Tag: M.W=100-200

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

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

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

Application of 356783-16-9, The chemical industry reduces the impact on the environment during synthesis 356783-16-9, name is 3,6-Dichloropyrazine-2-carbonitrile, I believe this compound will play a more active role in future production and life.

To a solution of 3,6-dichloropyrazine-2-carbonitrile (1.088 g, 6.25 mmol) in toluene (12 mL) at 0 C. was added dropwise methyl hydrazine (362 muL, 6.88 mmol). Reaction mixture was stirred for 3 hours at 0 C. LCMS shows no starting material. Reaction mixture was concentrated and purified by CombiFlash (120 g Gold, 10-45% EtOAc/Hex) to give impure product. Crystallized from hot acetone/hexane to give two crops of 5-chloro-1-methyl-1H-pyrazolo[3,4-b]pyrazin-3-amine. LCMS-ESI+: calc’d for C6H7ClN5: 184.0 (M+H)+; found: 184.2 (M+H)+.

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, 3,6-Dichloropyrazine-2-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Gilead Sciences, Inc.; Cai, Zhenhong R.; Guo, Hongyan; Ji, Mingzhe; Jin, Haolun; Lee, Amy; McFadden, Ryan; Mitchell, Michael L.; Munoz, Manuel; Pyun, Hyung-Jung; Xu, Lianhong; Yang, Hong; (272 pag.)US2018/118734; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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 33332-25-1 as follows. Computed Properties of C6H5ClN2O2

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

6164-79-0, Adding a certain compound to certain chemical reactions, such as: 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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 6164-79-0.

Methyl 3-oxo-3-(pyrazin-2-yl)propanoate: To a stirred solution of sodium methoxide (25% in MeOH, 27.54 mL, 72.4 mmol, 1 eq) in 90 mL of toluene at 110 C. in a 3-neck flask attached with a mechanical stirrer, condenser and dropping funnel was added a solution of methylpyrazine-2-carboxylate (10 g, 72.4 mmol, 1 eq) in 115 mL of methyl acetate, dropwise, over a period of ?35-40 min. A yellow precipitate was formed. Stirring was continued at 110 C. for 3 hrs. The reaction was cooled and the yellow precipitate was filtered and washed with a small quantity of toluene. This solid was taken into 200 mL of saturated ammonium chloride and 400 mL of EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give 6.52 g (50%) of methyl 3-oxo-3-(pyrazin-2-yl)propanoate as a yellow solid.

According to the analysis of related databases, 6164-79-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hoffmann-La Roche Inc.; Bhagirath, Niala; Brameld, Kenneth Albert; Kennedy-Smith, Joshua; US2013/90333; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 33332-25-1, 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. 33332-25-1 name is Methyl 5-chloropyrazine-2-carboxylate, 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.

Combine 5-CHLOROPYRAZINE-2-CARBOXYLIC acid methyl ester (626 mg, 3.64 mmol), phenylboronic acid (666 mg, 5.45 mmol), cesium fluoride (55 mg, 0.36 mmol) and NA2CO3 (964 mg, 9.09 mmol) in DMF (5 mL) and water (5 mL) with stirring. Place the hetereogeneous reaction mixture, open to the air, in an oil bath maintained at 80C. After 5 minutes of heating, add Pd (OAC) 2 (81 mg 0.36 mmol) in one portion and stir until reaction turns black. Cool the reaction to room temperature, dilute with ethyl acetate, and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over MGS04, filter and evaporate. Purification by flash column chromatography yields 2-phenylpyrimidine-5-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1M NAOH. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCI and extract with ethyl acetate. Evaporation of the solvent yields 63 mg (8%) of the title COMPOUND. H NMR (DMSO): 9.37 (s, 1H), 9.21 (s, 1H), 8.23-8. 21 (m, 2H), 7.57-7. 77 (m, 3H).

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

Reference:
Patent; ELI LILLY AND COMPANY; WO2004/94382; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 6863-73-6, A common heterocyclic compound, 6863-73-6, name is 3-Chloropyrazin-2-amine, molecular formula is C4H4ClN3, 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.

Benzyl alcohol (4.55 g, 42.15 mmol) was added under an inert atmosphere dropwise to a suspension of sodium hydride (1. 01 g, 42.13 mmol, 80%) in N-methylpyrrolidinone. Stirring of the reaction mixture was continued for 30 min. 2-Amino-3-chloropyrazine (Compound I in Scheme 1, 5.0 g, 38.6 mmol) was then added in incrememtal portions and the resultant mixture was heated at 80 C for 24 h. The reaction mixture was subsequently cooled and water (200 mL) was added. The aqueous solution was extracted with EtOAc (2 x 40 mL). The combined organic layers were washed with water (2 x 100 mL), dried (Mg04), and concentrated under reduced pressure to obtain a light brown residue. Addition of cold water to the residue, triggered crystallization of the desired product. The crystals were collected and dried over P2O5 (6.33 g, 82%). 1H-NMR (CDCl3) No. 7. 54 (d, J 3.1 Hz, 1H), 7.45-7. 32 (m, 6H), 5. 38 (s, 2H), 4. 78 (br s, 2H); MS (ESI) 202.2 ([M+H] +)

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; CARDIOME PHARMA CORPORATION; WO2005/34837; (2005); A2;,
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 14508-49-7 as follows. Application In Synthesis of 2-Chloropyrazine

A mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), prepared from 2-chloropyrazine and hydrazine using a procedure analogous to that described in the literature (P. J. Nelson and K. T. Potts, J. Org. Chem. 1962, 27, 3243, except that the crude product was extracted into 10% methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate followed by 10% methanol in dichloromethane), TFA (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140 C. with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted with ethyl acetate (3×), washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexane:ethyl acetate, then 100% ethyl acetate) afforded the title compound as a solid (861 mg). 1H NMR (500 MHz, CDCl3) delta 8.17-8.20 (m, 2H), 9.54 (s, 1H). LC/MS (M+1) 189.

According to the analysis of related databases, 14508-49-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Merck Sharp & Dohme Corp.; Edmondson, Scott D.; Fisher, Michael H.; Kim, Dooseop; Maccoss, Malcolm; Parmee, Emma R.; Weber, Ann E.; Xu, Jinyou; US2015/359793; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem