Tag: M.W=100-200

Synthetic Route of 55557-52-3,Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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 3-chloropyrazine-2-carbonitrile 14 (4.60 g,32.96 mmol) in EtOH (120 mL) was added NaSH (3.94 g,42.79mmol), and themixture was stirred at roomtemperature for 3 h (TLC monitoring). EtOH was evaporated under reduced pressure,and the residue was dissolved in H2O and 2 M HCl was carefully added to neutralize the suspension. After evaporation of the solvent, the residue was dissolved in acetone (48 mL) and ClCH2CN (2.29 mL, 32.96 mmol), K2CO3 (4.55 g, 32.96 mmol), and a catalytic amount of KI were added. The resulting mixture was stirred at room temperature for 3 h, and then the resulting residue was separated by filtration and washed with acetone (3 30 mL). The filtrate was evaporated under reduced pressure, the resulting residue was dissolved in THF (240 mL), piperidine (3.26 mL, 32.96 mmol) was added, and the mixture was stirred at reflux for 5 h. After cooling, the solution was concentrated to dryness, and the residual material was purified by column chromatography (eluent: 100% dichloromethane) to give 7-aminothieno[2,3-b]pyrazine-6-carbonitrile 1d as a yellow powder (3.66 g, 63%); Rf ? 0.18 (dichloromethane); mp 205e207 C (lit. [8b]: 205e 206 C); IR (KBr) nmax (cm 1): 3383, 3329, 3231 and 3204 (nNH2), 2197 (nCN), 1643, 1566 and 1529 (nC]C); 1H NMR (400 MHz, DMSO-d6): d 8.86 (d, 1H, J ? 2.4 Hz), 8.84 (d, 1H, J ? 2.4 Hz), 7.45 (br s, 2H, NH2); 13C NMR (100 MHz, DMSO-d6):d 154.55 (C), 149.15 (C), 145.26 (CH), 142.36 (CH), 139.76 (C), 115.37 (CN), 74.27 (C); MS (ESI) m/z (%): 177.0 (100) [M th H]th. Anal. Calcd for C7H4N4S: C, 47.72; H, 2.29; N, 31.80; S, 18.20. Found: C, 47.84; H,2.30; N, 31.86.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloropyrazine-2-carbonitrile, its application will become more common.

Reference:
Article; Loidreau, Yvonnick; Marchand, Pascal; Dubouilh-Benard, Carole; Nourrisson, Marie-Renee; Duflos, Muriel; Lozach, Olivier; Loaec, Nadege; Meijer, Laurent; Besson, Thierry; European Journal of Medicinal Chemistry; vol. 58; (2012); p. 171 – 183;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 38557-72-1, A common heterocyclic compound, 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, molecular formula is C6H7ClN2, 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.

[0450] Preparation Example 104: Preparation of (3,5-dimethylpyrazin-2-yl)piperazine hydrochloride[0451][0452] Under a nitrogen stream, to a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium(II) acetate (225 mg), 2-(dicyclohexylphosphino)-2?,4?,6?-triisopropyl-1,1?-biphenyl (953 mg) and sodium tert-butoxide(2.7 g) was added toluene (40 mL), and the mixture was stirred with heating under reflux for 8 hr. After cooling,the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent wasevaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g). The obtained (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL)was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added ethyl acetate(100 mL), and the precipitate was collected by filtration to give the title compound (3.3 g).

The synthetic route of 38557-72-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; MAEDA, Kazuhiro; ENDOH, Jun-ichi; TARAO, Akiko; TASHIRO, Kaoru; ISHIBUCHI, Seigo; HIKAWA, Hidemasa; EP2565182; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 312736-49-5, 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. 312736-49-5 name is 3,5-Dichloropyrazine-2-carboxylic acid, 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.

To a solution of 3,5-dichloropyrazine-2-carboxylic acid (0.304 g, 1.58 mmol) in MeOH (5 mL) and diethyl ether (5 mL) at room temperature was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 4.00 mL, 8.00 mmol). The reaction mixture was stirred at RT for 30 min and concentrated. Purification by flash column chromatography on silica gel (5% to 20% EtOAc in hexanes) gave methyl 3,5- dichloropyrazine-2-carboxylate (0.312 g, 1.51 mmol, 96%o yield) as a white solid. LC/MS (ESf) m/z = 207.0 (M+H) +

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dichloropyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; AMGEN INC.; MINATTI, Ana Elena; LOW, Jonathan, D.; ALLEN, Jennifer, R.; AMEGADZIE, Albert; BROWN, James; FROHN, Michael, J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul, E.; LOPEZ, Patricia; MA, Vu Van; NISHIMURA, Nobuko; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert, M.; SHAM, Kelvin; SMITH, Adrian, L.; WHITE, Ryan; XUE, Qiufen; WO2014/138484; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 912773-21-8,Some common heterocyclic compound, 912773-21-8, name is 2-Bromo-5-chloropyrazine, molecular formula is C4H2BrClN2, 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 tert-butyl (3aR, 5s,6a5)-5-aminohexahydrocyclopenta[c]pyrrole-2( 1 H)-carboxylate (274 mg, 1.21 mmol) in NIVIP (4.5 mL) was added 2-bromo-5-chloropyrazine (585 mg, 3.02 mmol) and J7N- diisopropylethylamine (0.63 mL, 3.63 mmol). The mixture was stirred at 180 C under microwave irradiation for 1 h. Solids were removed by syringe filtration, and crude residue was purified by RP-HPLC (20-70% MeCN in 0.05% NH4OH aqueous solution over 20 mm). Fractions containing product were combined and concentrated to give the title compound as a brown oil (148 mg, 32%). ES-MS [M+H]b = 383.2.

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

Reference:
Patent; VANDERBILT UNIVERSITY; LINDSLEY, Craig, W.; CONN, P., Jeffrey; ENGERS, Darren, W.; ENGERS, Julie, L.; TEMPLE, Kayla, J.; BENDER, Aaron, M.; BAKER, Logan A.; (221 pag.)WO2019/79783; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 13134-31-1, These common heterocyclic compound, 13134-31-1, name is 2,3-Diaminopyrazine, 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 mixture of 2,3-diaminopyrazine (55mg, 0.5mmol) and methyl 1-({5-chloro-2-[(2- methylpropyl)oxy]phenyl}methyl)-5-methyl-1/-/-pyrazole-3-carboximidoate hydrochloride (186mg, O.deltammol) in ethanol (4ml) was stirred and refluxed for 4 hours. The solid which separated was filtered, dissolved in hot methanol and 1 M hydrogen chloride in ether (0.5ml) added. The solution was evaporated to dryness and the residue triturated with ether to give the title compound as an off-white solid (17mg). LC/MS Rt 3.10, [MH]+ 397.2, 399.2

The synthetic route of 13134-31-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; WO2006/114313; (2006); 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. 6863-73-6, name is 3-Chloropyrazin-2-amine, A new synthetic method of this compound is introduced below., Recommanded Product: 6863-73-6

N. 1 -IMIDAZO[ 1 ,2-A]PYRAZIN-8-YL-3 -TRIFLUOROMETHYL- IH-P YRAZOLE-4-C ARBOXYLIC ACID (I -P YRIDIN-3 -YL-CYCLOHEXYLMETHYL)-AMIDE (COMPOUND 14); Step 1. 8-Chloro-imidazol[l,2-a]pyrazine; HBr (48% in H2O) is added to a solution of 2-amino-3-chloropyrazine (1.2 g, 9.26 mmol) and BrCH2CH(OEt)2 (1.6 mL, 10 mmol) in MeOH and H2O (5 mL and 10 mL) at RT. The mixture is stirred for 24 h at RT and then heated to 40 C for 48 h. The pH is adjusted to 7 with sat. Na2Ctheta3. The mixture is extracted with CH2Cl2. The organic phase is dried over anhydrous Na2SO^ The product is purified by silica gel column chromatography (4%MeOH in CH2Cl2) to give the title compound as an off white solid.

The synthetic route of 6863-73-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NEUROGEN CORPORATION; WO2009/12482; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 875781-43-4, A common heterocyclic compound, 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, molecular formula is C6H4BrN3, 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.

To a solution of commercially available 2-bromo-5H-pyrrolo[2,3-b]pyrazine (1.00 g, 5.05 mmol) in N,N-dimethylformamide (10 mL) was added Cs2C03 (2.50 g, 7.67 mmol) and [2-(chloromethoxy)ethyl]trimethylsilane (1.26 g, 7.55 mmol). The reaction mixture was stirred overnight at room temperature and concentrated under vacuum. The residue was purified by flash chromatography on silica gel (solvent: 1/10 ethyl acetate/petroleum ether). Appropriate fractions were combined and evaporated to afford 2-bromo-5-[[2-(trimethylsilyl)ethoxy]methyl]-5H-pyrrolo[2,3-b]pyrazine (1.50 g, 90%) as a yellow solid. LC/MS (Method D, ESI): [M+H]+ = 328.0, RT = 1.23 min.

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; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; ZAK, Mark; ROMERO, F. Anthony; YUEN, Po-wai; HANAN, Emily J.; (139 pag.)WO2018/166993; (2018); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

21279-62-9, name is 3-Chloropyrazine-2-carboxamide, 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. HPLC of Formula: C5H4ClN3O

General procedure: Compounds 1-6 were prepared according to conventional organic synthesis methods. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was dissolved in THF (20 mL) in a round bottom flask and after that treated with two equivalents of the corresponding benzylamine and an equimolar amount of triethylamine. The reaction was conducted with continuous stirring and heating (70 C) under reflux in an oil bath for 15 h. Compounds 7-15 were synthesised using a microwave reactor with a focused field. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was put into a thick-walled tube together with the corresponding benzylamine (2.54 mmol), pyridine (1.27 mmol), methanol (approx. 5 mL) and a magnetic stir bar and then sealed with a special cap. The reaction parameters were set according to the previously published paper as follows-140 C, 30 min, 200 W [29]. Reaction progress was checked by TLC (hexane:ethyl acetate-1:1). Regardless of the synthesis method used,all reaction mixtures were adsorbed on silica and subjected to preparative flash chromatography (hexane and ethyl acetate, gradient elution, detection wavelengths 260 nm and 280 nm). Products were recrystallized from ethanol or ethanol and water if necessary. All final substances were chemically characterized (1H-NMR, 13C-NMR, IR, melting point and elemental analysis).

The synthetic route of 21279-62-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jandourek, Ondrej; Tauchman, Marek; Paterova, Pavla; Konecna, Klara; Navratilova, Lucie; Kubicek, Vladimir; Holas, Ondrej; Zitko, Jan; Dolezal, Martin; Molecules; vol. 22; 2; (2017);,
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 55557-52-3 as follows. Computed Properties of C5H2ClN3

General procedure: Compounds 5-10 (Supplemental Figure 6A, Scheme 1), 12-15 (Supplemental Figure 6B, Scheme 2), and 17, 18 (Supplemental Figure 6C, Scheme 3) were prepared by a modified procedure as reported by Kayser F. et al. (ref 1) and Chen Z. et al. (ref. 2). To a solution of the corresponding thiol, or phenol 4 (0.85 g, 5.0 mmol) in 15 ml DMF (N, N-Dimethylformamide) 3-chloropyrazine-2-carbonitrile (0.66 g, 4.76 mmol) and Na2CO3 (1.01 g, 9.52 mmol), or substituted chrolopyridines, or chlorobenzenes, were added respectively and the resulting mixture was refluxed at 80 C for 12 h. The DMF was evaporated at reduced pressure and the compound A residue was recrystallized from ethyl acetate. The rest of the compounds were purified by flash chromatography on silica gel with ethyl acetate:hexanes (5-100% gradient).

According to the analysis of related databases, 55557-52-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Freeman, Lita A.; Demosky, Stephen J.; Konaklieva, Monika; Kuskovsky, Rostislav; Aponte, Angel; Ossoli, Alice F.; Gordon, Scott M.; Koby, Ross F.; Manthei, Kelly A.; Shen, Min; Vaisman, Boris L.; Shamburek, Robert D.; Jadhav, Ajit; Calabresi, Laura; Gucek, Marjan; Tesmer, John J. G.; Levine, Rodney L.; Remaley, Alan T.; Journal of Pharmacology and Experimental Therapeutics; vol. 362; 2; (2017); p. 306 – 318;,
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. 123-32-0, name is 2,5-Dimethylpyrazine, A new synthetic method of this compound is introduced below., Safety of 2,5-Dimethylpyrazine

General procedure: A mixture of AgNO3 (0.051 g, 0.3 mmoL), H2ntph (0.063 g, 0.3mmol) and pyz (0.024 g, 0.3 mmoL) were dissolved in H2O/acetonitrile(10 mL, 1:1), after stirred for 20 min in air and then the mixturewas transferred to a 25 mL stainless steel reactor and heatedto 110 C for 72 h. And then the reaction system was cooled toroom temperature, colorless needle crystals of 1 were obtained.Yield based on Ag: 72%.

The synthetic route of 123-32-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yang, Yuan-Yuan; Zhou, Lin-Xia; Zhu, Hong-Lin; Li, Wen-Ying; Zheng, Yue-Qing; Polyhedron; vol. 148; (2018); p. 161 – 170;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem