Category: Pyrazines

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. 74290-67-8, name is 2-Amino-5-bromo-3-methylpyrazine, A new synthetic method of this compound is introduced below., SDS of cas: 74290-67-8

Example 31 N-(3-((5-amino-6-methylpyrazin-2-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-methylbenzenesulfonamide A mixture of 5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-methylbenzenesulfonamide (100 mg), 5-bromo-3-methylpyrazin-2-amine (55 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (14 mg), cesium carbonate (381 mg) and DMSO (2 mL) was stirred under microwave irradiation at 120 C. for 2 hr. After cooling to room temperature, the reaction mixture was filtered through celite, and the filtrate was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and further purified by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)). Fractions containing the object product were collected, neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The obtained organic layer was dried over magnesium sulfate and concentrated to give a residue. The residue was washed with ethyl acetate/IPE/hexane to give the title compound (32 mg). 1H NMR (300 MHz, DMSO-d6) delta 2.29 (3H, s), 2.57 (3H, s), 6.87 (2H, s), 7.13-7.33 (2H, m), 7.47 (1H, d, J=8.1 Hz), 7.58-7.68 (2H, m), 8.04 (1H, s), 10.56 (1H, s).

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 of 109838-85-9, The chemical industry reduces the impact on the environment during synthesis 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, I believe this compound will play a more active role in future production and life.

Preparation 13: [(lS2RV3-arnino-l-(315-Muoro-bemyl)-2-hydroxy-propyl]-carbarnic acid t-butyl ester Step A: (2S,5RV2,5-dihvdro-3,6-dimethoxy-5-isopropyl-2-(3,5-dMuoro)benzylpyrazine(TR.)-2,5-dihydro-3,6-dirnethoxy-2-isopropylpyrazine (9.2 g, 50 mmol) was dissolved in THF (100 mL), to which n-BuLi (4M in THF, 15 mL) was then added at -78 °C, followed by addition of difluorobenzyl chloride (9.72 g, 60 mmol). After the reaction was complete, NH4Cl was added to the reaction mixture which was then extracted with EtOAc. The organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (EtOAc: n-Hex = 1/1) to afford the title compound (12.4 g, 80percent).

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, (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, other downstream synthetic routes, hurry up and to see.

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. 4744-50-7, name is 2,3-Pyrazinecarboxylic anhydride, A new synthetic method of this compound is introduced below., name: 2,3-Pyrazinecarboxylic anhydride

12H-pyrazino[2′,3′:3,4]pyrrolo[1,2-a]perimidin-12-one (1): Naphthalene-1,8-diamine (40 mg, 0.057 mmol), furo[3,4-b]pyrazine-5,7-dione (40 mg, 34 mmol), and 10ml pyridine were added into a round bottom flask and heated to reflux. After 4h, the reaction mixture cooled down and the solvent was removed under reduced pressure. The crude residue was dispersed in 50 mL methanol with strong agitation. After 1h, the solid was collected by vacuum filtration and purified using silica-gel column chromatography with methylene chloride:methanol (50:1) to afford 1 (28 mg, 39%) as a red powder. 1H NMR (CDCl3, 400 MHz) delta 9.06 (d, 2H), 8.67 (d, 1H), 7.65-7.71 m (m, 3H), 7.54-7.57 (m, 2H); FT-IR 1732, 1654, 1402, 1375, 1131, 831, 760, 423 cm-1; Mp > 250oC; MALDI-TOF MS exact mass (M + H): 272.28; calcd. Mass: 271.27.

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:
Article; Zhao, Jian-Feng; Liu, Yi; Soh, Jiayun Bethia; Li, Yong-Xin; Ganguly, Rakesh; Ye, Kai-Qi; Huo, Fengwei; Huang, Ling; Tok, Alfred Iing Yoong; Loo, Joachim Say Chye; Zhang, Qichun; Tetrahedron Letters; vol. 53; 45; (2012); p. 6044 – 6047;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 32710-14-8, A common heterocyclic compound, 32710-14-8, name is 3-Aminopyrazine-2-carbaldehyde, molecular formula is C5H5N3O, 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.

EXAMPLE 77 Pyrido[2,3-b]pyrazine-6,7-dicarboxylic acid, diethyl ester STR163 Diethyl oxalacetate, (4.7 g, 0.025 mol) and piperidine (1.66 g, 1.93 mL) are added to 3-aminopyrazine-2-carboxaldehyde (2.4 g, 0.0195 mol) dissolved in 250 mL of toluene. After the reaction mixture is refluxed for two hours, the toluene is removed under reduced pressure to give a dark red oily residue. The product is purified by column chromatography on silica gel (hexane:EtOAc, 4:1), affording 3.1 g (58% yield), of the crude desired product. Crystallization from ether-hexane (4:1) gives analytically pure compound 1.5 g (28%) having a melting point 83-85 C.

The synthetic route of 32710-14-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; American Cyanamid Company; US5252538; (1993); A;,
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. 19847-12-2, name is Pyrazinecarbonitrile, This compound has unique chemical properties. The synthetic route is as follows., Formula: C5H3N3

2-Cyanopyrazine (1.0g, 9.5mmol) was dissolved in dry methanol (50mL) with stirring at room temperature. Metallic sodium (0.12g, 5.2mmol) was added and the mixture refluxed for 2h. The clear yellow solution of the in situ iminoester was brought to neutral pH with glacial acetic acid resulting in a clear orange solution. 2-(Hydoxyimino)-propanehydrazone [14,15] (1.1g, 9.3mmol) was added and the resulting solution refluxed for 1h, and stirred at room temperature overnight. The white solid formed was separated by suction filtration and washed with methanol and diethylether (Yield: 1.85g, 90%). 1H NMR (300MHz, DMSO-d6, 298K) delta (ppm) 11.72 (s, 1H, N-OH), 10.03 (s, 1H, NH), 9.27 (d, 1H, CH(pyz)), 8.70 (d, 1H, CH(pyz)), 8.64 (dd, 1H, CH(pyz)), 6.99 (s, 2H, NH2), 1.95 (s, 3H, CH3). 13C{1H} NMR (75.4MHz, DMSO-d6, 298K) delta (ppm) 160.52 (C=O), 150.66, 146.14 (C=N), 146.04 (C(pyz)), 145.01, 142.86, 142.72 (CH(pyz)), 10.20 (CH3). Selected IR data (cm-1): 3247 br (nu N-H), 1650 s (nu C=O), 1621 s, (nu C=N), 1045 s (nu N-Ooxime). M. pt. 240-242C.

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 19847-12-2.

Reference:
Article; Drover, Marcus W.; Tandon, Santokh S.; Anwar, Muhammad U.; Shuvaev, Konstantin V.; Dawe, Louise N.; Collins, Julie L.; Thompson, Laurence K.; Polyhedron; vol. 68; (2014); p. 94 – 102;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, molecular formula is C5H2BrF3N2, 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. Product Details of 1196152-38-1

To a suspension of Example 3B (0.08 g, 0.249 mmol) in N,N-dimethylformamide (0.5 mL, 6.46 mmol) were added N,N-diisopropylethylamine (0.174 mL, 0.996 mmol) and 2-bromo- 5-(trifluoromethyl)-pyrazine (0.068 g, 0.299 mmol). The reaction mixture was stirred overnight at 90 C, and then it was concentrate under reduced pressure at 50 C. The residue was purified by flash column chromatography on silica gel (12 g) eluted with heptane and ethyl acetate (0 to 100%) to give 40 mg of the title compound (37.3% yield) as a white solid. JH NMR (400 MHz, DMSO- ) delta ppm 8.78 (s, 1H), 8.59 (s, 1H), 8.44 (s, 1H), 7.99 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.27 (d, J = 2.8 Hz, 1H), 6.99 (dd, J = 9.0, 2.9 Hz, 1H), 4.51 (s, 2H), 2.37 (s, 6H); 19F NMR (376 MHz, DMSO- ) delta ppm -64.83, -114.06; MS (ESI+) m/z 447 (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 1196152-38-1, its application will become more common.

Reference:
Patent; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; FROST, Jennifer, M.; PLIUSHCHEV, Marina, A.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; SWEIS, Ramzi, Farah; DART, Michael, J.; RANDOLPH, John, T.; MURAUSKI, Kathleen; (674 pag.)WO2019/90076; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 33332-29-5, 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 33332-29-5 as follows.

(iii) 2-Amino-5-chloropyrazine (1.7 g) was dissolved in chloroform (190 ml) and pyridine (1.3 ml) was added under an argon atmosphere. The flask and its contents were protected from light and a solution of bromine (0.7 ml) in chloroform (85 ml) was added over a period of 1 hour. After stirring for 2 hours more bromine (0.07 ml) in chloroform (8.5 ml) was added and, after stirring for 30 minutes, pyridine (0.2 ml) was added. The reaction mixture was stirred for a further 30 minutes then washed with water (50 ml) and the organic phase was separated. The solvent was removed by evaporation and the residue was purified by chromatography through a bed of silica (90 g), eluding with hexane (200 ml) followed by dichloromethane. Dichloromethane fractions containing the product were evaporated to give 2-amino-3-bromo-5-chloropyrazine (1.68 g); 1 H NMR (d6 DMSO): 6.94 (br s, 2H), 8.09 (s, 1H); mass spectrum (+ve CI): 208 (M+H)+.

According to the analysis of related databases, 33332-29-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Zeneca Ltd.; US5668137; (1997); A;,
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. 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C5H4Br2N2O

A solution of tert-butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate (2d, 1.7 g, 5.7 mmol, 1 equiv.), 3,5-dibromo-1-methylpyrazin-2(1H)-one (2e, 1.8 g, 6.8 mmol, 1.2 equiv.) and N,N-diisopropylethylamine (1.48 mL, 8.5 mmol, 1.5 equiv.) in N,N-dimethylacetamide (5 mL) was stirred in a sealed vial at 105 oC for 30 h. The reaction was cooled to room temperature and EtOAc (20 mL) was then added. The solid precipitate was filtered and dried on high vacuum overnight to provide tert-butyl 4-(4-((6-bromo-4-methyl-3-oxo-3,4- dihydropyrazin-2-yl)amino)benzoyl)piperazine-1-carboxylate 2f. The product was carried onto the next step without further purification.

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 87486-34-8.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael S.; DOBROVOLSKY, Dennis; HUANG, Hai-Tsang; (182 pag.)WO2018/98288; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 221136-66-9, These common heterocyclic compound, 221136-66-9, name is Ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate, 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.

{6-Methyl-2-oxo-3-[2-(pyridin-2-yloxy)-ethylamino]-2H-pyrazin-1yl}-acetic acid ethyl ester. A solution of 70.0 mg (0.254 mmol) of (3-bromo-6-methyl-2-oxo-2H-pyrazin-1-yl)-acetic acid ethyl ester (for preparation see Synth. Comm.; 30; 2000; 3171-3180) and 85.2 mg (0.560 mmol) of 2-(pyridin-2-yloxy)-ethylamine in 5 mL of ethanol is heated over night at 130 C in a sealed tube. After allowing to cool down, the solution is diluted with 10 mL of water and then extracted three times with ethyl acetate. The organic phase is separated, dried with sodium sulfate and the solvent is removed under reduced pressure. The crude mixture is purified using flash chromatography (silica gel, eluent: 50% ethyl acetate in cyclohexane) to afford 22.0 mg (26%) of the title compound. LC/MS (I) rt 2.40, m/z 333 (M+H).

The synthetic route of 221136-66-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Graffinity Pharmaceuticals Aktiengesellschaft; EP1526131; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 41110-29-6, 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. 41110-29-6 name is Methyl 3-methylpyrazine-2-carboxylate, 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.

A solution of mixture of 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide compound with 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide (1:1) (5.1 g, 15.17 mmol) in toluene (50 mL) was cooled to 0 C. To the mixture was added phosphorus oxychloride (2.78 ml, 30.3 mmol) under nitrogen followed by n,n?-dimethylformamide (0.117 ml, 1.517 mmol). The reaction mixture was stirred at room temperature for 4 h and then was heated to 65 C. for 18 h. The mixture was cooled to room temperature, diluted with EtOAc and washed with saturated NaHCO3 solution. The aqueous layer was back-extracted with EtOAc. The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The mixture was purified with ISCO (0% to 50% EtOAc/Hexanes) to afford both isomers: methyl 5-chloro-3-methylpyrazine-2-carboxylate (0.68 g, 48.1% yield) and methyl 6-chloro-3-methylpyrazine-2-carboxylate (1.5 g, 106% yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-methylpyrazine-2-carboxylate, and friends who are interested can also refer to it.

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