Month: July 2021

Adding a certain compound to certain chemical reactions, such as: 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine, 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 69214-33-1, Application In Synthesis of 8-Chloroimidazo[1,2-a]pyrazine

To a mixture of 8.-chIoroirnidazo[12.-a]pyrazinc (500 mg, 3.3 rnrnol) in AcOH (5 mL) was added Br2 (800 mg, 5.0 mmol) at RT. The resulting mixture was stirred at RT for 2 days, then poured into water (20 mL) and extracted with EtOAc (15 mL x 3). The combined organic layer was washed with aqueous sodium bicarbonate solution and brine, dried over MgSO,filtered and concentrated in vacuo. The residue was purified by chromatography on silica (9.?16% EtOAc in petroleum ether) to give the title compound (30() mg) as a yellow solid. LRMSm/z (M+H) 232.2, 234.1 found, 231.2, 234.1 required.

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; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Doug C.; MENG, Na; LUO, Yunfu; (127 pag.)WO2016/101119; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 33332-28-4, 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 33332-28-4 as follows.

6-Pyridin-3-ylpyrazin-2-amine An oven dried resealable Schlenk tube was charged with 6-chloropyrazin-2-amine (0.73 g, 5.71 mmol), 3-pyridineboronic acid (0.91 g, 7.42 mmol), dioxane (50 mL) and a 2M aqueous solution of cesium carbonate (8.5 mL, 17.13 mmol). The Schlenk tube was subjected to three cycles of evacuation-backfilling with argon, and 1 ,1′- bis(diphenylphosphino)ferrocene-palladium(ll) dichloride dichloromethane complex (290mg, 0.35 mmol) was added. After three new cycles of evacuation-backfilling with argon, the Schlenk tube was capped and placed in a 9O0C oil bath. After 16h, the mixture was cooled, partitioned between water and ethyl acetate, the aqueous phase extracted twice with ethyl acetate, the organic layers washed with brine, dried (MgSO4) and evaporated. The residue was purified by silica gel flash chromatography (95:5 dichloromethane/methanol) to give the title compound (845 mg, 86percent) as a solid. delta 1H-NMR (CDCI3): 9.18 (s, 1H), 8.67 (d, 1H), 8.38 (s, 1H), 8.25 (m, 1H), 7.99 (s, 1 H), 7.41 (m, 1 H), 4.77 (s, 2H). ESI/MS (m/e, percent): 172 [(M+1)\ C9H8N4].

According to the analysis of related databases, 33332-28-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ALMIRALL PRODESFARMA, S.A.; WO2007/17096; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 681249-57-0, 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. 681249-57-0 name is 2-(Trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyrazine, 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.

5.119 3-(1-OXO-4-((3-((2-(TRIFLUOROMETHYL)-5,6-DIHYDRO-[1,2,4]TRIAZOLO[1,5-A]PYRAZIN-7(8H)-YL)METHYL) BENZYL)OXY)ISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE To the stirred solution of 3-(4-(3-(bromomethyl)benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (500 mg, 1.13 mmol) in DCM (10 mL) was added 2-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine (238 mg, 1.24 mmol) and DIPEA (0.59 mL, 3.38 mmol). The resulting solution was stirred at 40 C. for 27 hrs. The reaction mixture was added by DCM (30 mL) and brine (20 mL). The mixture was extracted and organic layer was dried by MgSO4 and concentrated. The residue was purified by give a glass like solid. The solid was stirred in EtOAc (5 mL) and stirred in diethyl ether (40 mL) to give 3-(1-oxo-4-((3-((2-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)methyl)benzyl)oxy)isoindolin-2-yl)piperidine-2,6-dione as a white solid (391 mg, 62% yield); HPLC: Waters Symmetry C-18, 3.9*150 mm, 5 mum, 1 mL/min, 240 nm, 50/50, (CH3CN/0.1% H3PO4), 3.25 min (95.7%); mp: 213-215 C.; 1H NMR (DMSO-d6) delta 1.92-2.06 (m, 1H, CHH), 2.34-2.47 (m, 1H, CHH), 2.53-2.64 (m, 1H, CHH), 2.82-3.07 (m, 3H, CHH, CH2), 3.81 (s, 4H, CH2, CH2), 4.17-4.49 (m, 4H, CHH, CHH, CH2), 5.05-5.16 (m, 1H, CHH), 5.27 (s, 2H, CH2), 7.28-7.54 (m, 7H, Ar), 10.97 (s, 1H, NH); 13C NMR (DMSO-d6) delta 22.33, 31.16, 45.09, 46.52, 47.73, 49.14, 51.58, 59.55, 69.55, 115.13, 115.28, 126.72, 128.06, 128.44, 128.59, 129.77, 129.96, 133.30, 136.81, 137.47, 152.82, 153.45, 167.96, 170.95, 172.78; LCMS MH=555; Anal. Calcd for C27H25F3N6O4: C, 58.48; H, 4.54; N, 15.16; Found: C, 58.53; H, 4.21; N, 14.89.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(Trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Man, Hon-Wah; Muller, George W.; Ruchelman, Alexander L.; Khalil, Ehab M.; Chen, Roger Shen-Chu; Zhang, Weihong; US2011/196150; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 98-97-5, 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. 98-97-5, name is Pyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

Figure ID shows a table of products produced by using a catalytic redox system comprising 20 mol % organocatalyst lg and 10 mol % CuI2(NMI)4 in MeCN under dry air (4 A molecular sieves) at 50 C, a variety of amides were constructed from 1.0 equiv of a carboxylic acid, 1.2 equiv of an amine, and 1.5 equiv of triethyl phosphite. For workup and isolation, the MeCN was filtered, and the solids were washed with CH2C12. The solvents were evaporated, and the products were obtained by Si02 chromatography. The entries span 1 and 2 amines, aliphatic and aromatic amines, amino acids and amino alcohols/phenols. The method is compatible with oxidation-prone substrates such as alkenes, boron derivatives, and furans and indoles as well as with electron-deficient heterocycles and benzene derivatives, and it works well for amines with a significant range of piH), chiral amine partners, chiral acid partners, and others. No racemization of stereocenters was observed for those substrates studied. The synthesis of peptide 3a shown in was carried out on a 5 g scale and delivered the product in 91% yield after 24 h at 50 C.

The chemical industry reduces the impact on the environment during synthesis Pyrazine-2-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; EMORY UNIVERSITY; LIEBESKIND, Lanny Steven; GANGIREDDY, Pavan Kumar Reddy; AKONDI, Sri Rama Murthy; (97 pag.)WO2017/70157; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 76537-18-3,Some common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, molecular formula is C4H3BrClN3, 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.

Into a three-neck flask equipped with a reflux pipe were put 2.48 g of 3-bromo-5-chloropyrazin-2-amine, 2.19 g of 5-chloro-2-methoxyphenylboronic acid, 2.26 g of potassium fluoride, and 43 mL of tetrahydrofuran, and the air in the flask was replaced with nitrogen. The mixture in the flask was degassed by being stirred under reduced pressure, and then 0.44 g of tris(dibenzylideneacetone)dipalladium(0) and 4.0 mL of tri-t-butyl phosphine were added thereto. The mixture was reacted by being stirred at 80 C for 42 hours. After a predetermined time elapsed, the obtained mixture was suction-filtered and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography using a developing solvent (toluene: ethyl acetate = 10: 1), whereby 1.00 g of 2,8-bis[3-(dibenzothiophen-4-yl)phenyl]benzofuro[2,3- )]pyrazine, which was a target substance, was obtained in a yield of 31 %. A synthesis scheme of Step 1 is shown in (b-1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Bromo-5-chloropyrazin-2-amine, its application will become more common.

Reference:
Patent; SEMICONDUCTOR ENERGY LABORATORY CO., LTD.; YAMAGUCHI, Tomoya; YOSHIZUMI, Hideko; KIDO, Hiromitsu; TAKAHASHI, Tatsuyoshi; SEO, Satoshi; (162 pag.)WO2018/122664; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 160252-31-3, 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. 160252-31-3 name is 1-(5-Chloropyrazin-2-yl)ethanone, 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.

A mixture of (4-(3-(cyclopropylmethoxy)phenoxy)-2,6-difluorophenyl)methanol (60 mg), 1-(5-chloropyrazin-2-yl)ethanone (33.7 mg), sodium hydride (60% in oil, 11.75 mg) and THF (1 ml) was stirred at room temperature for 10 min, and then stirred under microwave irradiation at 135C for 1 hr. To the mixture was added water at 0C, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by HPLC (acetonitrile/water, addition of 0.1% TFA) to give the title compound (20 mg). 1H NMR (300 MHz, CDCl3) delta 0.31-0.42 (2H, m), 0.61-0.70 (2H, m), 1.22-1.30 (1H, m), 2.66 (3H, s), 3.79 (2H, d, J = 7.0 Hz), 5.47 (2H, s), 6.53-6.68 (4H, m), 6.76 (1H, ddd, J = 8.3, 2.4, 0.8 Hz), 7.27-7.34 (1H, m), 8.18-8.23 (1H, m), 8.81-8.88 (1H, m).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(5-Chloropyrazin-2-yl)ethanone, and friends who are interested can also refer to it.

Reference:
Patent; Takeda Pharmaceutical Company Limited; MIZOJIRI, Ryo; ASANO, Moriteru; TOMITA, Daisuke; BANNO, Hiroshi; TAWADA, Michiko; NII, Noriyuki; GIPSON, Krista E.; MAEZAKI, Hironobu; TSUCHIYA, Shuntaro; IMAI, Mayumi; AMANO, Yuichiro; (100 pag.)EP3279183; (2018); A1;,
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 36070-75-4, These common heterocyclic compound, 36070-75-4, name is 5-Chloropyrazine-2-carbonitrile, 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.

A solution of tert-butyl 4-((2S,3R,4R)- I -acetyl-4-amino-2,3-dimethyl- I ,2,3,4-tetrahydroq uinolin-6- yl)piperazine-1-carboxylate (for a preparation see Intermediate 213, 69 mg, 0.151 mmol) in NMP (1.5 mL) was treated with 5-chloropyrazine-2-carbonitrile (22 mg, 0.158 mmol) and DIPEA (0.079mL, 0.453 mmol) then the mixture was heated at 200 C for 30 mm using a microwave reactor. The residue was purified by MDAP (Formic). The desired fractions were combined and evaporated in vacuo to afford the desired product as a white solid (17 mg).LCMS (2 mm Formic): Rt = 0.82 mi [MH] = 407.

The synthetic route of 36070-75-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AMANS, Dominique; ATKINSON, Stephen John; HARRISON, Lee Andrew; HIRST, David Jonathan; LAW, Robert Peter; LINDON, Matthew; PRESTON, Alexander; SEAL, Jonathan Thomas; WELLAWAY, Christopher Roland; WO2014/140076; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 622392-04-5,Some common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, molecular formula is C4H2BrIN2, 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-bromo-5-iodopyrazine (503 mg, 1.77 mmol) and tert-butyl piperazine-1-carboxylate (355 mg, 1.91 mmol) were taken up in tBuOH (8 mL). iPr2NEt (400 muL, 2.3 mmol) was added and the stirred reaction mixture was heated to 100 C. After 66 h, the reaction mixture was cooled and was partitioned between EtOAc, water and brine. The phases were separated, and the organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (10-30% EtOAc in hexanes) to afford tert-butyl 4-(5-iodopyrazin-2-yl)piperazine-1-carboxylate 7.11.

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-iodopyrazine, its application will become more common.

Reference:
Patent; Gilead Scientific Systems, Inc.; Cory, Kevin S; Doo, Jimin; Farrand, Julie; Guerrero, Juan A; Katana, Ashley A; Cato, Daryl; Laisaweed, Scott I; Lee, Jiayao; Lingco, John O; Nicolaus, May; Notte, Gregory; Phyen, Hyeoung-Jung; Sangy, Michael; Sumit, Arun C; Adam J, Surayyah; Stephens, Cork L; Venkatraman, Chandrasekar; Watkins, William J; Yang, Jong Yu; Jabloki, Jeff; Jifel, Shiela; Ro, Jennifer; Lee, Sung H; Jao, Chung Dong; Grove, Jeffery; Su, Jianjun; Blomgren, Peter; Mitchell, Scott A; Shyung, Jin Ming; Chandrasekar, Jayaraman; (460 pag.)KR2016/37198; (2016); A;,
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