Month: July 2021

Some common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, molecular formula is C4H2BrIN2, 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

Step 1: 1-(5-Bromo-pyrazin-2-yl)-4,4-dimethyl-pyrrolidin-2-one To a well stirred suspension of 2-bromo-5-iodopyrazine (300 mg, 1.05 mmol), 4,4-dimethylpiperidin-2-one (155 mg, 1.37 mmol, 1.3 equiv.) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos) (24.4 mg, 0.042 mmol, 0.04 equiv.) in 4 ml of toluene were added under argon atmosphere tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), (19.3 mg, 0.021 mmol, 0.02 equiv.) and the mixture was stirred for 5 hours at 100 C. The crude mixture was adsorbed on silicagel and purified by flash chromatography over a 20 g silicagel column using a 2:1 heptane/ethyl acetate mixture as eluant. The title compound (151 mg, 53% yield) was obtained as a white solid, MS: m/e=270.1, 272.1 (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 622392-04-5, its application will become more common.

Reference:
Patent; Green, Luke; Guba, Wolfgang; Jaeschke, Georg; Jolidon, Synese; Lindemann, Lothar; Ricci, Antonio; Rueher, Daniel; Stadler, Heinz; Vieira, Eric; US2011/251169; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5521-58-4, 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. 5521-58-4, name is 5-Methylpyrazin-2-amine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 5-methylpyrazin-2-amine (5.00g, 45.8 mmol) and pyridine (4.35g,55.0 mmol) in DCM (250 mL) was added bromine (8.80 g, 55.0 mmol). The mixture was stirredat rt overnight. To the reaction mixture was added water (150 mL), and the resulting mixture waspartitioned. The organic layer was washed with saturated brine (100 mL), dried over anhydroussodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound asa yellow solid (7.64 g, 88 %).MS (ESI, pos. ion) m/z: 190.2 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 7.83 (s, lH), 4.93 (s, 2H), 2.41 (s, 3H).

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, 5-Methylpyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; TANG, Changhua; REN, Qingyun; YIN, Junjun; YI, Kai; LEI, Yibo; WANG, Yejun; ZHANG, Yingjun; (303 pag.)WO2018/108125; (2018); 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. 41110-29-6, name is Methyl 3-methylpyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C7H8N2O2

A solution of methyl 3-methylpyrazine-2-carboxylate (9.1 g, 59.8 mmol) in DCM (100 mL) was cooled to 0 C. was added urea hydrogen peroxide adduct (7.8 g, 83.0 mmol), followed by dropwise addition of trifluoroacetic acid anhydride (10.8 mL, 78.0 mmol). The resulting mixture was stirred at 0 C. for 1 h, and at RT for 18 h, during which LCMS indicated a mixture of two peaks corresponding to MS m/z=169.0 [M+H]+. The reaction was diluted with DCM and quenched with saturated Na2SO3 solution; the aqueous layer was back-extracted with DCM (2×). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (20-80% EtOAc/hexanes) afforded a mixture of two regioisomers, containing 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide (5.2 g, 30.9 mmol, 51.7% yield). The mixture of regioisomers was taken to next step without further purification. MS m/z=169.0 [M+H]+. A solution of the mixture of 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide (5.1 g, 15.2 mmol) in toluene (50 mL) was cooled to 0 C. and phosphorus oxychloride (2.8 mL, 30.3 mmol) was added under nitrogen followed by DMF (0.12 mL, 1.52 mmol). The reaction mixture was stirred at RT for 4 h, and heated to 65 C. for 18 h, cooled to RT, diluted with EtOAc and washed with saturated NaHCO3 solution. The aqueous layer was back-extracted with EtOAc (2×). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (0-50% EtOAc/hexanes) with care afforded both isomers: methyl 5-chloro-3-methylpyrazine-2-carboxylate (0.68 g) (minor product) denoted by peak 1 and methyl 6-chloro-3-methylpyrazine-2-carboxylate (1.50 g) (major product) denoted by peak 2. MS m/z=187.0 [M+H]+. Peak 1: 1H NMR (300 MHz, DMSO-d6) delta 8.73 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H). Peak 2: 1H NMR (300 MHz, DMSO-d6) delta 8.89 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H).

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; LEWIS, Richard T.; ALLEN, Jennifer R.; BROWN, James; GUZMAN-PEREZ, Angel; HUA, Zihao; JUDD, Ted; LIU, Qingyian; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; US2015/38497; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 5900-13-0, These common heterocyclic compound, 5900-13-0, name is 5-Bromo-3-methoxypyrazin-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.

(ii) 2-Amino-5-bromo-3-methoxypyrazine (0.3 g) was added to a stirred suspension of sodium hydride (60% dispersion in oil; 0.15 g) in dimethoxyethane (5 ml). After 10 minutes, 5-(N-benzyloxycarbonyl-N-methylamino)-1-naphthalenesulphonyl chloride (0.6 g) in dimethoxyethane (2 ml) was added and stirring was continued for 2 hours. The mixture was poured into water (20 ml) and washed with ethyl acetate (20 ml). The aqueous layer was acidified with concentrated hydrochloric acid to pH2 and extracted with ethyl acetate (3*50 ml). The combined organic extracts were dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica gel (25 g), eluding with a gradient of 20-50% ethyl acetate in hexane to give 5-(N-benzyloxycarbonyl-N-methylamino)-N-(5-bromo-3-methoxy-2-pyrazinyl)-1-naphthalenesulphonamide (0.50 g) as a white foam; 1 H NMR (d6 -DHSO): 3.34 (s,3H), 3.90 (s,3H), 5.08 (br,2H), 6.95 (br,1H), 7.19 (br,2H), 7.22-7.56 (m,2H), 7.6-7.77 (m,3H), 7.79 (s,1H), 8.07 (d,1H), 8.37 (dd,1H), 8.80 (d,1H), 11.58 (br,1H); mass spectrum (+ve FAB, DMSO/NBA): 557(M+H)+.

Statistics shows that 5-Bromo-3-methoxypyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 5900-13-0.

Reference:
Patent; Zeneca Limited; US5861401; (1999); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 59303-10-5,Some common heterocyclic compound, 59303-10-5, name is 2-Chloro-5-methylpyrazine, molecular formula is C5H5ClN2, 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.

NaH (60% in mineral oil, 103 mg, 2.57 mmol) was added to a stirred solution of l-Boc- 4-hydroxypiperidine (CAS: 109384-19-2; 470 mg, 2.33 mmol) in DMF (10 mL) at 0 C under N2 atmosphere. The mixture was stirred at room temperature for 1 h. 2-Chloro-5- methylpyrazine (CAS: 59303-10-5; 300 mg, 2.33 mmol) was added to the mixture under N2 atmosphere and the reaction mixture was stirred at 50 C for 16 h. A solution of 1- Boc-4-hydroxypiperidine (CAS: 109384-19-2) in DMF which was stirred for 1 h at room temperature was added, and the reaction mixture was stirred at 80 C for another 16 h. The mixture was diluted with water and extracted with DCM. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 80:20). The desired fractions were collected and concentrated in vacuo to afford intermediate 151 (320 mg, 47%) as a white solid.

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

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BARTOLOME-NEBREDA, Jose Manuel; TRABANCO-SUAREZ, Andres, Avelino; DE LUCAS OLIVARES, Ana Isabel; DELGADO-JIMENEZ, Francisca; CONDE-CEIDE, Susana; VEGA RAMIRO, Juan, Antonio; (245 pag.)WO2019/243530; (2019); 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. 13535-07-4, name is 2-Amino-5-ethylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Amino-5-ethylpyrazine

To a solution of (4S)-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine (600 mg, 2.378 mmol), triphosgene (706 mg, 2.378 mmol) and triethylamine (1.989 mL, 14.27 mmol) in tetrahydrofuran (THF) (15 mL) stirred under nitrogen at room temperature for 30 min was added 5-ethylpyrazin-2-amine (879 mg, 7.13 mmol). The reaction mixture was stirred at 70 C. for 16 h and cooled to room temperature and then the reaction mixture was poured in to water and extracted with EtOAc (3×15 mL). The combined organic layers were washed with water, brine solution, dried over sodium sulfate and evaporated to give crude compound (TLC eluent: 5% MeOH in DCM: Rf-0.1; UV active). The crude compound was purified by column chromatography using Neutral Alumina and eluted with 30% EtOAc/Pet ether to afford pure (4S)-N-(5-ethylpyrazin-2-yl)-7-(6-methylpyridin-3-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (383 mg, 0.953 mmol, 40.1% yield), LCMS (m/z): 402.3 [M+H]+. 1H NMR (400 MHz, CDCl3): delta ppm 13.65 (s, 1H) 9.41 (d, J=1.53 Hz, 1H) 9.11 (d, J=2.19 Hz, 1H) 8.41 (dd, J=8.22, 2.52 Hz, 1H) 8.22 (d, J=1.32 Hz, 1H) 7.61 (d, J=7.89 Hz, 1H) 7.40 (d, J=8.11 Hz, 1H) 7.32 (d, J=8.11 Hz, 1H) 5.70 (dd, J=6.03, 3.18 Hz, 1H) 3.34-3.13 (m, 3H) 3.02 (dd, J=12.06, 3.29 Hz, 1H) 2.83 (q, J=7.53 Hz, 2H) 2.64 (s, 3H) 2.40-2.34 (m, 1H) 2.15-2.03 (m, 1H) 1.33 (t, J=7.56 Hz, 3H).

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 13535-07-4.

Reference:
Patent; BLUM, Charles A.; Caldwell, Richard Dana; Casaubon, Rebecca; Disch, Jeremy S.; Fox, Ryan Michael; Koppetsch, Karsten; Miller, William Henry; NG, Pui Yee; Oalmann, Christopher; Perni, Robert B.; Szczepankiewicz, Bruce G.; White, Brian; US2015/152108; (2015); 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. 58139-04-1, name is 2-Iodo-3-methoxypyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2-Iodo-3-methoxypyrazine

Intermediate 25 (0.15 g, 0.622 mmol) was dissolved in 1,4-dioxane (6 mL). 2-Iodo-3-methoxypyrazine (0.12 g, 0.508 mmol), cesium carbonate (0.405 g, 1.244 mmol, 1,1′-bis(diphenylphosphino)ferrocene (0.052 g, 0.093 mmol) and tris(dibenzylideneacetone) dipalladium(0) (0.028 g, 0.031 mmol) were added. The reaction tube was sealed and the mixture was stirred at 160 C. for 1 hour under microwave irradiation. After cooling, the reaction mixture was diluted with DCM and filtered over dicalite. The filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel; eluent: 7 M solution of ammonia in methanol/DCM 0/100 to 5/95). The desired fractions were collected and concentrated. This crude was further purified by preparative HPLC on (Chiralpal Diacel AS 20*250 mm) Mobile phase (CO2, MeOH with 0.2% iPrNH2) to yield compound 8 (0.010 g, 5% yield).

According to the analysis of related databases, 58139-04-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Janssen Pharmaceutica NV; Gijsen, Henricus Jacobus Maria; Van Brandt, Sven Franciscus Anna; US2014/364428; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, 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. Recommanded Product: 2-Bromo-5H-pyrrolo[2,3-b]pyrazine

2-bromo-5H-pyrrolo[2,3-b]pyrazine (5 g, 25 mmol) was added to chlorosulfonic acid (20 mL) at 0C. The reaction was heated to 100-120C for 2.5 hours before cooling and pouring into ice-water (80 mL). The solution was extracted into EtOAc (2 x 100 mL), the organic layers combined, washed with brine, dried over sodium sulphate and concentrated in vacuo. The residue was added to a solution of isopropylamine (881 mg, 15 mmol) and triethylamine (2.66 g, 26 mmol) in DCM (60 mL) at 0C. The reaction was stirred at 0C for 3 hours, diluted with water (50 mL) and extracted into EtOAc (2 x 80 mL). The organic layers were combined, washed with brine, dried over sodium sulphate and concen- trated in vacuo. The solid was triturated with TBME to afford the title compound (2 g, 49% over 2 steps) as a brown solid that was used directly in the next step.

The synthetic route of 875781-43-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; THORARENSEN, Atli; BROWN, Matthew Frank; CASIMIRO-GARCIA, Agustin; CHE, Ye; FLANAGAN, Mark Edward; GILBERT, Adam Matthew; HAYWARD, Matthew Merrill; TELLIEZ, Jean-Baptiste; UNWALLA, Rayomand Jal; TRUJILLO, John I.; LIANG, Sidney Xi; (212 pag.)WO2016/178110; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 122-05-4, name is Pyrazine-2,5-dicarboxylic 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 122-05-4, Product Details of 122-05-4

A ScCl3·6H2O (30 mg, 0.116 mmol) solution in distilled water (1.0 ml)was mixed with a H2pzc dihydrate solution (35 mg, 0.171 mmol) in N,N-dimethylformamide (1.0 ml). Acetonitrile (2.0 ml)and 0.25 ml of concentrated hydrochloric acid were added to the mixture. The prepared reaction mixture was placed intoa sealed glass tube and kept at 100 C for 24 h. The obtained colorless plate-like crystals were filtered off, washed by twoportions (2 ml) of acetonitrile and dried in air. The product yield was 40 mg (89%). Elemental analysis: found (%) C 37.1,H 3.4, N 14.2. Calculated for C24H24N8O16Sc2 (%): C 37.4, H 3.1, N 14.5. IR spectrum (KBr), v, cm-1: 392 (m), 427 (m),490 (m), 510 (s), 530 (s), 694 (m), 776 (s), 846 (s), 950 (w), 1051 (s), 1121 (m), 1179 (s), 1298 (s), 1386 (s), 1477 (s),1673 (s), 2510 (w), 2818 (w), 3104 (w), 3380 (w), 3491 (w).

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:
Article; Barsukova; Sapianik; Samsonenko; Fedin; Journal of Structural Chemistry; vol. 60; 5; (2019); p. 823 – 829; Zh. Strukt. Kim.; vol. 60; 5; (2019); p. 857 – 863,7;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 1458-01-1 as follows. Application In Synthesis of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate

3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. Yield: 99.6 g (107percent of theory) C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-

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:
Patent; Boehringer Ingelheim International GmbH; HECKEL, Armin; Frattini, Sara; Hamprecht, Dieter; Kley, Joerg; US2013/109697; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem