Author: Jessica.F

Synthetic Route of 23611-75-8,Some common heterocyclic compound, 23611-75-8, name is Methyl 6-chloropyrazine-2-carboxylate, molecular formula is C6H5ClN2O2, 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-((2-Chloro-5-nitrobenzyl)oxy)pyrazine-2-carboxamide (IE3) An oven-dried seal tube was charged with Pd(OAc)2 (4.4 mg, 0.02 mmol, 1 mol %), t-Bu-Xphos (17 mg, 0.04 mmol, 2 mol %) and Cs2CO3 (980 mg, 3.0 mmol, 1.5 equiv). The seal tube was sealed with a septum, evacuated and back-filled with argon. Toluene (10 mL), methyl 6-chloro-2-pyrazinecarboxylate (IE2, 340 mg, 2.0 mmol), and 2-chloro-5-nitrobenzyl alcohol (IE1, 1.13 g, 6.0 mmol) were added via syringe. The reaction mixture was heated at 100 C. for 24 h, then cooled to room temperature, diluted with EtOAc (20 mL), filtered through a pad of Celite, and concentrated. The residue was purified by flash column chromatography (0-50% EtOAc/hexanes) to afford an inseparable mixture of IE1 and the coupling product. This mixture in NH3/MeOH (ca. 7 N, 20 mL) in a seal tube was heated at 70 C. for 24 h. After the solvent was evaporated in vacuo, the residue was dissolved in EtOAc (150 mL) and the resulting solution was washed with H2O (150 mL) and brine (100 mL). After the organic layer was dried over Na2SO4 and filtered, the filtrate was concentrated and the residue was purified by flash column chromatography (0-15% MeOH/CH2Cl2) to afford compound IE3 as a light yellow solid (100 mg, 16% over two steps). 1H NMR (CDCl3, 600 MHz) delta 9.06 (s, 1H), 8.60 (s, 1H), 8.47 (d, J=2.4 Hz, 1H), 8.19 (dd, J=9.0, 2.4 Hz, 1H), 7.63 (d, J=9.0 Hz, 1H), 5.59 (s, 2H). HRMS (ESI+) calcd for C12H10ClN4O4 (M+H)+ 309.0385, found 309.0392.

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

Reference:
Patent; REGENTS OF THE UNIVERSITY OF MINNESOTA; Chen, Liqiang; Ai, Teng; More, Swati; (111 pag.)US2016/376238; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 63744-22-9, A common heterocyclic compound, 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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.

[0303] 6-Bromo-N-(4-(4-(oxetan-3-yI)piperazin-1-yl)-3-(2-((tetrahydro-2H- pyran-2 yl)oxy)ethoxy)phenyl)imidazo [1,2-a]pyrazin-8-amine XXV: To a solution of 4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((te1rahydro-2H-pyran-2-yl)oxy)emoxy)aniline XXIV (619 mg, 2.17 mmol) and 6,8-dibromoimidazo[1,2-a]pyrazine (601 mg, 2.2 mmol) in IPA (15 mL) was added N,N-Diisopropylethylamine (0.95 ml, 5.43 mmol). The mixture was stirred at 110 C for 16 h. After this time, DCM (10 mL) and sat aqueous NaHC03 (15 mL) were added. The aqueous layer was separated and extracted with DCM (2 10 mL). The combined organic extracts were washed with brine (10 mL) and dried over sodium sulfate. The resulting residue was purified by column chromatography ISCO Rf (24 g column) eluting with a gradient of 100% DCM – 60:35:5 DCM:Et20:MeOH to provide 6-bromo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)-3- (2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)imidazo[ 1,2-a]pyrazin-8-amine XXV (1.2 g, quant).

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; GILEAD SCIENCES, INC.; BLOMGREN, Peter, A.; CLARKE, Astrid; CURRIE, Kevin, S.; DI PAOLO, Julie; KROPF, Jeffrey, E.; LEE, Seung, H.; LO, Jennifer, R.; MITCHELL, Scott, A.; SCHMITT, Aaron, C.; SWAMINATHAN, Sundaramoorthi; XIONG, Jin-Ming; XU, Jianjun; ZHAO, Zhongdong; (169 pag.)WO2016/10809; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 4774-14-5, name is 2,6-Dichloropyrazine, 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 4774-14-5, name: 2,6-Dichloropyrazine

A solution of compound 8 (450.0 g, 3.02 mol) in cone. aq. NH3 (3.0 L) was stirred at 135¡ãC overnight in a 10 L sealed pressure vessel. TLC and LC/MS showed complete conversion of the starting material. The reaction mixture was cooled to room temperature and filtered to afford a white solid. The solid was washed with water (200 mL x 3), and then dried to afford compound 9 (312 g, 80percent yield) as a solid. 1HNMR (400 MHz, DMSO- 6): delta 7.82 (s, 1 H), 7.12 (s, 1 H), 6.93 (s, 2H). MS Calcd.: 129 MS Found: 130 ([M+H]+).

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; IMARA, INC.; H. LUNDBECK A/S; SVENSTRUP, Niels; PARACHIKOVA, Anna I.; MCARTHUR, James; (133 pag.)WO2018/9424; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 16298-03-6, 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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Example 81; Synthesis of (3,5-bis-trifluoromethyl-benzyl)- [3-(cycIopentylmethyl-ethyl-amino)- pyrazin-2-ylmethyl]-carbamic acid methyl ester; Step (i): Synthesis of 3-bromo-pyrazine-2-carboxylic acid methyl ester; Copper bromide (1.36 g, 6.1 mmol) and ¡ê-butyl nitrite (0.78 g, 7.6 mmol) were added to a 50 mL round bottom flask along with acetonitrile (2 niL), and this mixture was heated at 60 0C for 5 min. After this time, 3-amino-pyrazine-2-carboxylic acid methyl ester (0.8 g, 5.09 mmol) was added portion- wise, with stirring, and stirring was continued at the same temperature for another 10 min. The reaction mixture was then cooled to RT, poured into 100 mL of dilute HCL (2N), and then extracted with diethyl ether (3 x 50 mL). The combined organic layer was washed with dilute HCl, dried over sodium sulfate, and then concentrated under vacuum to afford the title compound (0.139 g), yield: 12 %.1H NMR (CDCl3, 400 MHz): d 8.58 (m, 2H), 4.04 (s, 3H)) ; m/z (CI-MS) 217 (M+) ; IR (neat, cm-1): 3385, 2955, 1742

The synthetic route of Methyl 2-aminopyrazine-3-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; REDDY US THERAPEUTICS, INC.; BARUAH, Anima; DE, Dibyendu; KHANNA, Ish Kumar; PILLARISETTI, Sivaram; MAITRA, Santanu; ALEXANDER, Christopher, W.; SREENU, Jennepalli; DAGER, Indu; WO2006/73973; (2006); 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. 221136-66-9, name is Ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate, A new synthetic method of this compound is introduced below., Computed Properties of C9H11BrN2O3

Step 3 3-(2-Ethylpyrid-3-ylamino)-6-methyl-1-(ethoxycarbonylmethyl)pyrazinone A mixture of 2-ethyl-3-aminopyridine (0.35 g, 2.8 mMol, 2 eq) from step 2 above and 3-bromo-6-methyl-1-(ethoxycarbonylmethyl)pyrazinone (0.39 g, 1.4 mMol) in 1 mL of nitrobenzene was heated at 200 C. for 2 h. The reaction was concentrated in vacuo and the residue purified by flash silica gel chromatography using 1% methanol in methylene chloride as an eluent to afford the title compound as a yellow oil that crystallizes upon sitting. (0.058 g; HPLC RT=4.45 min, method A).

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; Merck & Co., Inc.; US6610692; (2003); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, molecular formula is C7H5ClN2, 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. Application In Synthesis of 1-Chloropyrrolo[1,2-a]pyrazine

To a solution of (5)-tert-butyl pyrrolidin-3-ylcarbamate (0.91 g, 4.9 mmol, 1 eq) in 2.6 mL of DIPEA was added 1-chloropyrrolo[1,2-a]pyrazine (0.75 g, 4.9 mmol, 1 eq) and 1 drop of 1-butyl-3-methylimidazolium tetrafluorborate. After heating for 3 h at 110 C., the mixture was concentrated and purified by silica gel flash chromatography (100% EtOAc) to afford (S)-tert-butyl N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)carbamate (0.88 g, 2.9 mmol, 59%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 136927-64-5, its application will become more common.

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

Synthetic Route of 1082843-72-8, These common heterocyclic compound, 1082843-72-8, name is 6-Bromo-3-chloropyrazin-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.

6-Bromo-3- chloropyrazin-2-amine (2000 mg, 9.59 mmol) was dissolved in DCM (48 ml) followed by triethylamine (3.99 ml, 28.78 mmol), di-tert-butyl dicarbonate (4188. 12 mg, 19.19 mmol), and N,N-dimethylpyridin-4-amine (87.91 mg, 0.72 mmol). The reaction was allowed to stir at room temperature for ovemight. The crude material was washed with water, dried, filtered and concentrated. The crude material was dissolved in minimal DCM and loaded onto a 25 g prepacked silica loader and eluted off a 40 g column using 0-30% MeOH/DCM. The title compound XI was isolated and identified by LCMS and NMR. The product was a mix of mono and bis boc-protected material, mainly bis boc-protected as observed by NMR.

The synthetic route of 1082843-72-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GILEAD SCIENCES, INC.; DI PAOLO, Julie, A.; LIN, Joseph, Haw-Ling; LIN, Shao-Lee; (86 pag.)WO2016/172117; (2016); 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. 91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, A new synthetic method of this compound is introduced below., Safety of 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine

Compound ii-26a (2.38 g, 19.33 mmol) (see US 2008/153843 A1 and others) was dissolved in tetrahydrofuran (95 mL), and thereto was added compound ii-2b (9.50 g, 17.39 mmol). The resultant solution was stirred at room temperature. After the end of the reaction, purified water was added to the reaction liquid. From the water phase, the resultant reaction product was extracted with ethyl acetate. The resultant organic phase was washed with a 5% aqueous sodium hydrogencarbonate solution, purified water, and a saturated salt solution in turn. The organic phase was dried over anhydrous magnesium sulfate, and magnesium sulfate was then removed therefrom by filtration. The solvent was distilled off therefrom under reduced pressure. The resultant residue was subjected to silica gel chromatography to yield compound ii-2 6b (yielded amount: 8.3 g, yield: 80%).1H-NMR (CDCl3) delta: 7.40-7.30 (4H, m), 7.08-6.81 (8H, m), 5.09-4.98 (4H, m), 4.54-4.51 (1H, m), 4.48-4.33 (1H, m), 4.17-3.94 (2H, m), 3.84 (3H, s), 3.80 (3H, s), 3.63-3.45 (1H, m), 1.88-1.60 (1H, m).

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; Shionogi & Co., Ltd.; HISAKAWA, Shinya; HASEGAWA, Yasushi; AOKI, Toshiaki; KUSANO, Hiroki; SANO, Masayuki; SATO, Jun; YAMAWAKI, Kenji; EP2557082; (2013); 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. 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate

General procedure: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

According to the analysis of related databases, 1458-01-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Buckley, Benjamin J.; Majed, Hiwa; Aboelela, Ashraf; Minaei, Elahe; Jiang, Longguang; Fildes, Karen; Cheung, Chen-Yi; Johnson, Darren; Bachovchin, Daniel; Cook, Gregory M.; Huang, Mingdong; Ranson, Marie; Kelso, Michael J.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 24; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 873-42-7, name is 2-Amino-3,5-dichloropyrazine, 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 873-42-7, name: 2-Amino-3,5-dichloropyrazine

Benzyl alcohol (7.60 mL, 73.2 mmol) was added slowly to a stirred suspension of sodium hydride (60% dispersed in mineral oil) (2.95 g, 73.2 mmol) in dry THF (122 mL). The mixture was stirred at rt for 10 min, after which 10 (7.30 g, 44.5 mmol) was added and the mixture was heated at reflux for 24 h. The cooled solution was concentrated, and ethyl acetate (500 mL) and water (200 mL) were added to the resulting gum. The mixture was filtered through Celite. The organic layer was separated, washed with brine (2*100 mL), dried, filtered and concentrated. Flash column chromatography on silica, eluting with 1:1 ethyl acetate/hexanes, gave a solid, which was recrystallised from water (200 mL) to give 11 (6.00 g, 57%) as an orange solid. Mp 285-287 C (from water); Rf (50% EtOAc/hexanes) 0.41; numax (thin film/cm-1) 3409 (NH2), 3019 (Ar CH), 929 (C-O); (found: C, 56.19; H, 4.26; N, 17.65; C11H10N3OCl requires C, 56.06; H, 4.28; N, 17.83%); deltaH (500 MHz; CDCl3) 4.77 (2H, br s, NH2), 5.32 (2H, s, OCH2), 7.30-7.39 (5H, m, Ph), 7.51 (1H, s, 6-H); deltaC (125 MHz; CDCl3) 69.0, 128.5, 128.6, 128.6, 131.7, 131.9, 135.7, 143.8, 146.7; LC-MS (15 min) m/z 236 (MH+) HPLC tR 7.49 min; purity 99% HRMS (found: MH+ m/z 236.0585; requires 236.0585).

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-Amino-3,5-dichloropyrazine, other downstream synthetic routes, hurry up and to see.

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