Category: 912773-21-8

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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, A new synthetic method of this compound is introduced below., Computed Properties of C4H2BrClN2

Example 19 1-(5-Chloropyrazin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (49) To a stirred suspension of copper powder (3.0 g, 46.51 mmol) in DMSO (10 mL) was added ethyl 2-bromo-2,2-difluoroacetate (4.7 g, 23.15 mmol) at RT, and the mixture was stirred at RT for 1 h under inert atmosphere. A solution of 2-bromo-5-chloropyrazine (3.0 g, 15.54 mmol) in DMSO (20 mL) was added to the reaction mixture, and stirring was continued for another 16 h at RT. After the consumption of starting material (by TLC), the reaction mixture was diluted with aq NH4Cl solution (40 mL), filtered through a Celite pad and washed with CH2Cl2 (3*25 mL). The collected filtrate was washed with H2O (30 mL) and brine (30 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude material. Purification by column chromatography (eluting with 20% EtOAc/hexane) afforded ester AS (1.12 g, 4.73 mmol, 31%) as a liquid. 1H NMR (500 MHz, CDCl3): delta 8.78 (s, 1H), 8.62 (s, 1H), 4.38 (q, J=7.0 Hz, 2H), 1.37 (t, J=7.0 Hz, 3H).

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; VIAMET PHARMACEUTICALS, INC.; US2012/329802; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 912773-21-8, 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 912773-21-8 as follows.

A mixture of 2-bromo-5-chloro-pyrazine (1 g, 5.17 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-[(lS)-2,2,2-trifluoro-l- methyl -ethoxy ] pyridine (1.73 g, 5.17 mmol), CS2CO3 (3.37 g, 10.34 mmol) and Pd(dppf)Cl2 (567.41 mg, 0.78 mmol) in l,4-Dioxane (100 mL) and Water (10 mL) was stirred at 55 C under N2 for 5 hours. From LCMS, desired MS was observed and no starting material was remained. The solution was cooled to room temperature and concentrated to give a residue. To the residue was added water (50 mL), extracted with EtOAc (50 mL x 2). The combined organic phase was washed with water (50 mL), brine (50 mL x 2), dried over anhydrous Na2S04, filtered and concentrated to give the crude product. The crude product was purified by flash chromatography column on silica gel (EtOAc in PE = 0% to 5%) to give the product (1.4 g,4.35 mmol, 84% yield) as a solid. ‘H NMR (DMSO-c, 400MHz) 5H= 9.18 (s, 1H), 8.91 – 8.74 (m, 2H), 8.46 (dd, 1H), 6.05 – 5.99 (m, 1H), 1.53 (d, 3H).

According to the analysis of related databases, 912773-21-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; MARTINEZ BOTELLA, Gabriel; REDDY, Kiran; WITTMANN, Marion; (0 pag.)WO2019/232209; (2019); 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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Bromo-5-chloropyrazine

Intermediate 30a and 30b: N-[(1S,2S)-2-[(5-Bromopyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 30a) and N-[(1S,2S)-2-[(5-Chloropyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 30b) A solution of N-[(1S,2S)-2-aminocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 4; 1.00 g, 3.25 mmol), 2-bromo-5-chloropyrazine (CAS number 912773-21-8; 0.691 g, 3.57 mmol) and DIPEA (1.7 ml, 9.75 mmol) in DMSO (11 ml) was subjected to microwave irradiation at 140 C. for 3 hours. The reaction was partitioned between ethyl acetate and water, washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. This was then purified by column chromatography (silica, 0-100% ethyl acetate/petrol then 0-20% methanol ethyl acetate) to afford title compound as a mixture of both products Example 112 N-[(1S,2S)-2-[(5-Cyclopropylpyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide A mixture of N-[(1S,2S)-2-[(5-bromopyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide and N-[(1S,2S)-2-[(5-chloropyrazin-2-yl)amino]cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 30a and 30b; 100 mg, 0.23 mmol), cyclopropylboronic acid (CAS number 411235-57-9; 60 mg, 0.70 mmol), sodium carbonate (aq. 2 M, 350 mul, 0.70 mmol) and tetrakis(triphenylphosphine)palladium (27 mg, 0.023 mmol) in 1,4-dioxane (778 mul) was sealed, purged and evacuated with nitrogen and then subjected to microwave irradiation at 100 C. for 1 hour. To this was then added further cyclopropylboronic acid (CAS number 411235-57-9; 60 mg, 0.70 mmol) and tetrakis(triphenylphosphine)palladium (27 mg, 0.023 mmol). The reaction was sealed, purged and evacuated with nitrogen and again subjected to microwave irradiation at 140 C. for 20 minutes. The reaction was partitioned between ethyl acetate and water, washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) and then purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% formic acid) and further purified by column chromatography (basic silica, 0-100% ethyl acetate/petrol) to afford the title compound. 1H NMR (400 MHz, DCM-d2) delta ppm 0.77-0.92 (m, 4H), 1.40-1.60 (m, 2H), 1.68-1.94 (m, 3H), 2.14-2.29 (m, 2H), 3.80-3.91 (m, 1H), 3.99-4.10 (m, 1H), 6.65-6.73 (m, 1H), 7.43-7.59 (m, 4H), 7.64 (s, 2H), 7.68-7.72 (m, 1H), 7.74-7.78 (m, 1H) and 7.84 (br. s., 1H). MS ES+: 390

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 912773-21-8.

Reference:
Patent; Takeda Pharmaceutical Company Limited; Fieldhouse, Charlotte; Glen, Angela; Maine, Stephanie; Fujimoto, Tatsuhiko; Robinson, John Stephen; US2015/232460; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 912773-21-8, These common heterocyclic compound, 912773-21-8, name is 2-Bromo-5-chloropyrazine, 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.

N2 was bubbled through a solution of the product from step 1 (0.37 mmol) in toluene for 30 min. Separately, a flask was charged with 2-bromo-5-chloropyrazine (108 mg, 0.56 mmol), (Ph3P)4Pd (21.5 mg, 0.19 mmol) and copper(I) iodide (7.1 mg, 0.037 mmol), then sealed evacuated and purged with N2 thrice. The toluene solution was inhjected in to the flask and the solution stirred at 100 C for 3 h 15 min. The cooled solution was concentrated in vacuo to ~1/2 volume. FCC (5-40% EtOAc in cyclohexane) gave the title compound as a solid (97 mg). LCMS (Method A) 4.66 min, ES+ 476 [M+1]+.

Statistics shows that 2-Bromo-5-chloropyrazine is playing an increasingly important role. we look forward to future research findings about 912773-21-8.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BRONNER, Sarah M.; CRAWFORD, James J.; CRIDLAND, Andrew; CYR, Patrick; FAUBER, Benjamin; GANCIA, Emanuela; GOBBI, Alberto; HURLEY, Christopher; KILLEN, Jonathan; LEE, Wendy; RENE, Olivier; VAN NIEL, Monique Bodil; WARD, Stuart; WINSHIP, Paul; ZBIEG, Jason; (439 pag.)WO2018/83105; (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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Bromo-5-chloropyrazine

A mixture of Pd(dppf)Cl2 (15.13 g, 20.68 mmol), CS2CO3 (269.49 g, 827.17 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-(2,2,2- trifluoroethoxy)pyridine (141.18 g, 439.69 mmol) and 2-bromo-5-chloro-pyrazine (80 g, 413.59 mmol) in l,4-Dioxane (1 L) and Water (150 mL) under N2 was stirred at 35 C for 2 hours. After cooling to room temperature, to the mixture was added water (300 mL) and the mixture was filtered through Celite. After separating, the organic phase was washed with brine (300 mL), dried over anhydrous Na2S04, filtered and concentrated to give the crude product. The crude product was re-dissolved in EA/PE = 1/3 (500 mL) and then filtered through silica gel mat. The cake was washed with EA/PE = 1/3 (500 mL). The combined organic phase was concentrated to give a residue as oil. To the oil was added PE (500 mL) slowly and some solid was obtained. The solid was collected and dried in oven to give the product (100 g, 242.4 mmol, 58% yield) as a solid. LCMS Rt= 1.28 min in 2.0 min chromatography, 10-80AB, MS ESI calcd. for C11H7CIF4N3O [M+H]+308.0, found 307.9.

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; PRAXIS PRECISION MEDICINES, INC.; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; MARTINEZ BOTELLA, Gabriel; REDDY, Kiran; WITTMANN, Marion; (0 pag.)WO2019/232209; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference 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 suspension of copper (0) powder (244 g, 3877 mmol) in DMSO (5 L) was added ethyl 2-bromo-2,2-difluoroacetate (394 g, 1939 mmol) at RT. The reaction mixture was stirred at RT for 1 h and 2-bromo-5-chloropyrazine (Shanghai Fchemicals Technology Co., Ltd., Shanghai, China) (250 g, 1292 mmol) was added in portion-wise manner. The reaction mixture was stirred at RT for 3 h, and quenched with sat’d solution of ammonium chloride (2.0 L). The mixture was filtered through a celite pad and the filtrate was extracted with ethyl acetate (2 x 2 L). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0 – 2% ethyl acetate in hexanes) to afford 11a (215 g, 70% yield) as a viscous colorless liquid. 1H NMR (400 MHz, DMSO-d6) _ 9.05 (d, J = 1.4 Hz, 1H), 8.98 (dd, J = 1.4, 0.7 Hz, 1H), 4.39- 4.34 (m, 2H), 1.24 (t, J = 7.1 Hz, 3H).

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; AMGEN INC.; ALLEN, Jennifer R.; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Ning; FROHN, Michael J.; FU, Zice; LIU, Longbin; LIU, Qingyian; PETTUS, Liping H.; QIAN, Wenyuan; REEVES, Corey; SIEGMUND, Aaron C.; (362 pag.)WO2018/112094; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 912773-21-8, name is 2-Bromo-5-chloropyrazine, 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 912773-21-8, Application In Synthesis of 2-Bromo-5-chloropyrazine

A mixture of 2-bromo-5-chloro-pyrazine (229.4 mg, 1.19 mmol), [5-fluoro-6-(2,2,2- trifluoro-1-methyl-ethoxy)-3-pyridyl]boronic acid (300 mg, 1.19 mmol), Pd(dppf)Cl2 (130.16 mg, 0.18 mmol) and CS2CO3 (772.77 mg, 2.37 mmol) in 1,4-dioxane (10 mL) and water (1 mL) was stirred at 60 C for 5 hours under N2. After cooling to r.t., the mixture was diluted with _0 (30 mL), and the mixture was extracted with EtOAc (50 mL x 2). The combined organic phase was washed with water (20 mL x 2) and brine (20 mL), dried over Na2S04, filtered and concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 1% to 3% ) to give the product (210 mg, 0.64 mmol) as a solid. The product was analyzed by SFC to show two peaks (Peak 1: Rt = 2.02 min, Peak 2: Rt = 2.28 min). Method: Column: Chiralpak AD-3 150 x 4.6mm I.D, 3_ Mobile phase: A: C02 B:ethanol (0.05% DEA), Gradient: from 5% to 40% of B in 5 min and hold 40% for 2.5 min, then 5% of B for 2.5 min Flow rate: 2.5mL/min Column temp.: 35 C. 1H NMR (400MHz CDC13) _ = 8.77 (d, 1H), 8.65 (d, 1H), 8.53 (d, 1H), 8.08 (dd, 1H), 5.95 – 5.85 (m, 1H), 1.63 -1.48 (m, 3H). LCMS Rt = 0.92 min in 1.5 min chromatography, 5-95AB, purity 98.54%, MS ESI calcd. for Ci2H9ClF4N30 [M+H]+ 322.0, found 321.9

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; REDDY, Kiran; MARTINEZ BOTELLA, Gabriel; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; (364 pag.)WO2018/98499; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 912773-21-8, name is 2-Bromo-5-chloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 912773-21-8

To a suspension of copper (0) powder (244 g, 3880 mmol) in DMSO (5 L) was added ethyl 2-bromo-2,2-difluoroacetate (394 g, 1940 mmol) at room temperature. The reaction mixture was stirred at room temperature for 1 hour and 2-bromo-5-chloropyrazine (Shanghai Fchemicals Technology Co., Ltd., Shanghai, China) (250 g, 1290 mmol) was added in portion-wise manner. The reaction mixture was stirred at room temperature for 3 hours, then quenched with sat’d solution of ammonium chloride (2.0 L). The mixture was filtered through a celite pad and the filtrate was extracted with ethyl acetate (2 x 2 L). The combined organic layers were dried over Na2S04 and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0 to 2% ethyl acetate in hexanes) to afford 4a (215 g, 70% yield) as a viscous colorless liquid. NMR (400 MHz, DMSO-t/6) delta 9.05 (d, J = 1.4 Hz, 1H), 8.98 (dd, J= 1.4, 0.7 Hz, 1H), 4.39 – 4.34 (m, 2H), 1.24 (t, J= 7.1 Hz, 3H).

The synthetic route of 912773-21-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; BOURBEAU, Matthew P.; CHEN, Ning; FROHN, Michael J.; HARRINGTON, Paul E.; LIU, Qingyian; REEVES, Corey; (108 pag.)WO2018/112081; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem