Month: September 2021

Electric Literature of 23688-89-3, 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. 23688-89-3 name is 6-Chloropyrazine-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.

Intermediate 136-Ch[oro-N,N-dimethy[pyrazine-2-carboxamide A mixture of 6-ch[oropyrazine-2-carboxy[ic acid [CAS-RN: 23688-89-3] (510 mg,3.22 mmo[, 1.0 eq), dimethy[amine [CAS-RN: 124-40-3] (1.61 mL, 2M so[ution inTHF, 3.22 mmo[, 1.0 eq), HATU (1.47 g, 3.86 mmo[, 1 .2 eq) and DIPEA (1 .78 mL, 9.65 mmo[, 3.0 eq) was disso[ved in 15 mL DMF and stirred at rt overnight. The reaction mixture was partitioned between ethy[ acetate and water. The organic phase was washed with brine and separated by the use of a Whatman fi[ter. Thevo[ati[e components were removed in vacuo and the crude materia[ obtained was purified via preparative MPLC (Biotage Iso[era; 25 g SNAP cartridge: hexane/ethy[ acetate 8/2 -> hexane/ethy[ acetate 4/6) to give 330 mg (50% yie[d of theory) of the tit[e compound.UPLC-MS (Method 1): R = 0.67 mm; MS (EI0): m/z = 186 [M]÷.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Chloropyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; PRECHTL, Stefan; SIEMEISTER, Gerhard; WENGNER, Antje Margret; ACKERSTAFF, Jens; NOWAK-REPPEL, Katrin; BADER, Benjamin; LIENAU, Philip; STOeCKIGT, Detlef; WO2014/118186; (2014); 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. Recommanded Product: 313339-92-3

(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

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., Computed Properties of C8H11BrN4O

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

Electric Literature of 113305-94-5,Some common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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.

1 E. Benzyl-{4-[(Z)-3-(5-cyano-yrazin-2-ylamino)-3-methylsulfanyl-acryloyl]-35- dimethoxy-henyl}-carbamic acid tert-butyl esterA solution of 2-amino-5-cyanopyrazine (1.25 g, 5.2 mmol) in THE (10 mL) was added slowly to a stirred slurry of NaH (60% in mineral oil) (0.21 g, 5.2 mmol) in THE (17 mL)at 0C. The mixture was stirred for 30 minutes at 0C then a solution of benzyl-[4-(3,3- bis-methylsulfanyl-acryloyl)-3,5-dimethoxy-phenyl]-carbamic acid tert-butyl ester (1 .7 g, 3.48 mmol) in THE (7 mL) was added dropwise and the reaction mixture was heated to 80C for 12 hours. The solution was allowed to cool to room temperature then water (40 mL) was carefully added and the mixture extracted with EtOAc (3 x 25 mL). The combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure to leave a residue that was purified by column chromatography on neutral silica gel (60-120 mesh size) using 0-70% EtOAc/hexanes as the eluentto give thetitle compound (0.9 g, 46%).

The synthetic route of 113305-94-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ONCOTHYREON INC.; BOYLE, Robert, George; WALKER, David, Winter; BOYCE, Richard, Justin; PETERSON, Scott; FAROUZ, Francine; VO, Cong, Hung; WO2015/120390; (2015); 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. name: 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

These common heterocyclic compound, 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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. Computed Properties of C6H6N2O2

A solution of the product of Example 83A (6.91 g, 50 mmol) in THF (Aldrich, anhydrous, 150 mL) was cooled down to -78° C. and a solution of LiAlH4 (Aldrich, 1.898 g, 50.0 mmol) in THF (50 mL) was added slowly via an additional funnel. The mixture was stirred at -78° C. under N2 for 1 hour, and then it was then carefully and slowly quenched with HOAc (Aldrich, 10 mL) at -70° C. The mixture was slowly warmed up to ambient temperature and stirred for 10 hours. After being concentrated, the residue was stirred with HCl (2N, 15 mL) in CH2Cl2 (300 mL) for 20 minutes and then filtered through diatomaceous earth to remove solid inorganic salt. The organic filtrate solution was concentrated and the residue was dissolved in EtOAc (100 mL) and filtered through diatomaceous earth again. The organic filtrate solution was concentrated to give the titled compound. 1H NMR (300 MHz, DMSO-d6) delta 8.91 (dd, 1H), 8.94 (d, 1H), 9.12 (d, J=1.6 Hz, 1H), 10.08 (s, 1H) ppm; MS (DCI/NH3) m/z 109 (M+H)+.

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

Reference:
Patent; ABBOTT LABORATORIES; US2009/306096; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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

1057216-55-3, name is 2-Chloro-5-iodopyrazine, 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. SDS of cas: 1057216-55-3

Intermediate 31 (350 mg, 1.05 mmol), 2-chloro-5-iodopyrazine (252 mg, 1.05 mmol), 2M aqueous sodium carbonate solution (1.58 mL, 3.16 mmol) and anhydrous DMSO (5 mL) were charged to a sealed tube. The mixture was degassed by bubbling with nitrogen for 5 minutes before the addition of tetrakis(triphenylphosphine)20 palladium(0) (61 mg, 0.05 mmol). The reaction mixture was sealed under nitrogen andstirred at 110C for 1 h. The mixture was diluted with water (40 mL) and extracted with EtOAc (3 x 20 mL). The organic phase was washed with saturated aqueous sodium bicarbonate solution (2 x 10 mL) followed by brine (10 mL), then dried over sodium sulfate and concentrated under vacuum. The residue was purified by FCC, eluting with17-80% EtOAc in heptane, to afford the title compound (285 mg, 54% at 80% purity) as an off white solid. oH (500 MHz, CDC13) 8.73-8.64 (m, 2H), 8.63-8.59 (m, 1H), 7.92 (s, 2H), 7.33-7.27 (m, 1H), 7.17 (d, J8.2 Hz, 1H), 7.15-7.07 (m, 1H), 7.00 (d, J6.6 Hz, 1H),6.67 (t, J73.5 Hz, 1H), 4.36 (s, 2H), 2.60 (s, 3H). Method C HPLC-MS: MH+ m/z 401,

The synthetic route of 1057216-55-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UCB PHARMA S.A.; BENTLEY, Jonathan Mark; BROOKINGS, Daniel Christopher; BROWN, Julien Alistair; CAIN, Thomas Paul; CHOVATIA, Praful Tulshi; FOLEY, Anne Marie; GALLIMORE, Ellen Olivia; GLEAVE, Laura Jane; HEIFETZ, Alexander; HORSLEY, Helen Tracey; HUTCHINGS, Martin Clive; JACKSON, Victoria Elizabeth; JOHNSON, James Andrew; JOHNSTONE, Craig; KROEPLIEN, Boris; LECOMTE, Fabien Claude; LEIGH, Deborah; LOWE, Martin Alexander; MADDEN, James; PORTER, John Robert; QUINCEY, Joanna Rachel; REED, Laura Claire; REUBERSON, James Thomas; RICHARDSON, Anthony John; RICHARDSON, Sarah Emily; SELBY, Matthew Duncan; SHAW, Michael Alan; ZHU, Zhaoning; WO2014/9295; (2014); 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. 56423-63-3, name is 2-Bromopyrazine, A new synthetic method of this compound is introduced below., name: 2-Bromopyrazine

n-BuLi (25.4 ml_, 63.5 mmol, 2.5 M in hexane) was added drop wise to a -78 C solution of 2-bromopyrazine (10.1 g, 63.5 mmol) in toluene (150 ml_) under N2. After 10 min at -78 C, a solution of N-cyclobutylidene-2-methylpropane-2-sulfinamide (Preparation 50, 10.0 g, 57.71 mmol) in toluene (50 ml_) was added slowly. The resulting dark red solution was stirred for 1 hr at -78 C. The reaction was quenched by the addition of sat. NH4CI solution (10 ml_) and the reaction mixture dried (MgS04), filtered and concentrated in vacuo to give a brown oil. The crude product was purified by column chromatography on silica gel eluting with pet. Ether: EtOAc (100:0 to 0: 100) to MeOH: EtOAc (9:91 ) to afford the title compound as a yellow oil, 4.0 g, 27%. 1H NMR (400 MHz, CDCI3): delta 1 .21 (s, 9H), 1.86-1 .96 (m, 1 H), 2.08-2.19 (m, 1 H), 2.58-2.78 (m, 4H), 3.62-3.75 (br s, 1 H), 8.49 (d, 1 H), 8.56 (dd, 1 H), 8.80 (d, 1 H). LCMS m/z = 254 [M+H]+

The synthetic route of 56423-63-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; CASIMIRO-GARCIA, Agustin; STROHBACH, Joseph Walter; HEPWORTH, David; LOVERING, Frank Eldridge; CHOI, Chulho; ALLAIS, Christophe Philippe; WRIGHT, Stephen Wayne; (213 pag.)WO2018/11681; (2018); 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. 6863-73-6, name is 3-Chloropyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 6863-73-6

Example A3 8-Chloro-imidazo[1,2-a]pyrazine Bromoacetaldehyde diethyl acetal (17.4 ml, 115.8 mmol) was added dropwise to a 48% aqueous solution of hydrobromic acid (4.45 ml, 38.6 mmol) at RT. The mixture was stirred at reflux temperature for 2 h. and then poured onto a suspension of sodium hydrogen carbonate (74.5 g, 0.88 mol) in isopropanol (220 ml). The mixture was stirred for a further 30 min. and then filtered off. 3-Chloro-pyrazin-2-ylamine (5 g, 38.6 mmol) was added to the filtrate and the mixture was stirred at 85 C. for 4 h. The solvent was evaporated in vacuo and the crude product suspended in a saturated solution of sodium hydrogen carbonate and extracted with DCM. The organic layer was dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was precipitated from Et2O to yield intermediate 3 (4.1 g, 70%) as a brown solid which was used in the next step without further purification.

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 6863-73-6.

Reference:
Patent; Janssen Pharmaceutica NV; US2012/329792; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem