Month: August 2021

Adding a certain compound to certain chemical reactions, such as: 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, 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 939412-86-9, Application In Synthesis of (3-Chloropyrazin-2-yl)methanamine hydrochloride

A mixture of (3-chloropyrazin-2-yl)methanamine hydrochloride (5 g, 21.38 mmol), (trans)-4- ((benzyloxycarbonylamino)methyl)cyclohexanecarboxylic acid (6.23 g, 21.38 mmol), 1 -ethyl-3-(3- dimethylaminopropyl) carbodiimide) hydrochloride (4.51 g, 23.52 mmol), 1 -hydroxy-7-azabenzotriazole (1.455 g, 10.69 mmol), and triethyl amine (4.76 ml, 34.2 mmol) in dichloromethane (60 ml) was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by column chromatography (silica gel, dichloromethane with gradient 0.5 to 5% of methanol) to yield benzyl ((trans)-4- ((3-chloropyrazin-2-yl)methylcarbamoyl)cyclohexyl)methylcarbamate (8.79 g).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (3-Chloropyrazin-2-yl)methanamine hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; N.V. ORGANON; MAN de,, Adrianus Petrus Antonius; REWINKEL,, Johannes Bernardus Maria; JANS,, Christiaan Gerardus Johannes Maria; RAAIJMAKERS,, Hans Cornelis Andreas; WIJKMANS,, Jacobus Cornelis Henricus Maria; WO2011/95556; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 98-97-5, 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. 98-97-5, name is Pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Example 1 A. 4-Azido-1-thiophen-2-yl-butan-1-one A mixture of 4-chloro-2′-butyrothienone (3.0 g, 15.9 mmol) and sodium azide (2.07 g, 31.8 mmol) in DMF (50 mL) was stirred at 70 C. for 1.5 h. The reaction mixture was then partitioned between ethyl acetate (200 mL) and water (200 mL). The organic layer was washed with water (100 mL), saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL) and dried over sodium sulfate. Removal of the solvent in vacuo provided the title compound (2.58 g, 83% yield). MS m/e 218; HPLC retention time 0.85 min (Method B). B. 2-(2-Azido-ethyl)-1-pyrazin-2-yl-3-thiophen-2-yl-propane-1,3-dione A suspension of pyrazine 2-carboxylic acid (2.52 g, 20.3 mmol) in dichloromethane (30 mL) at 0 C. was treated with oxalyl chloride (1.95 mL, 22.3 mmol) followed by the addition of catalytic DMF (1 drop). The reaction mixture was allowed to warm to room temperature overnight, then concentrated in vacuo to give pyrazine 2-carbonyl chloride as a violet-colored solid. In a separate reaction flask, LHMDS (1.0 M in THF, 11.28 mL) was added dropwise to a solution of the ketone 1A (1.10 g, 5.64 mmol) in THF (10 mL) at -78 C. The reaction mixture was maintained at that temperature for 20 min. The pyrazine 2-carbonyl chloride (1.0 g, 5.64 mmol)was then rapidly introduced as a solid to the reaction mixture to give a dark brown solution which was maintained at -78 C. for another 20 min. The reaction mixture was then partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, then concentrated to give the crude oil. Purification by flash column chromatography (silica, 30% ethyl acetate in hexanes) provided the title compound as a yellow oil (939 mg, 55% yield). MS m/e 324; HPLC retention time 2.78 min (Method A). 1H NMR (400 MHz, CDCl3): delta 2.36 (m, 1 H), 2.58 (m, 1 H), 3.60 (dd, 2 H), 5.82 (dd, 1 H), 7.28 (dd, 1 H), 7.82 (d, 1 H), 8.07 (d, 1 H), 8.67 (s, 1 H), 8.88 (s, 1 H), 9.37 (s, 1 H). C. 2-[4-(2-Azido-ethyl)-5-thiophen-2-yl-2H-pyrazol-3-yl]-pyrazine A solution of the dione 1B (213 mg, 0.71 mmol), hydrazine monohydrate (0.17 mL, 3.54 mmol) and concentrated aqueous HCl (1 drop) in methanol (4 mL) was heated at 70 C. for 1 h. The reaction mixture was then concentrated to give a yellow sticky solid which was purified by flash column chromatography (silica, 1:1 ethyl acetate:hexanes) to give the title compound (142 mg, 67% yield) as a colorless oil. MS m/e 298; HPLC retention time 3.40 min (Method A). 1H NMR (400 MHz, CDCl3): delta 3.29 (t, 2 H), 3.58 (t, 2 H), 7.13 (dd, 1 H), 7.41 (m, 2 H), 8.45 (d, 1 H), 8.59 (b s, 1 H), 9.25 (s, 1 H). D. 2-(5-Pyrazin-2-yl-3-thiophen-2-yl-1H-pyrazol-4-yl)-ethylamine A mixture of the azide 1C (140 mg, 0.47 mmol), and palladium on carbon (10% w/w, 30 mg) in methanol (5 mL) was stirred under an atmosphere of hydrogen gas (1 atm, balloon) for 3 h. The reaction mixture was then flushed with nitrogen and the mixture filtered over celite. Concentration under reduced pressure gave the title compound (104 mg, 82% yield) as a yellow oil. MS m/e 272; HPLC retention time 1.57 min (Method A). E. 2-Chloroethanol (0.095 mL, 1.41 mmol) was added dropwise to a solution of chlorosulfonyl isocyanate (0.122 mL, 1.41 mmol) in dichloromethane at -20 C. The reaction mixture was warmed to 0 C. and maintained at that temperature 1.5 h. The solution was then transferred by canula to a solution of the amine XX (383 mg, 1.41 mmol) and triethylamine (1.38 ml, 9.9 mmol) in dichloromethane at -10 C. The reaction mixture was then stirred 17 h at room temperature under nitrogen to give a clear olive-green solution. A portion of the solution of intermediate sulfamolyoxazolidinone was concentrated to give a greenish solid (30 mg) which was taken up in acetonitrile (3 mL) and treated with triethylamine (0.059 mL, 0.42 mmol) and R-(1-benzyl-pyrrolidin-3-yl)-methyl-amine (0.013 mL, 0.046 mmol). The reaction mixture was heated at 70 C. 16 h, then concentrated and purified by reverse phase preparative HPLC to provide 25 mg of the title compound. MS m/e 525; HPLC retention time 2.31 min (Method A). 1H NMR (CD3OD): delta 1.95 (b s, 2H), 2.52 (b s, 2 H), 3.00 (s, 3 H), 3.10-3.40 (b m, 5 H), 4.15 (b s, 2 H), 4.20-4.40 (b m, 2 H), 6.96 (dd, 1 H), 7.20 (d, 1 H), 7.25 (m, 5 H), 7.33 (d, 1 H), 8.31 (s, 1 H), 8.44 (s, 1 H), 8.93 (s, 1 H). 1H NMR (CDCl3): delta 0.83 (t, 3H), 1.3 (dd, 2H), 1.39 (s, 9H), 1.40 (t, 2H), 1.45 (bm, 2H), 1.75 (bs, 2H), 2.1 (bs, 2H), 2.4 (bs, 2H), 2.76 (s, 3H)

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

Reference:
Patent; Ngu, Khehyong; Weinstein, David S.; Robl, Jeffrey A.; US2005/70589; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 16298-03-6, These common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, 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.

Methyl 3-aminopyrazine-2-carboxylate (100 g, 653.0 mmol) and N- bromosuccinimide (1 16.2 g, 653.0 mmol) were stirred in MeCN (1.198 L) at ambient temperature for 15 hours. The resultant precipitate was isolated by filtration and washed with MeCN (10 mL) and diethyl ether (100 mL) to give the sub-title product as pale yellow flakes (123.73g, 82percent Yield). 1H NMR (400.0 MHz, CDCl3) delta 4.00 (s, 3H), 6.47 (br s, 2H), 7.28 (s, 1H) and 8.31 (s, 1H) ppm; (ES+) 232.0.

Statistics shows that Methyl 2-aminopyrazine-3-carboxylate is playing an increasingly important role. we look forward to future research findings about 16298-03-6.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; YOUNG, Stephen, Clinton; STORCK, Pierre-Henri; VIRANI, Aniza, Nizarali; REAPER, Philip, Michael; PINDER, Joanne; WO2011/143423; (2011); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 14508-49-7, A common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, molecular formula is C4H3ClN2, 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.

General procedure: A 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n.

The synthetic route of 14508-49-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xu, Chen; Li, Hong-Mei; Wang, Zhi-Qiang; Fu, Wei-Jun; Inorganica Chimica Acta; PA; (2014); p. 11 – 15;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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

A.1. Synthesis of lM-1A.1.1. Experimental procedure for the synthesis of IM-1SM-1 SM-5a IM-1a2-Bromo-5/-/-pyrrolo[2,3- 5]pyrazine SM-1 (500 mg, 2.5 mmol), 1-Boc-4-(methylamino)- piperidine SM-5a (1.082 g, 5.0 mmol), Pd2(dba)3 (139 mg, 0.1 mmol), DavePhos (238 mg, 0.6 mmol) and LiHMDS (12.625 mL, 12 mmol) are taken-up in dry THF (10 mL) and the resulting mixture is flushed with Argon and stirred for 1 h at 80 C. The reaction mixture is diluted with H20 and AcCN, Isolute is added, the solvent is removed in vacuo and the residue is purified via RP HPLC. The product containing fractions of IM-1 a (HPLC-MS method A: tRet. = 1.72 min; MS (M+H)+ = 332) are freeze dried.

The synthetic route of 2-Bromo-5H-pyrrolo[2,3-b]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; STADTMUELLER, Heinz; WO2012/104388; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 1458-18-0, The chemical industry reduces the impact on the environment during synthesis 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

General procedure: To a solution of methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate (1.0 eq.) in 2-propanol (5 mL/mmol), an appropriate primary or secondary amine(3-6 eq.) was added, and the reaction mixture wasrefluxed for 2 h.10) The solution was cooled to roomtemperature, concentrated under reduced pressure, andthe residue was purified by silica-gel column chromatography(Wako gel C-200, 30-40% ethyl acetate/n-hexane) to afford the series 1 intermediate (yield:32-95%). The regioselectivity of the nucleophilicsubstitution at the 5-position of the pyrazine ring wasconfirmed by an X-ray structural analysis (Fig. S1).

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, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Murai, Masatoshi; Habu, Sayako; Murakami, Sonomi; Ito, Takeshi; Miyoshi, Hideto; Bioscience, Biotechnology and Biochemistry; vol. 79; 7; (2015); p. 1061 – 1066;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486460-21-3,Some common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C6H7F3N4, 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 solution of (R) -3- [N- (tert- butoxycarbony1) amino] -4- (2, 4, 5-trifluoro-phenyl) butanoic acid ( 0.333 g, lmmol) of Example 8 and 3- ( trif luoromethyl- 5, 6, 7, 8-tetrahydro-l, 2, 4-triazolo [4, 3a] pyrozine (0.192 g, 1 mmol) in DMF (12 ml) was added HOBT (0.162 g, 1.2mmol) and EDC (0.230 g. 1.2 mmol) at 0 0C. After being stirred at room temperature for 16 h, DMF was evaporated and the residue extracted with ethyl acetate (3 X 20 ml) . The organic extracts were washed with NaHSO4 aq, then NaHCO3, then brine, and then dried over Na2SO4. Concentration was followed by purification by flash chromatography to afford 0.375 g of the title compound (71.8%) . 1H NMR (300 MHz, CDCl3) 7.10-7.00 (m, IH), 7.00-6.90 (m, IH), 5.25-5.35 (br, IH), 5.10-5.00 (m, IH), 4.90 (s, IH), 4.30-3.90 (m, 5H), 3.00-2.90 (m, 2H), 2.80-2.60 (m, 2H), 1.35 (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 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, its application will become more common.

Reference:
Patent; CHIRAL QUEST, INC.; WU, Shulin; YU, Bo; WANG, Yejing; DELICE, Alain; ZHU, Jingyang; WO2010/78440; (2010); 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. 54608-52-5, name is 2-Hydrazinopyrazine, A new synthetic method of this compound is introduced below., SDS of cas: 54608-52-5

To a mixture of 2.38 g (21.6 mmol) of 2-hydrazinopyrazine and 2.41 g (3.32 mL, 23.8 mmol) of triethylamine in 50 mL of acetonitrile was added 3.25 g (2.66 mL, 23.8 mmol) of ethyl chloro (oxo) acetate at 0 C. The reaction mixture was stirred at ambient temperature for 18 h, and then partitioned between aqueous sodium bicarbonate solution and ethyl acetate. The aqueous phase was extracted with three portions of ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate, and concentrated to give the title compound. LC/MS 211 (M+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; MERCK & CO., INC.; WO2004/58266; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 123-32-0, A common heterocyclic compound, 123-32-0, name is 2,5-Dimethylpyrazine, molecular formula is C6H8N2, 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.

2,5-dimethylpyrazine (0.5 g, 0.00462 mol) and 1-methylpyr-role-2-carboxaldehyde (1.513 g, 0.0138 mol) were dissolved in DMFand the mixture was cooled to 0 C (Scheme 1). To this mixture,potassium-tert-butanolate (1.55 g, 0.013 mol) were added in smallportions and the mixture was brought to ambient temperature andstirring was continued until all starting material had beenconsumed (TLC). After the completion of the reaction, waterwas added, and the product was isolated by extraction withchloroform. The organic layer was concentrated in vacuum and thesolid material obtained was recrystallized to give the product(1.2 g, 42%) as an orange solid. The structure of the compound wasconfirmed by IR and 1H and 13C NMR techniques.1H NMR (CDCl3, 500 MHz): delta = 3.7 (s, 6H), 6.16 (m, 2H), 6.64 (m,2H), 6.72 (m, 2H), 6.86 (d, 2H, J = 15.4 Hz), 7.60 (d, 2H, J = 15.4 Hz),8.42 (s,2H). 13C NMR (CDCl3, 150 MHz): delta = 34.2, 107.9, 108.2, 119.3,120.6, 122.1, 128.5, 140.1, 147.8.

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; El-Daly, Samy A.; Asiri, Abdullah M.; Alamry, Khalid A.; Osman, Osman I.; Journal of Photochemistry and Photobiology A: Chemistry; vol. 312; (2015); p. 64 – 72;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 109838-85-9, These common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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.

A 5 L- 3 necked round bottomed flask, equipped with a mechanical stirrer, temperature probe, addition funnel and N2 inlet, was charged with the Schollkopf chiral auxiliary-(Int-13a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-13b, 256 g, 1.63 mol, 1.5 eq), and THF (2 L, Aldrich anhydrous). The flask was cooled in a dry ice/ 2- propanol bath until the internal temperature reached -75 °C. n-Butyllithium (Aldrich 2.5 M in hexanes , 478 mL, 1.19 mol, 1.09 eq) was added via a dropping funnel over 1 hour while maintaining the internal reaction temperature between -67 °C and -76 °C. The resulting orange-red solution was allowed to gradually warm to room temperature for about 15 hours. The reaction mixture was then re-cooled to 0 °C and quenched with 500 mL of water.Diethyl ether (2L) was added and the layers were separated. The aqueous layer was extracted with 1 L of diethyl ether. The combined organic extracts was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to dryness, giving 480 g of orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil. The crude product was split into two batches and purified via silica gel chromatography on a 1.6 kg flash column. The column was eluted with gradient of 0-4percent Et20 in hexanes. The product fractions were concentrated in vacuo at a bath temperature at or below 40 °C giving 190 grams of Int-13c-(60percentyield).

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

Reference:
Patent; SCHERING CORPORATION; COBURN, Craig, A.; LAVEY, Brian, J.; DWYER, Michael, P.; KOZLOWSKI, Joseph, A.; ROSENBLUM, Stuart, B.; WO2012/50848; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem