Category: 33332-25-1

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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., category: Pyrazines

A 250ml RB flask is charged with R-7 (5.4 g, 28.99 mmol) in 100 mL of NMP. R-8 (5.00 g, 28.99 mmol) is added followed by triethylamine (4.85 ml, 34.79 mmol). The reaction is heated to 60 C under nitrogen overnight. The reaction is cooled to room temperature, poured into ice water and the precipitated 1-76 (8.60 g) is isolated by filtration; m/z 323.4 [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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BARTOLOZZI, Alessandra; BOSANAC, Todd; CHEN, Zhidong; DE LOMBAERT, Stephane; HUBER, John; LO, Ho Yin; LOKE, Pui Leng; LIU, Weimin; MORWICK, Tina Marie; OLAGUE, Alan; RIETHER, Doris; TYE, Heather; WU, Lifen; ZINDELL, Renee; WO2012/24150; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature 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

Synthetic Route of 33332-25-1, A common heterocyclic compound, 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, molecular formula is C6H5ClN2O2, 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 30 2- (3-CHLORO-4-METHANESULFONYL-PHENYL)-3-CYCLOPENTYL-N-(5-METHYLSULFANYLMETHYL- PYRAZIN-2-YL)-PROPIONAMIDE [000205] A solution of methyl 5-chloropyrazine-2-carboxylate (5.00 g, 28.97 mmol) in acetonitrile (290 ML) was treated with a fresh bottle of silver (I) fluoride (11.00 g, 86.70 mmol). The reaction setup was covered with aluminum foil, and the reaction mixture was heated at reflux overnight. The mixture was filtered through a pad of celite, and the pad of celite was rinsed with acetonitrile. The filtrate was then concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 25% ethyl acetate/hexanes) afforded 5-fluoro-pyrazine-2-carboxylic acid methyl ester (2.98 g, 66%) an off-white solid upon cooling to 0C. An analytical sample was obtained by trituration with petroleum ether to afford 5-fluoro-pyrazine-2-carboxylic acid methyl ester as a white crystalline solid: mp 55.6-56. 7C, EI-HRMS m/e calcd for C6HSFN202 (M 156.0335, found 156.0331.

The synthetic route of 33332-25-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2004/52869; (2004); 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: Methyl 5-chloropyrazine-2-carboxylate

Preparation of 5-Chloropyrazine-2-carboxylic acid To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added methyl 5-chloropyrazine-2-carboxylate (1.0 eq) and tetrahydrofuran (4.92 vols) under a nitrogen atmosphere. The reaction mixture was agitated until all the solid had dissolved, then filtered into a second flask. Water (8.65 vols) was added to the reaction mixture and the mixture agitated for approximately 15 minutes. Potassium carbonate (2.1 eq) was added to the reaction mixture and the mixture agitated for 16 hours at 20-25 C. Then 32% w/w hydrochloric acid (3.76 eq) was added over 3 hours in small portions, keeping the reaction temperature 20-25 C., to a pH end point of pH2.2. The resultant slurry was heated to approximately 35-40 C. and then distilled under vacuum at this temperature distilling approximately 5.3 vols, to a final volume of approximately 9.3 vols. The mixture was then cooled to 20-25 C. over at least 2 hours, agitated for 10 hours at this temperature and then filtered. The solid was washed with water (2.8 vols), and the wet product produced dried at 35 C. in a vacuum oven. The desired product was obtained as a solid (corrected yield 91%) 1H NMR delta (400 MHz CDCl3): 7.20 (1H, bs), 8.72 (1H, s), 9.21-9.21 (1H, m); m/z 157 (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; AstraZeneca AB; US2010/210621; (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. Formula: C6H5ClN2O2

Synthesis of 2,3<5,6-Tetrahydro-ri,2'1bipyrazinyl-4,5'-dicarboxylic acid 4-tert-butyl ester (Intermediate 1-3.1)Step 1: Synthesis of 2,3,5,6-Tetrahydro-ri,2'lbipyrazinyl-4,5'-dicarboxylic acid 4-tert- butyl ester 5'-methyl ester (R8)A 250ml RB flask is charged with R7 (2.8 g, 16.11 mmol) in 60mL of NMP. R6 (3.0 g, 16.11 mmol) is added followed by triethylamine (2.7 ml, 19.33 mmol). The reaction is warmed to 60 C under nitrogen and stirred overnight. After 18 h, the reaction is cooled to room temperature, poured into ice water and the resulting solid R8 is isolated by filtration and used without further purification. (5.0 g) 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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BARTOLOZZI, Alessandra; BOSANAC, Todd; CHEN, Zhidong; DE LOMBAERT, Stephane; DINES, Jonathon Alan; HUBER, John, D.; LIU, Weimin; LO, Ho Yin; LOKE, Pui Leng; MORWICK, Tina Marie; NEMOTO, Peter Allen; OLAGUE, Alan; RIETHER, Doris; TYE, Heather; WU, Lifen; ZINDELL, Renee, M.; WO2012/27322; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 33332-25-1, name is Methyl 5-chloropyrazine-2-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. Application In Synthesis of Methyl 5-chloropyrazine-2-carboxylate

To a solution of methyl-5-chloropyrazine-2-carboxylate (120 mg, 0.70 mmol) in a mixture of acetonitrile (2 mL) and DMF (1 mL) was added lithium chloride (295 mg, 6.95 mmol). The suspension was heated to 160C for 5 mins in a Smith creator microwave after which time the reaction was diluted with water (10 mL). Saturated sodium bicarbonate solution (20 mL) was added and the aqueous layered extracted twice with ethyl acetate (30 mL). The combined organics were discarded and the aqueous layer adjusted to pH 4 with IN hydrochloric acid. The aqueous phase was extracted twice with ethyl acetate (20 mL) and the combined organics washed with water (2 x 20 mL), brine (10 mL) and dried (MgSO4). The volatiles were removed to give the title compound as a colourless solid (68 mg). 1H NMR delta (CDCl3): 7.20 (IH, br s), 8.72 (IH, s), 9.21 – 9.21 (IH, m); m/z 157 (M-H)+.

The synthetic route of Methyl 5-chloropyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/7041; (2007); 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 33332-25-1

Sodium hydride (60% dispersion in mineral oil) (6.4 g, 0.16 mol) was added portionwise to a solution of 7-hydroxy-1, 2,4, 5-tetrahydro-benzo [DIAZEPINE-3-CARBOXYLIC acid TERT-BUTYL ester (PCT Int. APPL. (2002), WO 02/40471) (40 g, 0.15 mol) in dry dimethylformamide (200 ml) cooled to 5 C over 15 minutes. After 15 minutes, the mixture was allowed to warm to room temperature and stirred for 60 minutes. The mixture was cooled in an ice-water bath and methyl 5-chloro-2-pyrazinecarboxylate (31.2 g, 0.18 mol) was added portionwise. The mixture was allowed to warm to room temperature and stirred for 18 hours. The mixture was poured onto water (500 mi) and ice (500 ml) and stirred until the ice had melted. The resulting solid was collected by filtration, washed with water and dissolved in ethyl acetate (1500 ML). The ethyl acetate layer was washed with brine (200 ML), dried under sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography eluting with a mixture of ethyl acetate: hexane (1: 2) to afford the title compound (35.07 g).

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; GLAXO GROUP LIMITED; WO2004/56369; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 33332-25-1, 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.

(5-chloropyrazin-2-yl)methyl methanesulfonate; [00369] To a solution of 5-chloropyrazine-2-carboxylic acid (3.21 g, 20.3 mmol) in diethyl ether (20 mL) and methanol (20.0 mL) was added a 2M solution in diethyl ether of trimethylsilyldiazomethane (20.3 mL, 40.5 mmol). A vigorous bubbling was observed initially, and LCMS after 30 minutes indicated that the reaction was complete.Concentration of the reaction mixture afforded methyl 5-chloropyrazine-2-carboxylate (3.53 g, 20.5 mmol, 101% yield) as a tan solid. This material was shown to be >95% pure by NMR analysis and was used in the subsequent step without any purification. lH NMR (400 MHz, CDC13) delta (ppm): 9.09 (s, 1H), 8.70 (s, 1H), 4.04 (s, 3H).[00370] To a 0 C solution of methyl 5-chloropyrazine-2-carboxylate (3.50 g, 20.3 mmol) in tetrahydrofuran (101 mL) was added a 1M solution in tetrahydrofuran of diisobutylaluminum hydride (42.6 mL, 42.6 mmol). The reaction was stirred at 0 C for 2 hours, after which it was quenched by the addition of methanol (2 mL). To this mixture was added saturated sodium-potassium tartrate solution, and the resulting reaction mixture was extracted with ethyl acetate (3 x 100 mL), dried (sodium sulfate), filtered and concentrated to brown residue. Purification was achieved by column chromatography on silica gel (Luknova 120 g, 20 mL/min) using 30 to 100% ethyl acetate in hexanes over 60 minutes to afford (5- chloropyrazin-2-yl)methanol (1.45 g, 10.0 mmol, 50 % yield) as a tan solid. NMR (400 MHz, CDC13) a (ppm): 8.56 (s, 1H), 8.45 (s, 1H), 4.84 (s, 3H), 2.79 (br. s, 1H).[00371] To a 0 C solution of (5-chloropyrazin-2-yl)methanol (648 mg, 4.48 mmol) in dichloromethane (12 mL) was added triethylamine (1.87 mL, 13.5 mmol) followed by dropwise addition of methanesulfonyl chloride (0.699 mL, 8.97 mmol). After 20 minutes, analysis by LCMS indicated the complete conversion to the mesylate product. The reaction mixture was concentrated to afford (5-chloropyrazin-2-yl)methyl methanesulfonate (787 mg, 3.53 mmol, 79% yield) as an oil. The material was used crude in the next step without further purification.

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; IRONWOOD PHARMACEUTICALS, INC.; HUDSON, Colleen; BARDEN, Timothy, C.; JIA, James; MERMERIAN, Ara; PENG, Bo; YANG, Jane; YU, Xiang, Y.; SPROTT, Kevin; WO2012/88469; (2012); 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: 33332-25-1

Diisobutylaluminium hydride (1.0 M in toluene; 6.4 mL, 6.40 mmol) was added dropwise to a cooled solution of methyl 5-chloropyrazine-2-carboxylate (690 mg, 4.00 mmol) in THF (13.6 mL) at -55 C. The reaction was stirred under these conditions for 1 hour and then quenched by addition of saturated aqueous NH4C1 (25 mL) and EtOAc (25 mL). An emulsion formed and 2N aqueous HC1 was added to clear the emulsion (5 mL). The layers were separated, and the aqueous layer was extracted with EtOAc. The organic layerwas washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in heptane. Product fractions were evaporated to dryness to afford 5-chloropyrazine-2-carbaldehyde (385 mg, 68%) as a beige solid. ?H NMR (500 MHz, CDC13, 27 C) 8.75 (1H, d), 8.96 (1H, d), 10.15 (1H, d).

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; ASTRAZENECA AB; SCOTT, James, Stewart; MOSS, Thomas, Andrew; YANG, Bin; VARNES, Jeffrey, Gilbert; O’DONOVAN, Daniel, Hillebrand; NISSINK, Johannes, Wilhelmus, Maria; HUGHES, Samantha, Jayne; BARLAAM, Bernard, Christophe; WU, Dedong; BROO, Dan, Anders; (224 pag.)WO2018/19793; (2018); 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Quality Control of Methyl 5-chloropyrazine-2-carboxylate

Diisobutylaluminium hydride (1.0 M in toluene; 6.4 mL, 6.40 mmol) was added dropwise to a cooled solution of methyl 5-chloropyrazine-2-carboxylate (690 mg, 4.00 mmol) in THF (13.6 mL) at -55 C. The reaction was stirred under these conditions for 1 hour and then quenched by addition of saturated aqueous NH4C1 (25 mL) and EtOAc (25 mL). An emulsion formed and 2N aqueous HC1 was added to clear the emulsion (5 mL). The layers were separated, and the aqueous layer was extracted with EtOAc. The organic layerwas washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in heptane. Product fractions were evaporated to dryness to afford 5-chloropyrazine-2-carbaldehyde (385 mg, 68%) as a beige solid. ?H NMR (500 MHz, CDC13, 27 C) 8.75 (1H, d), 8.96 (1H, d), 10.15 (1H, d).

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; ASTRAZENECA AB; SCOTT, James, Stewart; MOSS, Thomas, Andrew; YANG, Bin; VARNES, Jeffrey, Gilbert; O’DONOVAN, Daniel, Hillebrand; NISSINK, Johannes, Wilhelmus, Maria; HUGHES, Samantha, Jayne; BARLAAM, Bernard, Christophe; WU, Dedong; BROO, Dan, Anders; (224 pag.)WO2018/19793; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem