibrompyrazine (20 g, 79mmol) in dimethyicarbonate (1 33 mL) at rt was added ethyl 3-bromo-2-oxopropanoate (17.14 g, 79 mmol) in one portion. After stirring at 1 10 C for 3 h, the solution was stirred at rt overnight. Water and DCM were added and the aqueous phase was extracted with DCM. After washing of the organic phase with water, drying over Na2(S04) and filtration the organic phase was evaporated. Flash chromatography yielded 13.95 g (50.6 %) ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate: 1H-NMR (300 MHz, CDC ): delta =8.30 (s, 1 H), 8.27 (s, 1 H), 4.48 (q, 2H), 1 .43 (tr, 3H) ppm.

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

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80228; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 89123-58-0, 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. 89123-58-0, name is 5-Bromopyrazine-2,3-diamine, This compound has unique chemical properties. The synthetic route is as follows.

Step 1 : 6-Bromo-2-(2-cyclopropylpyrimidin-4-yl)-1 /-/-imidazo[4,5-b]pyrazine A mixture of 5-bromopyrazine-2,3-diamine (50 mg, 0.3 mmol) and ethyl 2- cyclopropylpyrimidine-4-carbimidate (Intermediate 19, 50.7 mg, 0.3 mmol), triethylamine (73.8 muIota_, 0.5 mmol), acetic acid (244 muIota_, 4.2 mmol) and ethanol (0.8 mL) was heated to 100C for 30 min. The mixture was concentrated and diluted with water. Then a saturated aqueous solution of sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The organics were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified via flash chromatography (0-5% methanol in dichloromethane) to afford 6-bromo-2-(2- cyclopropylpyrimidin-4-yl)-1 H-imidazo[4,5-b]pyrazine (21 mg, 25%).

The chemical industry reduces the impact on the environment during synthesis 5-Bromopyrazine-2,3-diamine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; PFIZER INC.; AHN, Kay; BOEHM, Markus; CABRAL, Shawn; CARPINO, Philip A.; FUTATSUGI, Kentaro; HEPWORTH, David; KUNG, Daniel W.; ORR, Suvi; WANG, Jian; WO2013/150416; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 33332-28-4, These common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, 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.

The 2-[2-(2,2,2-trifluoroethyl)guanidino]-2-(2-aminoethylthio)pyrazine used as starting material may be obtained as follows: A solution of 2-amino-6-chloropyrazine (1 g.) in warm acetonitrile (15 ml.) was cooled to room temperature. Trifluoroethylisothiocyanate (1.6 g.) was added and the mixture stirred overnight. Further trifluoroethylisothiocyanate (1.6 g.) was added, and the mixture warmed gently on a steam bath for 2 hours, then heated under reflux for 2 hours. The mixture was allowed to cool and evaporated to dryness to yield a brown solid. This was washed with water, 2 N HCl solution, water again, and sucked dry. Recrystallisation from boiling toluene diluted with petroleum ether (b.p. 60°-80°) yielded colourless needles (0.77 g.) of 2-[3-(2,2,2-trifluoroethyl)thioureido]-6-chloropyrazine m.p. 170°-172°.

Statistics shows that 2-Amino-6-chloropyrazine is playing an increasingly important role. we look forward to future research findings about 33332-28-4.

Reference:
Patent; ICI Americas Inc.; Imperial Chemical Industries Ltd.; US4362728; (1982); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 32111-21-0,Some common heterocyclic compound, 32111-21-0, name is 2-Iodopyrazine, molecular formula is C4H3IN2, 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.

Example 58; N- f 3-[” 1 -(4-Chloro-phenvU-6-oxo-2-( 4-pyrazin-2-yl-phenylV 1.6-dihvdro-purin-9-yll-phenyl – methane sulfonamide; [00193] A solution of N-(3-{l-(4-chloro-phenyl)-6-oxo-2-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-l,6-dihydro-purin-9-yl}-phenyl)-methane sulfonamide (preparaed as described in example 26, 0.5 g, 0.809 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (0.25 g, 1.21 tnmol), cesium carbonate (0.527 g, 1.61 mmol), Pd(dppf)2Cl2 (0.059 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is stirred at rt for 18 h. The reaction mixture is poured into water and extracted with ethyl acetate (3 *). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford N-{3-[l-(4-chloro-phenyl)-6-oxo-2-(4-pyrazin-2-yl-phenyl)-l ,6- dihydro-purin-9-yl]-phenyl}-methane sulfonamide. 1H NMR (DMSOd6, 400 MHz) delta 9.25 (s, IH), 8.69 (m, IH), 8.62 (m, 2H), 8.03 (m, 2H), 7.74 (s, IH), 7.46-7.56 (m, 9H), 7.25 (m, IH), 3.05 (s, 3H); LC-MS calculated for C28H20ClN7O3S (M+H4) 570.1, found 569.9.

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

Reference:
Patent; IRM LLC; WO2007/120454; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem