Pyrazines

Reference of 87486-34-8,Some common heterocyclic compound, 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, molecular formula is C5H4Br2N2O, 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 109c 5-Bromo-3-(l-cyclopropyl-lH-pyrazol-4-ylamino)-l-methylpyrazin- -one 109cCGIPHARM60WOA 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 109b (378 mg, 3.07 mmol), 3,5- dibromo-l-methylpyrazin-2(lH)-one (906 mg, 3.38 mmol), cesium carbonate (3.00 g, 9.21 mmol), and 1,4-dioxane (45 mL). After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (151 mg, 0.261 mmol) and tris(dibenzylidene-acetone)dipalladium(0) (141 mg, 0.154 mmol) were added, and the reaction mixture was heated at reflux for 3 h. After this time, the mixture was cooled to room tempera-ture and diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 x 45 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0percent to 10percent methanol/methylene chloride) to afford a 28percent yield (266 mg) of 109c as an off-white solid: mp 228-230 °C; ]H NMR (300 MHz, DMSO-i3/4) delta 9.90 (s, 1H), 8.06 (s, 1H), 7.69 (s, 1H), 7.21 (s, 1H), 3.70 (m, 1H), 3.41 (s, 3H), 0.96 (m, 4H); MS (ESI+) m/z 310.0 (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 3,5-Dibromo-1-methylpyrazin-2(1H)-one, its application will become more common.

Reference:
Patent; GILEAD CONNECTICUT, INC.; GENENTECH, INC.; CURRIE, Kevin S.; WANG, Xiaojing; YOUNG, Wendy B.; WO2012/31004; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 122-05-4, name is Pyrazine-2,5-dicarboxylic acid, 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. Quality Control of Pyrazine-2,5-dicarboxylic acid

Dimethyl Pyrazine-2,5-dicarboxylate (83). Hydrogen chloride gas was bubbled (approx. 5 min) into a stirred suspension of 82 (0.5 g, 2.97 mmol) in methanol (25 ml) and the mixture refluxed for 4 hours. Solvent was evaporated under reduced pressure and the residual solid dissolved in chloroform. The chloroform solution was washed with 10% sodium carbonate solution and water, dried (MgSO4) and evaporated under reduced pressure. Solid obtained was recrystallized from methanol to afford 0.42 g (72.2%) of colorless needles mp 167-169 C. [lit. Spoerri, P. E. and Erickson, A. J. Amer. Chem. Soc. 1938, 60, 400-402, mp 168-169 C. (sealed capillary)]; IR (KBr) cm-1 1720 (ester); NMR (CDCl3, 90 MHz) delta 4.09 (s, 6H, CO2 CH3), 9.40 (s, 2H, aromatic). Anal. calcd. for C8 H8 N2 O4: C, 48.98; H, 4.11; N, 14.28. Found: C, 48.89; H, 4.33; N, 14.12.

The synthetic route of Pyrazine-2,5-dicarboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Ohio State University; US4871736; (1989); 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. 117719-17-2, name is 5-Bromo-3-morpholinopyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 117719-17-2

A mixture of intermediate 1-02 (360 mg, 1.35 mmol), indazole-4-boronic acid hydrochloride (600 mg, 2.97mmol), K2C03 (2 mE of saturated solution), PdC12(dppf). DCM (112 mg, 0.135 mmol) in DME (5 mE) was heatedunder microwave irradiation for 10 mm at 130 C. Thereaction mixture was filtered through a celite pad, washingwith DCM. The filtrate was dried over Na2SO4 and concentrated. The crude was purified by flash column chromatography (Isolute Si 1110 g cartridge) eluting with a gradient ofDCMJMeOH (from 100% to 90:10) to yield 250 mg of theintermediate 1-03 pure (Y: 62%).

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 117719-17-2.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO); Serrano Marugan, Manuel; Pastor Fernandez, Joaquin; Martinez Gonzalez, Sonia; Ortega Molina, Ana; Bischoff, James R.; Oyarzabal Santamarina, Julen; (220 pag.)US9993554; (2018); B2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 369638-68-6, 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. 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, This compound has unique chemical properties. The synthetic route is as follows.

tert-butyl 5-methylpyrazin-2-yl carbamate (6.27 g, 30.0 mmol) was weighed and dissolved in 30 mL dichloromethane, and in an ice water bath, 20 mL trifluoroacetic acid was added slowly. It was moved to react at room temperature for 1 hour, rotate evaporated to dryness to remove the solvent, and was used for the next step directly.

The chemical industry reduces the impact on the environment during synthesis tert-Butyl (5-methylpyrazin-2-yl)carbamate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; KBP Biosciences Co., Ltd.; ZHANG, Yan; ZHANG, Min; LO, HoYin; (52 pag.)EP2781508; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 41110-28-5, These common heterocyclic compound, 41110-28-5, name is 3-Methylpyrazine-2-carboxylic acid, 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 1.1: Preparation of 3-methyl-pyrazine-2-carboxylic acid ethyl esterTo a solution of 3-methyl-pyrazine-2-carboxylic acid (10 g) (commercially available) and jV,7V-dimethylformamide (“DMF”) (1 drop) in dichloromethane (20 ml) at ambient temperature was added drop wise oxalyl chloride (2.57 ml). The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was concentrated and the residue dissolved in dichloromethane (20 ml). Triethylamine (4.04 ml) was added to this solution followed by drop wise addition of ethanol (10 ml). The reaction mixture was stirred at ambient temperature for one hour and then concentrated. The residue was purified by chromatography on silica gel (eluent: 0-10% v/v ethyl acetate in zso-hexane) to give 3- methyl-pyrazine-2-carboxylic acid ethyl ester (9.85 g). MH+ = 167, RT = 0.73 min (Method A). IH-NMR (400 MHz, CDCl3): 8.61 (d, IH), 8.54 (d, IH), 4.49 (q, 2H), 2.85 (s, 3H), 1.46 (t, 3H) ppm.

Statistics shows that 3-Methylpyrazine-2-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 41110-28-5.

Reference:
Patent; SYNGENTA LIMITED; WILLETTS, Nigel, James; MULHOLLAND, Nicholas, Phillip; WORTHINGTON, Paul, Anthony; AVERY, Alaric, James; WO2010/130970; (2010); A1;,
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 313339-92-3 as follows. HPLC of Formula: C5HCl2N3

(ii) 2,3-Dichloro-N-[4-(6-chloro-5-cyano-pyrazin-2-yl)phenyl]benzenesulfonamide 2,3-Dichloro-N-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-benzenesulfonamide (5.78 g) was added to a reaction vessel containing a magnetic stirring bar together with 3,5-dichloro-pyrazine-2-carbonitrile (2.35 g), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (Pd(dppf)2Cl2) (791 mg) and cesium carbonate (13.2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100 C. under stirring. After 3 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (100 ml) and extracted with EtOAc (3*200 ml). The combined aqueous phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded 2,3-dichloro-N-[4-(6-chloro-5-cyano-pyrazin-2-yl)-phenyl]-benzenesulfonamide as a light brown foam after evaporation of the solvents under reduced pressure. Yield: 4.32 g (73%). MS (ES-): m/e=436.0 (M-H).

According to the analysis of related databases, 313339-92-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SANOFI; NAZARE, Marc; Halland, Nis; Schmidt, Friedemann; Weiss, Tilo; Dietz, Uwe; Hofmeister, Armin; US2013/72493; (2013); A1;,
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 33332-25-1 as follows. Application In Synthesis of Methyl 5-chloropyrazine-2-carboxylate

A solution of methyl 5-chloropyrazine-2-carboxylate (1.0 g, 5.79 mmol) and morpholine (756 mg, 8.69 mmol) in DMSO (10 mL) was added K2CO3 (2.4 g, 17.4 mmol). The mixture was heated to 100C for 4 hours and then cooled to r.t. Water (20 mL) was added and the mixture was extracted with EA (20 mLx3).The combined organic phase was washed with water (20 mL) and brine (20 mL). It was then dried over anhydrous Na2SO4 and concentrated to give the desired product as a yellow solid (850 mg) which was used directly next step. ESI-MS m/z: 224.1 [M+H]+.

According to the analysis of related databases, 33332-25-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ENANTA PHARMACEUTICALS, INC.; SHOOK, Brian, C.; KIM, In, Jong; BLAISDELL, Thomas, P.; YU, Jianming; PANARESE, Joseph; LIN, Kai; RHODIN, Michael, H.J.; McALLISTER, Nicole, V.; OR, Yat, Sun; (447 pag.)WO2019/67864; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, 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 78342-42-4, Computed Properties of C9H16N2O2

To a solution of (25)-3,6-dimethoxy-2-(propan-2-yl)-2,5-dihydropyrazine (1.84 g, 9.99 mmol) in THF (50 mL) was added n-BuLi (6.0 mL, 2.5M in n-hexane) at -78 °C. The resulting solution was stirred for 30 mm at -78 °C. To this was added benzyl 4-[4-(bromomethyl)-2,3,5,6- tetrafluorophenyl]piperazine-1-carboxylate (4.60 g, 9.97 mmol) at -78 °C. The resulting solution was stirred for 2h at -78 °C. The reaction was then quenched by the addition of NH4C1 (sat., aq.) (40 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with brine (3 x 30 mL), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by reversed phase chromatography (Column: C18 silica gel; Mobile phase, A: water (containing 0.05percent TFA) and B: ACN (5percent to 75percent in 30 mm) to give benzyl 4-(4-[[(2R,55)-3,6-dimethoxy-5-(propan-2-yl)-2,5-dihydropyrazin-2-yl]methyl]-2, 3,5, 6-tetrafluorophenyl)piperazine- 1 -carboxylate as yellow oil. MS (ESI, m/z): 565 [M+H]t

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, (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FORMA THERAPEUTICS, INC.; ZABLOCKI, Mary-Margaret; GUERIN, David J.; NG, Pui Yee; WANG, Zhongguo; SHELEKHIN, Tatiana; CARAVELLA, Justin; LI, Hongbin; IOANNIDIS, Stephanos; (518 pag.)WO2019/32863; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

17231-51-5, name is 3-Amino-6-bromopyrazine-2-carbonitrile, 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: 3-Amino-6-bromopyrazine-2-carbonitrile

Step A Synthesis of 2-amino-3-cyano-5-(trimethylsilylethynyl)pyrazine as an intermediate A solution of 3.0 grams (0.015 mole) of 2-amino-3-cyano-5-bromopyrazine and 2.1 grams (0.021 mole) of trimethylsilylacetylene in 50 mL of acetonitrile is stirred, and 10.6 mL of triethylamine, 0.13 gram of copper iodide, and 0.29 gram of bis(triphenylphosphine)palladium(II) chloride are added in order. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about 20 hours. The reaction mixture is warmed to 70 C., where it is stirred for about 7.5 hours. After this time, the reaction mixture is concentrated under reduced pressure to a residue. The residue is dissolved in ethyl acetate, and the solution is washed with 50 mL of aqueous, dilute hydrochloric acid. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residue. The residue is subjected to column chromatography on silica gel. Elution is accomplished using tetrahydrofuran/methylene chloride combinations. The product-containing fractions are combined and concentrated under reduced pressure, yielding 2-amino-3-cyano-5-(trimethylsilylethynyl)pyrazine.

The synthetic route of 17231-51-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FMC Corporation; US5521190; (1996); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 24241-18-7, These common heterocyclic compound, 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, 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 stirred suspension of 2-amino-3,5-dibrompyrazine (427 g, 1688mmol) in water (6.4 L) / THF (482 mL), at rt was added bromacetaldehyde-diethylacetal (998 g, 5065 mmol) in one portion. After stirring under reflux for 4 h, the clear orange solution was stirred for an additional 15 h at rt. The suspension was filtered, and the remaining solid was washed with MeOH (2 L) and dried in vaccuo at 60 C to yield 6,8-dibromo-imidazo[1 ,2-a]pyrazine as an off-white solid (500 g, 107% with residual MeOH): 1H-NMR (300 MHz, d6-DMSO): delta =9.02 (s, 1 H), 8.23 (d, 1 H), 7.89 (d, 1 H) ppm. UPLC-MS: RT = 0.80 min; m/z 277.9 [MH+]; required MW = 276.9.

Statistics shows that 2-Amino-3,5-dibromopyrazine is playing an increasingly important role. we look forward to future research findings about 24241-18-7.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; SIEMEISTER, Gerhard; BADER, Benjamin; WENGNER, Antje, Margret; MUMBERG, Dominik; KOPPITZ, Marcus; KLAR, Ulrich; KROEMER, Guido; VITALE, Ilio; JEMAA, Mohamed; WO2014/20041; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem