Category: 4949-13-7

Synthetic Route of 4949-13-7, The chemical industry reduces the impact on the environment during synthesis 4949-13-7, name is 2-Fluoropyrazine, I believe this compound will play a more active role in future production and life.

General procedure: To a 5 mL vial containing a stir bar, 3-(2-aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenol (80 mg, 0.31 mmol) and 2-chloropyrimidine (41 mg, 0.34 mmol) were added Cs2CO3 (203 mg, 0.62 mmol) and DMSO (0.8 mL). The resultant mixture was stirred at 120 Celsius for approximately 1 hour via microwave irradiation. The reaction mixture was cooled to room temperature before passing the mixture through a syringe filter and subjecting the filtrate to FCC to afford the title compound (81 mg, 78%). The title compound was prepared using conditions similar to those described in Example 160 with DMSO as the solvent, heating for 2 hours at 80 Celsius via microwave radiation and substituting Intermediate B and 2-fluoropyrazine. MS (ESI): mass calcd. for C18H16FN6O, 337.13; m/z found, 337.9 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 8.53 (d, J=1.3 Hz, 1H), 8.49-8.42 (m, 1H), 8.27 (d, J=2.7 Hz, 1H), 8.12-8.03 (m, 2H), 7.85-7.76 (m, 1H), 7.23 (s, 1H), 4.70 (s, 2H), 3.68-3.56 (m, 1H), 2.26-2.08 (m, 4H), 2.03-1.89 (m, 1H), 1.87-1.76 (m, 1H).

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, 2-Fluoropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; Eccles, Wendy; Fitzgerald, Anne E.; Hack, Michael D.; Hawryluk, Natalie A.; Jones, William M.; Keith, John M.; Krawczuk, Paul; Lebsack, Alec D.; Liu, Jing; Mani, Neelakandha S.; McClure, Kelly J.; Meduna, Steven P.; Rosen, Mark D.; US2014/221310; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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.

10264] To a 2.5 M solution of n-butyllithium (40 mE, 0.1 mol) in anhydrous THF (250 mE) cooled to -78 C. under N2 protection was added TMP (2,2,6,6-tetramethylpiperidine, 15 g, 0.106 mol) dropwise over a period of 20 minutes. The mixture was warmed to 0 C. by replacing the dry ice/acetone bath with an ice bath and stirred for 1.5 h. The mixture was cooled back to -78C. and a solution of 9a (3 g, 0.03 mol) and tributyltin chloride (10 g, 0.03 mol) in SOmE of dry THF was added over 10 mm. The mixture was stirred at -78 C. for 6 h, then warmed to -40 C. by replacing the dry ice/acetone bath with an dry ice/acetonitrile bath. A solution of 35% HC1, ethanol and THF (1:4:5) was added. The mixture was warmed to room temperature and washed with saturated NaHCO3 solution (100 mE) and extracted with EtOAc (3×100 mE). The combined organic layers were dried over anhydrous Na2504 and concentrated under reduced pressure. The residue was purified by column chromatography (silica, EtOAc:petroleum ether=1:15) to provide 9b (3.4 g, 29% yield) as light yellow oil. ?H-NMR (CDC13, 300 MHz): oe=8.41 (d, 1H), 8.17 (d, 1H), 1.8-0.53 (m, 27H).

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; Helsinn Healthcare SA; Giuliano, Claudio; Garcia Rubio, Silvina; Daina, Antoine; Guainazzi, Angelo; Pietra, Claudio; US2015/252021; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4949-13-7,Some common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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.

Preparation of intermediate DM A suspension of intermediate G (0.238 g, 1.01 mmol), 2-fluoropyrazine (0.123 mL, 1.52 mmol) and potassium carbonate (420 mg, 3.04 mmol) in DMSO (6.2 mL) was heated at 120 C using a single mode microwave (Biotage initiator60) with a power 25 output ranging from 0 to 400 W for 1 h [fixed hold time]. The reaction mixture was evaporated in Genevac and purified by preparative LC (irregular SiOH, 15-40 muiotaeta, 40 g, Merck, dry loading (silica), mobile phase gradient from DCM/MeOH from 100/0 to 90/10) to give 0.194 g of intermediate DM as a yellow solid (69%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Fluoropyrazine, its application will become more common.

Reference:
Patent; JANSSEN SCIENCES IRELAND UC; GUILLEMONT, Jerome, Emile, Georges; MOTTE, Magali, Madeleine, Simone; RABOISSON, Pierre, Jean-Marie, Bernard; TAHRI, Abdellah; (194 pag.)WO2017/1660; (2017); 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. 4949-13-7, name is 2-Fluoropyrazine, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 4949-13-7

In a dry flask under argon, 2-fluoropyrazine (1.95 g, 19.9 mmol) and cyclopropanecarbonitrile (1.5 mL, 20. mmol) were dissolved in dry toluene (25 mL). The solution was cooled to 0 C and potassium bis(trimethylsilyl)amide (1.0 M in THF, 20 mL, 20 mmol) was added slowly over 5 min via syringe. The black, opaque reaction mixture was allowed to warm to room temperature and stir for 4 h. The reaction was diluted with H2O (200 mL) and EtOAc (200 mL) and the layers were separated. The aqueous layer was back extracted with EtOAc (2x 100 mL). The combined organic layers were dried over Na2S 04, filtered and concentrated to give a black oil. The oil was purified by flash chromatography (silica, 20- »60% EtOAc/hexanes) to give 849 mg of the title compound as a light yellow oil, m/z 146.17 [M+l]+

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 4949-13-7.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG; WO2009/70485; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4949-13-7, 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. 4949-13-7, name is 2-Fluoropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

[0220] To a mixture of (4-bromophenyl)methanamine hydrochloride (2.2 g, 9.9 mmol, (0654) 1.0 equiv) and IPA (15 mL) in a microwave vial (20 mL) were added 2-fluoropyrazine (1.1 g, 10.9 mmol, 1.1 equiv) and DIPEA (3.1 g, 23.7 mmol, 2.4 equiv). ). The vial was sealed and heated at 170 C in a microwave reactor for 4 h. The mixture was concentrated onto 10 g of Si02 and purified by silica gel chromatography (80 g column, 0-10% MeOH in DCM) to provide 1.65 g (63%) of A-(4-bromobenzyl)pyrazin-2-amine as an off-white solid. LRMS (ES) m/z 264.0 (M+H).

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

Reference:
Patent; CYTOKINETICS, INC.; MORGAN, Bradley P.; VANDERWAL, Mark; CHUANG, Chihyuan; (0 pag.)WO2020/5888; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 4949-13-7, 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. 4949-13-7, name is 2-Fluoropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Step A: Ethyl 3(2,4-difluorophenyl)-1-(pyrazin-2-yl)-1H-thieno[2,3-c]pyrazole-5-carboxylate Ethyl 3-(2,4-difluorophenyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate (82.0 mg, 0.266 mmol), 2-fluoropyrazine (134.6 mg, 1.372 mmol) and cesium carbonate (263.7 mg, 0.809 mmol) were dissolved in N,N-dimethylformamide (2.60 mL) at 25 C under Ar. The reaction mixture was heated to 80 C allowed to stir for 2 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (10 mL), and the mixture extracted with ethyl acetate (3 x 15 mL). The combined organic phases were washed with saturated aqueous ammonium chloride (2 x 10 mL) and saturated aqueous sodium chloride (1 x 10 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 40 g column) on a CombiFlash Rf purification system eluting with ethyl acetate-hexanes (0-50%). The title compound (55.3 mg, 0.143 mmol, 53.8 % yield) was recovered as a light yellow/white solid. LC-MS [M+1] = 387.3.

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, 2-Fluoropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Merck Sharp & Dohme Corp.; BURGEY, Christopher, S.; CROWLEY, Brendan, M.; DENG, Zhengwu, J.; PAONE, Daniel, V.; POTTEIGER, Craig, M.; (109 pag.)EP2411001; (2018); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 4949-13-7, name is 2-Fluoropyrazine, 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 4949-13-7, SDS of cas: 4949-13-7

Reagent 142-Fluoro-3-(tributylstannyl)pyrazineA clear solution of 2,2,6,6-tetramethylpiperidine (4.1 ml, 24.29 mmol) in tetrahydrofuran (150 mL) was cooled to -30 C and treated with n-butyl lithium (9.0 ml, 22.50 mmol). The internal temperature (IT) rose from -37 to -26 C. The reaction mixture was stirred at room temperature (IT=15 C) for 0.5 hours and then placed in a N2(1)/MeOH bath and cooled to an internal temperature of -122 C. A solution of 2-fluoropyrazine (2.0889 g, 21.30 mmol) in tetrahydrofuran (50 ml) was added via cannula over 4 minutes (IT=103). After 5 min, the tributyltin chloride (7 ml, 25.81 mmol) was added and the mixture was maintained at -100 C for 1 hr 40 minutes. The dark brown solution was quenched with 1:4:5 35% aqueous HCl:EtOH:THF, allowed to warm to room temperature over 35 minutes, made slightly basic with sodium bicarbonate, concentrated to a residue, and then partitioned between methylene chloride and water. The aqueous layer was extracted with methylene chloride (3×150 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to afford the crude product as a light brown oil which was purified on silica gel using a gradient of 100:0 to 60:40 hexanes:ethyl acetate over 35 minutes to afford the desired product as a clear oil (2.26 g, 27%).

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

Reference:
Patent; ASTRAZENECA AB; US2008/318943; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 4949-13-7, These common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, 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.

2-fluoropiperidine4a (6 mL, 74.20 mmol) and cyclopropyl nitrile (5.74 mL, 77.9 mmol) were dissolved in dry toluene (60 mL).Nitrogen protection, 0 C, Sodium bis(trimethylsilyl)amide (39 mL, 78 mmol) was slowly added, and the reaction was naturally stirred at room temperature for 4 hours. The reaction was quenched by dropwise addition of saturated aqueous ammonium chloride (100 mL), and extracted with ethyl acetate (300 mL×2). The combined organic phase was washed with saturated sodium chloride solution (200 mL×2) Sodium drying, suction filtrationThe residue was purified by silica gel column chromatography (EtOAc/EtOAc (EtOAc)A pale yellow solid 4b (1.34 g, yield 12%) was obtained.

Statistics shows that 2-Fluoropyrazine is playing an increasingly important role. we look forward to future research findings about 4949-13-7.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Li Jianhao; Gu Zheng; Tang Wanjun; Kang Panpan; (43 pag.)CN109721555; (2019); A;,
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. 4949-13-7, name is 2-Fluoropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 4949-13-7

Butyl lithium solution (2.5 M in hexane, 881 mL, 2.01 mol) and 1.5 L of dry THF were charged into a flame-dried 5.0 L round bottomed flask. The flask was cooled to -50 0C and 2,2,6,6-tetramethylpiperidine (312.0 mL, 2.20 mol) was added dropwise . The reaction mixture was warmed to 0 0C without taking the cold bath away and kept at that temperature for 20 min. The reaction was then cooled to -78 0C, and 2-fluoropyrazine (180 g, 1.84 mol) in 150 mL of THF was added dropwise. The mixture was kept at -78 0C for 5 min. Iodine (464 g, 1.84 mol) in 500 mL of THF was added dropwise and the reaction mixture was kept at -78 0C for 1 h. The reaction was quenched with the addition of 250 mL of concentrated HCl, 250 mL MeOH and 250 mL THF at -78 0C. The cold bath was then removed, and aqueous sodium bisulfite was added to get rid of traces of unreacted iodine. The solvent was evaporated and the residue was diluted with water and adjusted to pH 8. The mixture was extracted with ethyl acetate (3 x 1.5 L). Combined ethyl acetate layer was dried over sodium sulfate and concentrated. The crude product was purified by column chromatography (Silica: 100-200 mess, solvent: 10% EtOAc/hexanes) to give the title compound as a white solid.

The synthetic route of 4949-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; BOURBEAU, Matthew P.; CHEN, Ning; HU, Essa; KUNZ, Roxanne; RUMFELT, Shannon; WO2010/57121; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4949-13-7, 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 4949-13-7 as follows.

STEP 1. 2-FLUORO-3-IODOPYRAZINE Butyl lithium solution (2.5 M in hexane, 881 mL, 2.01 mol) and 1.5 L of dry THF were charged into a flame-dried 5.0 L round-bottomed flask. The flask was cooled to -50 C. and 2,2,6,6-tetramethylpiperidine (312.0 mL, 2.20 mol) was added dropwise. The reaction mixture was warmed to 0 C. without taking the cold bath away and kept at that temperature for 20 min. The reaction was then cooled to -78 C., and 2-fluoropyrazine (180 g, 1.84 mol) in 150 mL of THF was added dropwise. The mixture was kept at -78 C. for 5 min. Iodine (464 g, 1.84 mol) in 500 mL of THF was added dropwise and the reaction mixture was kept at -78 C. for 1 h. The reaction was quenched with the addition of 250 mL of concentrated HCl, 250 mL MeOH and 250 mL THF at -78 C. The cold bath was then removed, and aqueous sodium bisulfite was added to get rid of traces of unreacted iodine. The solvent was then evaporated and the residue was diluted with water and adjusted to pH 8. The mixture was extracted with ethyl acetate (3*1.5 L). Combined ethyl acetate layer was dried over sodium sulfate and concentrated. The crude product was purified by column chromatography (Silica:100-200 mess, solvent: 10% EtOAc/hexanes) to give the title compound as a white solid.

According to the analysis of related databases, 4949-13-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; US2010/160280; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem