Month: April 2021

Synthetic Route of 1458-01-1,Some common heterocyclic compound, 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, molecular formula is C6H7ClN4O2, 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 1A stirred suspension of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester (110 g, 542.9 mmol) in MeOH (500 ml) at 5-10¡ã C. (ice-bath) is treated dropwise with a suspension of lithium hydroxide (46.6 g, benzoyl}benzoyl} mmol) in water (500 ml).The reaction mixture is heated to 50¡ã C. for 5 hours then cooled to room temperature and stirred overnight.The resulting precipitate is collected by filtration and dried in a vacuum oven to afford Lithium 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid as the lithium salt (di-hydrate); [M-Li]- 187.

The synthetic route of 1458-01-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Vertex Pharmaceuticals Incorported; US2011/98311; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 5521-55-1,Some common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, molecular formula is C6H6N2O2, 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.

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 5-methylpyrazine-2-carboxylic acid (1.0 eq), tert-butanol (3.5 vols) and di-isopropylethylamine (1.5 eq) under a nitrogen atmosphere. The mixture was heated to 82 C., then diphenylphosphorylazide (1.0 eq) was added over a time period of 5-14 hours, maintaining the temperature of the reaction mixture at approximately 82 C. The reaction mixture was stirred for at least 1.5 hours, and then cooled to approximately 60 C. A solution of 4% w/w sodium hydroxide (1.75 eq) was added over a period of 2 hours. The mixture was cooled to 15 C. over at least 5 hours then held at 15 C. for 3 hours. The batch was then filtered, and the solid slurry washed with water (2 vols). The batch was again slurry washed with water (2 vols). After drying at 55-60 C. overnight, the desired product was obtained as a solid (corrected yield 56-63%). 1H NMR delta (400 MHz CDCl3): 9.18 (s, 1H), 8.17 (bs, 1H), 8.11 (s, 1H), 2.51 (s, 3H), 1.56 (s, 9H)

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

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

Adding a certain compound to certain chemical reactions, such as: 486424-37-7, name is 3-Amino-6-bromopyrazine-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 486424-37-7, Recommanded Product: 3-Amino-6-bromopyrazine-2-carboxylic acid

HATU (3.54 g, 9.36 mmol) was added to a solution containing 1.64 g (7.5 mmol) of 3-amino-6-bromopyrazine-2-carboxylic acid in 25 mL of DMF. The reaction was stirred for 5 minutes before adding 2.5 mL (22.5 mmol) of N-methylmorpholine and 1.68 g (9.36 mmol) of 4-morpholinopyridin-3-amine. The reaction mixture was stirred for 16 h then quenched with 10 mL of saturated NH4C1 solution and then 10 mL of water. The mixture was extracted with EtOAc three times; the combined organics were washed with brine and then dried over Na2S04. The solvent was then evaporated and the residue was chromatographed (0% to 20% CH3OH / dichloro methane) to afford compound Int lB-1 as a yellow solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Amino-6-bromopyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; SILVERBACK THERAPEUTICS, INC.; THOMPSON, Peter Armstrong; EDRIS, Badreddin; COBURN, Craig Alan; BAUM, Peter Robert; ODEGARD, Valerie; (277 pag.)WO2018/227018; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4744-50-7, 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 4744-50-7 as follows.

3-(5,7-Dimethyl-1,8-naphthyridin-2-yl)carbamoylpyrazine-2-carboxylic acid, m.p. 255 C. with decomposition, can be prepared by reacting pyrazine-2,3-dicarboxylic acid anhydride with 2-amino-5,7-dimethyl-1,8-naphthyridine in anhydrous dimethylformamide at a temperature of about 100 C. 2-Amino-5,7-dimethyl-1,8-naphthyridine, which melts at 225-226 C., can be prepared according to the method of J. Bernstein et al, J. Amer. Chem. Soc., 69, 1151 (1947).

According to the analysis of related databases, 4744-50-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Rhone-Poulenc S.A.; US4016274; (1977); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5049-61-6, These common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, 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.

Sodium nitrite (3.4 g, 50 mmol, 1.3 eq.) was added in small portionsto 98% sulfuric acid (15 mL) ice bath, and the mixture was allowed towarm up and heated to 60. When getting clear, the solution wascooled in an ice bath again. A solution of 2-amino-pyrazine (9) (4 g,39.3 mmol, 1 eq.) in 98% sulfuric acid (15 mL) was added dropwise.The reaction mixture was stirred at 40 for 1 h. After cooling to roomtemperature, it was slowly poured onto crushed ice and stirred until nonitrogen run out. The solution was adjusted to pH 6 with a 40% solutionof sodium hydroxide, resulting in lots of sodium sulfate which wasfiltered off whereafter. The filtrate was extracted with EA (50 mL¡Á3),and the combined organics were dried (Na2SO4), filtered and concentratedin vacuo to give the product as a white precipitate (6.38 g,53%).

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guo, Shuang; Xu, Mingshuo; Guo, Qi; Zhu, Fuqiang; Jiang, Xiangrui; Xie, Yuanchao; Shen, Jingshan; Bioorganic and Medicinal Chemistry; vol. 27; 5; (2019); p. 748 – 759;,
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. 41110-33-2, name is Methyl 5-methylpyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: 41110-33-2

A solution of LAH (164.0 mL, 0.164 mol, 1.0 M in THF, 0.5 equivalents) was added to a suspension of methyl 5-methylpyrazine-2-carboxylate (50 g, 0.328 mol, 1.0 equiv.) in anhydrous THF (750 mL) at -78C. (The internal temperature was kept below -72 C during the addition of LAH). Upon completion of addition, the reaction mixture was left to stir at -78 C for a further 20 min and then quenched with glacial AcOH (50.0 mL) at the same temperature. The resulting mixture was warmed to RT and the volatiles were removed in vacuo. The residue was dissolved in hydrochloric acid (1.5 N, 500 mL) and extracted with DCM (2 x 2 L). The extracts were combined, washed with a saturated aqueous NaHCO3solution (2 x 500 mL), dried over anhydrous Na2SO4, and concentrated in vacuo, to yield the product as a brown oil. The residue was purified by column chromatography (silica gel 60-120 mesh) eluting with a gradient of 10% EtOAc in petroleum ether to provide the title compound as a pale yellow liquid (21.3 g, 53 %). TLC Info: (9.0/1.0 Petroleum ether/EtOAc).1H NMR (400 MHz, CDCl3) delta 10.14 (s, 1H), 9.07 (d, J = 1.5 Hz, 1H), 8.63 (d, J = 1.4 Hz, 1H), and 2.70 (s, 3H). LCMS (ESI positive ion) m/z: 123 (M+H)+.

The synthetic route of 41110-33-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; CHEN, Ning; CHEN, Xiaoqi; CHEN, Yinhong; CHENG, Alan C.; CONNORS, Richard V.; DEIGNAN, Jeffrey; DRANSFIELD, Paul John; DU, Xiaohui; FU, Zice; HARVEY, James S.; HEATH, Julie Anne; HEUMANN, Lars V.; HORNE, Daniel B.; HOUZE, Jonathan; KALLER, Matthew R.; KAYSER, Frank; KHAKOO, Aarif Yusuf; KOPECKY, David J.; LAI, Su-Jen; MA, Zhihua; MEDINA, Julio C.; MIHALIC, Jeffrey T.; NISHIMURA, Nobuko; OLSON, Steven H.; PATTAROPONG, Vatee; SWAMINATH, Gayathri; WANG, Xiaodong; WANSKA, Malgorzata; YANG, Kevin; YEH, Wen-Chen; (700 pag.)WO2018/97945; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)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 1196152-38-1, Safety of 2-Bromo-5-(trifluoromethyl)pyrazine

To a solution of ethyl 2-hydroxyacetate (0.167 mL, 1.762 mmol) in tetrahydrofuran (4 mL) at room temperature was added potassium teri-butoxide (1.850 mL, 1.850 mmol). After 10 minutes, 2-bromo-5-(trifluoromethyl)pyrazine (0.2g, 0.881 mmol) in tetrahydrofuran (4 mL) was added. The mixture was stirred at room temperature overnight. The reaction mixture was quenched by addition of water (10 mL), and extracted with ethyl acetate (3 x 30 mL). The organic phase was dried with MgSO/t, filtered and concentrated under reduced pressure. The residue was used in the next step without further purification (215 mg, 0.859 mmol, 98% yield).JH NMR (400 MHz, DMSO-19F NMR (376 MHz, DMSO- 6) delta ppm -65.37 MS (ESI+) m/z 251 (M+H)+.

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-Bromo-5-(trifluoromethyl)pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; PLIUSHCHEV, Marina, A.; FROST, Jennifer, M.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; XIONG, Zhaoming; SWEIS, Ramzi, Farah; DART, Michael, J.; BROWN, Brian, S.; MURAUSKI, Kathleen; (673 pag.)WO2019/90069; (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. 27825-20-3, name is Methyl 3-Hydroxy-2-pyrazinecarboxylate, A new synthetic method of this compound is introduced below., name: Methyl 3-Hydroxy-2-pyrazinecarboxylate

458 g (3 mol, 1 eq) of methyl 3-hydroxy-2-pyrazinecarboxylate and 532 g (3 mol, 1 eq) Bromosuccinimide were successively added to 5 L of acetonitrile,The mixture was stirred at 25 C for 12 hours,After TLC detection reaction was complete,The reaction was stopped,filter,Filter cake vacuum drying at room temperature,To give 554 g of methyl 6-bromo-3-hydroxy-2-pyrazinecarboxylate (including tautomer 6-bromo-3-oxo-3,4-dihydro-2-pyrazinecarboxylic acid Methyl ester),The yield was 85%. 6-Bromo-3-hydroxy-2-pyrazinecarboxylic acid methyl ester

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; Qingdao Hangdao District Chinese Medicine Hospital; Lu, Yanmin; (5 pag.)CN105732524; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 21943-17-9,Some common heterocyclic compound, 21943-17-9, name is 5-Bromo-3-chloropyrazin-2(1H)-one, molecular formula is C4H2BrClN2O, 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.

General procedure: A solution of 56 (1.50 g, 7.16 mmol), the appropriate secondary amine (8.59 mmol, 1.20 equiv) and diisopropylethylamine (1.50 mL, 8.59 mmol) in n-butanol (15 mL)was heated in a microwave reactor using variable wattage to 140 C for 1 h. The mixture was concentrated and purified by flash column chromatography on silica, eluting with 9:1 dichloromethane/methanol, to give gave 58-63.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-3-chloropyrazin-2(1H)-one, its application will become more common.

Reference:
Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728,16;; ; Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5521-58-4,Some common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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.

Methyl 4-((1-(tert-butoxycarbonyl)piperidin-4-yl)methylamino)-6-chloronicotinate (90 mg, 0.23 mmol), 5-methylpyrazin-2-amine (38 mg, 0.35 mmol, as described in ltoh et al., 2002), cesium carbonate (153 mg, 0.47 mmol), 4,5-bis(diphenyl phosphino)-9,9-dimethylxanthene (11 mg, 8 mol%), and tris(dibenzylidene acetone)dipalladium chloroform complex (10 mg, 4 mol%) were added to an oven-dried microwave reactor vial (2 mL) which was capped and flushed with nitrogen. Anhydrous toluene (1.35 mL) was added and nitrogen was bubbled through the stirred solution for 10 minutes. The mixture was heated at 130C for 30 minutes by microwave irradiation. The solution was cooled, diluted with dichloromethane-methanol and adsorbed onto a 2g lsolute SCX-II column. The resin was washed with methanol, then with 2M ammonia in methanol. The basic fractions were concentrated and the residue was purified by preparative TLC, eluting with 10% methanol – dichloromethane) to give methyl 6-(5- methylpyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)nicotinate (35 mg) as a light green powder.LCMS (3) Rt 3.62 min; m/z (ESI+) 457 (MH+).The material was dissolved in dichloromethane (1mL) at 0C and trifluoroacetic acid (8 drops) was added. The temperature was allowed to rise to ambient. After 2.5 hours the mixture was adsorbed onto a 2g lsolute SCX-II column. The resin was washed with methanol, then with 2M ammonia in methanol. The basic fractions were concentrated. Preparative TLC, eluting with 1 % concentrated ammonia – 10% methanol – 89% dichloromethane, gave methyl 6-(5-methylpyrazin-2-ylamino)-4-(piperidin-4- ylmethylamino)nicotinate (18 mg, 22% over 2 steps) as a yellow powder.1H NMR (500 MHz, DMSO) delta 1.17-1.24 (2H, m), 1.66 (2H, d, J = 12 Hz), 1.68-1.79 (1 H, m), 2.40 (3H, s), 2.48 (2H, t, J = 12 Hz), 2.98 (2H, d, J = 12 Hz), 3.09 (2H, t, J = 6 Hz), 3.22 (1H, t, J = 6 Hz), 3.80 (3H, s), 7.11 (1H, s), 8.00 (1H, t, J = 5.5 Hz), 8.14 (1H, s), 8.54 (1H, s), 8.84 (1H, s), 9.90 (1H, br s). LCMS (3) Rt 1.65 min; m/z (ESI+) 357 (MH+).

The synthetic route of 5521-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; WO2009/44162; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem