Month: January 2021

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. 173253-42-4, name is 2-Amino-5-bromo-6-chloropyrazine, A new synthetic method of this compound is introduced below., name: 2-Amino-5-bromo-6-chloropyrazine

Step 1: 4-(5-amino-3-chloropyrazin-2-yl)benzonitrile A mixture of 5-bromo-6-chloropyrazin-2-amine (1.04 g, 5.00 mmol), (4-cyanophenyl)boronic acid (0.882 g, 6.00 mmol), dichloro(bis{di-tert-butyl[4-(dimethylamino)phenyl]phosphoranyl})palladium (110 mg, 0.15 mmol), sodium carbonate (1.06 g, 10.0 mmol) in 1,4-dioxane (12.0 mL) and water (2.0 mL) was evacuated then filled with nitrogen. The resulting mixture was stirred at 90 C. for 4 h then cooled to room temperature. The mixture was diluted with methylene chloride (15 mL) and water (5 mL). The precipitates were collected by filtration and washed with methyl t-butyl ether then dried to afford the desired product (1.05 g, 91%). LC-MS calculated for C11H8ClN4 (M+H)+: m/z=231.0; found 231.1.

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; Incyte Corporation; Wu, Liangxing; Wang, Xiaozhao; Yao, Wenqing; Zhang, Colin; (38 pag.)US2016/9711; (2016); 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. 59489-71-3, name is 2-Amino-5-bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Amino-5-bromopyrazine

Intermediate 6a: 5-(3-(trifluoromethyl phenyl pyrazin-2-amine.; Into a 500-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 5-bromopyrazin-2-amine (4 g, 22.99 mmol, 1.00 equiv) in 1,4-dioxane (68 mL) and methanol (23 mL), 3-(trifluoromethyl)phenylboronic acid (4.46 g, 23.48 mmol, 1.02 equiv), a solution of sodium carbonate (4.88 g, 46.04 mmol, 2.00 equiv) in water (23 mL), and Pd(PPh3)4 (532 mg, 0.46 mmol, 0.02 equiv). The resulting solution was stirred overnight at 135C in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1 :5). This resulted in 4.4 g (80%) of 5-(3- (trifluoromethyl)phenyl)pyrazin-2-amine as a yellow solid.

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 59489-71-3.

Reference:
Patent; ARDELYX, INC.; LEWIS, Jason, G.; JACOBS, Jeffrey, W.; REICH, Nicholas; LEADBETTER, Michael, R.; BELL, Noah; CHANG, Han-Ting; CHEN, Tao; NAVRE, Marc; CHARMOT, Dominique; CARRERAS, Christopher; LABONTE, Eric; WO2012/6474; (2012); 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. 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, A new synthetic method of this compound is introduced below., Recommanded Product: 136927-64-5

To a mixture of 1 (120 mg, 0.59 mmol) and 2 (90 mg, 0.59 mmol) was added 1.0 ml of Hunig?s base (5.5mmol). The resulting mixture was stirred at 130 C. for 3 h. After the mixture was cooled down to room temperature, 200ml of isopropanol/chloroform (1:2) was added, and the organics were washed with saturated aqueous NaHC03 (2×20 ml)and brine (2×50 ml). The organics were dried over MgSO4 and concentrated under reduced pressure. The residue was purified via flash column chromatography on silica gel (0-10% MeOH in EtOAc) to get the desired product 3 as a brown powder (150 mg, 79%).

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; ChemoCentryx, Inc.; Fan, Junfa; Krasinski, Antoni; Lange, Christopher W.; Lui, Rebecca M.; McMahon, Jeffrey P.; Powers, Jay P.; Zeng, Yibin; Zhang, Penglie; US2014/154179; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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. Product Details of 109838-85-9

To a 100 mL three neck round bottomed flask under nitrogen atmosphere, (R)-2- isopropyl-3,6-dimethoxy -2,5- dihydropyrazine (4 g, 21.7 mmol) was dissolved in dry THF (28 mL) and cooled to -78 C. To this reaction mixture, 1.6 M solution of n-BuLi in hexanes (16.28 mL, 26 mmol) was added dropwise at -78 C and stirred at same temperature for 15 minutes. After 15 minutes, l-bromo-3- (2-bromoethyl)benzene (5.73 g, 21.7 mmol) in dry THF (13 mL) was added dropwise at -78 C and stirred at -78 C for 1 h followed by stirring at room temperature (rt) for 3 h. The reaction was monitored by TLC using ethyl acctatc hcxancs (0.3:9.7) as a mobile phase. After completion of the reaction, reaction mixture was quenched with saturated ammonium chloride solution (75 mL) and extracted using ethyl acetate (3 x 100 mL). Combined organic layer was dried over sodium sulphate and concentrated to give crude which was purified by flash column purification with 1-3 % ethyl acetate in hexanes to yield 3.3 g of (2S,5R)-2-(3-bromophenethyl)-5- isopropyl-3, 6-dimethoxy-2,5-dihydropyrazine (41.38% yield).

The synthetic route of 109838-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PRINCIPIA BIOPHARMA INC.; LOU, Yan; OWENS, Timothy Duncan; BRAMELD, Kenneth Albert; GOLDSTEIN, David Michael; (171 pag.)WO2019/99576; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 33332-28-4,Some common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, molecular formula is C4H4ClN3, 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.

2,6-Dichloropyrazine (2.89 g, 19.4 mmol) was stirred in aqueous NH3 (28%, 10 ml.) and heated to 100C in a sealed tube for 18 hours. The reaction mixture was cooled and the resultant precipitate was filtered. Trituration with water and then ether gave 6- chloropyrazin-2-amine as a white solid (2.28 g, 17.6 mmol, 91 % yield). 1H NMR (d6-DMSO, 400 MHz) ? 6.9 (brs, 2H), 7.70 (d, J = 0.4, 1 H), 7.80 (d, J = 0.4, 1 H); LC-MS (ZQ, 6 minutes) Rt = 1.05 minutes; m/z (ESI+) 130 (M+H).6-Chloropyrazin-2-amine (2.50 g, 19.3 mmol) was stirred in CH2CI2 (60 ml.) at 0C.A/-Bromosuccinimide (2.92 g, 16.4 mmol) was added slowly and the reaction mixture was stirred at 0C for 60 minutes. The reaction mixture was filtered through celite and concentrated to give a brown oil. Purification by flash chromatography, eluting with 0-25% EtOAc-hexanes, gave 5-bromo-6-chloropyrazin-2-amine as a yellow solid (1 .69 g, 8.16 mmol, 42% yield). 1H NMR (de-DMSO, 400 MHz) ? 7.1 (brs, 2H), 7.65 (s, 1 H); LC-MS (ZQ, 4 minutes) Rt = 1.46 minutes; m/z (ESI-) 205 (M-H).A mixture of 5-bromo-6-chloropyrazin-2-amine (1 .00 g, 4.8 mmol), copper (I) iodide (914 mg, 4.8 mmol), 18-crown-6 (95 mg, 0.36 mmol) andtetrakis(triphenylphosphine)palladium (0) (83 mg, 0.072 mmol) was suspended in dry DMF (20 ml.) and a stream of nitrogen was passed through for 5 minutes. Potassium cyanide (312 mg, 4.8 mmol) was added and the mixture was stirred at room temperature for 30 minutes, then refluxed at 200C for 3 hours. The mixture was cooled, diluted with EtOAc and absorbed onto silica gel (10 g). DMF was removed by evaporation. The product was purified by flash chromatography, eluting with 1 :1 EtOAc-hexanes, to yield 5- amino-3-chloropyrazine-2-carbonitrile as a yellow solid (607 mg, 3.93 mmol, 82% yield). 1H NMR (d6 DMSO, 400 MHz) ? 7.87 (s, 1 H), 8.1 (brs, 2H); LC-MS (ZQ, 4 minutes) Rt = 1.20 minutes; m/z (ESI-) 153 (M-H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-6-chloropyrazine, its application will become more common.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; COLLINS, Ian; LAINCHBURY, Michael; MATTHEWS, Thomas Peter; READER, John Charles; WO2013/68755; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 68774-77-6, 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 68774-77-6 as follows.

General procedure: A mixture of chloro compound (50 mg) and amine derivative (2 equiv.) in PEG 400 (2 mL) wasstirred at 120 C for 5 min. After completion the reaction was then cooled to room temperature. DCM and water were added and the phases were separated. The aqueous phase was extracted withDCM and the organic phase was dried and filtered. The removal of solvent gave the product as solid.

According to the analysis of related databases, 68774-77-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Campos, Joana F.; Loubidi, Mohammed; Scherrmann, Marie-Christine; Berteina-Raboin, Sabine; Molecules; vol. 23; 3; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 24241-18-7, These common heterocyclic compound, 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, 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.

Preparation of intermediate 11-1; A solution of product 2-amino-3,5-dibromo-4-ylpyrazine (cas: 117719-17-2), (40 g, 158 mmol, 1.0 eq) in morpholine (41.5 ml, 474 mmol 3.0 eq) was heated at 120C in a parr reactor for 24h. A brown solid appears. The solid was suspended in DCM and washed with Na2C03 aq. sat (twice). The organic phase was dried (MgS04), filtered and solvent removed in vacuo to give a brown solid, which was triturated from Et20 to afford the desired product (30.54 g, 74%) as a pale brown solid as 11-1.

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

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO); PASTOR FERNANDEZ, Joaquin; MARTINEZ GONZALEZ, Sonia; ALVAREZ ESCOBAR, Rosa Maria; RODRIGUEZ HERGUETA, Antonio; MARTIN HERNANDO, Jose Ignacio; RAMOS LIMA, Francisco, Javier; WO2011/89400; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]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 875781-43-4, category: Pyrazines

Step 1-Preparation of 3,5-dimethyl-4-(5H-pyrrolo[2,3-b]pyrazin-2-yl)isoxazole (22): To 2-bromo-5H-pyrrolo[2,3-b]pyrazine (21, 1.36 g, 6.87 mmol) in acetonitrile (51 ml) was added 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (1.87 g, 8.39 mmol), 1M potassium carbonate in water (17 ml), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.2 g, 0.26 mmol) under nitrogen. The reaction was heated at 160 C. in a microwave for 20 minutes. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 0% to 60% ethyl acetate in hexane to give product 22 (1.11 8g, 76%).

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-5H-pyrrolo[2,3-b]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Plexxikon Inc.; Shi, Songyuan; Spevak, Wayne; Zhang, Jiazhong; (84 pag.)US2016/75712; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 89123-58-0, 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. 89123-58-0, name is 5-Bromopyrazine-2,3-diamine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

(b)Add Compound II (7.8 g, 41.3 mmol, 1 eq) to a 250 mL vial and add 80 mL of DMF (ie N,N-dimethylformamide) under constant stirring to dissolve Compound II and add the original Triethyl formate (7.34 g, 49.5 mmol, 1.2 eq) and 20 ml formic acid (about 1 drop/sec)Heating under reflux for 24 h under nitrogen protection(At this time, the TLC test is basically free of raw materials); the solvent is spun off, and methanol is dissolved.Purification by silica gel column chromatography gave 5 g of compound III.

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

Reference:
Patent; Suzhou Derivative Biological Technology Co., Ltd.; Liu Ke; (7 pag.)CN108707150; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 63286-28-2, The chemical industry reduces the impact on the environment during synthesis 63286-28-2, name is 2-Chloro-3-hydrazinylpyrazine, I believe this compound will play a more active role in future production and life.

Reference Example 23-2 Preparation of N’-(3-chloropyrazin-2-yl)-2-ethylpiperidine-1-carbohydrazide racemate To a 100 mL eggplant flask were added 2-ethylpiperidine-1-carbonylchloride (509 mg) prepared in the Reference Example 23-3, diisopropylethylamine (1.11 g), acetonitrile (10 mL), and 2-chloro-3-hydrazinylpyrazine (947 mg) under argon gas flow at room temperature, and the resulting mixture was stirred at 80 C. for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The resulting residues were subjected to silica gel chromatography (hexane:ethyl acetate) using YAMAZEN medium pressure preparative (Silica L (40 g)), the fractions comprising the target compound (Rf value=0.70 (ethyl acetate)) were collected, and concentrated under reduced pressure to give the title compound (332 mg) (yield 36%) as a yellow foam. MS(CI) m/z: 284/286 [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-Chloro-3-hydrazinylpyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MITSUBISHI TANABE PHARMA CORPORATION; UBE INDUSTRIES, LTD.; NAKAJIMA, Tatsuo; HAYASHI, Norimitsu; ISHIZAWA, Kouhei; TSUZAKI, Yasunori; IWAMURA, Ryo; TSUBOIKE, Kazunari; US2019/185479; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem