Category: Pyrazines

57948-41-1, A common compound: 57948-41-1, name is 3-Bromoimidazo[1,2-a]pyrazine, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

3-((Trimethylsilyl)ethynyl)imidazofl,2-aJpyrazine: A mixture of 3 -bromoimidazo[ 1,2-alpyrazine (0.15 g, 0,76 mmol; prepared according to J. Bradac, el al. .1 Org. Chem. (1977), 42,4197 -4201), 0.09 g (0.91 mmol) of ethynyltrimethylsilane, 0.044 g (0.038 mmol) of Pd(PPh3)4,0.014 g (0.076 rnmol) of Cul, and 0.26 mL (1.52 mmol) of diisopropylethylamine in 3.8 mL ofDMF was heated at 50C overnight under an atmosphere of N2. Upon cooling to ambienttemperature, the reaction mixture was concentrated and the crude product was purified by silicagel flash chromatography (eluted with 50% EtOAc/hexanes) to provide 0.15 g of product: 216m/z (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-Bromoimidazo[1,2-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARIAD PHARMACEUTICALS, INC.; GOZGIT, Joseph, M.; RIVERA, Victor, M.; SHAKESPEARE, William, C.; ZHU, Xiaotian; DALGARNO, David, C.; WO2013/162727; (2013); 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. 56423-63-3, name is 2-Bromopyrazine, A new synthetic method of this compound is introduced below., 56423-63-3

To a stirred solution of 2-bromopyrazin (500mg, 3. immol) in dioxan (5mL) were added N({ 2- [(3- { [(tert-butyldimethylsilyl)oxy] methyl }pyridin-2-yl) sulfanyl] -3-chloro-5-(4,4,5 ,5 – tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenyl } methyl)-2-methylpropane-2-sulfinamide (2.3 g, 3.7mmol), Na2CO3 (1.Og ,9.4mmol), water (2mL) and degassed for 10 mm in argon atmosphere. Then to it was added Pd(PPh3)4 (363mg, 0.3 lmmol) and again degassed for 5 mm. The reactionmass was heated to 120C for 16 h. Reaction mixture was then cooled to 25C, filtered through celite pad and washed with EtOAc. The separated organic layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The crude thus obtained was purified by normal silica column using 0-10% methanol in DCM to get N-({2-[(3-{[(tert-butyldimethylsilyl)oxy] methyl }pyridin-2-yl) sulfanyl] -3-chloro-5- (pyrazin-2-yl)phenyl I methyl)2-methylpropane-2-sulfinamide (450mg) as off white solid. LC-MS: 577.1 [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; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ALANINE, Alexander; BEIGNET, Julien; BLEICHER, Konrad; FASCHING, Bernhard; HILPERT, Hans; HU, Taishan; MACDONALD, Dwight; JACKSON, Stephen; KOLCZEWSKI, Sabine; KROLL, Carsten; SCHAEUBLIN, Adrian; SHEN, Hong; STOLL, Theodor; THOMAS, Helmut; WAHHAB, Amal; ZAMPALONI, Claudia; (623 pag.)WO2017/72062; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

56423-63-3, Adding a certain compound to certain chemical reactions, such as: 56423-63-3, name is 2-Bromopyrazine, 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 56423-63-3.

To a solution of Compound 18 (40 mg) in DMF (1.0 ml), NaH (5.2 mg, >55% in minerai oil) was added and after stirring for 30 minutes, 2-bromopyrazine (23.8 mg) was added and the mixture was stirred at room temperature for 0.5 hour. [0220] To the reaction mixture, DMSO (1.0 ml) was added and after filtering off the insoluble matter, the filtrate was purified by reverse-phase preparative HPLC to give the titled compound (6.7 mg, colorless oil.) 1H NMR (600MHz, CHLOROFORM-d) delta 8.34 – 8.29 (m, 1 H), 8.24 – 8.18 (m, 1 H), 8.13 – 8.08 (m, 1 H), 6.28 [6.19] (s, 1 H), 5.60 – 5.36 (m, 3 H), 4.24 – 4.13 (m, 1 H), 3.95 – 3.87 (m, 1 H), 3.82 – 3.69 (m, 1 H), 2.35 – 0.76 (m, 22 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, 2-Bromopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Taisho Pharmaceutical Co., Ltd.; ONO, Naoya; KURODA, Shoichi; SHIRASAKI, Yoshihisa; TAKAYAMA, Tetsuo; SEKIGUCHI, Yoshinori; USHIYAMA, Fumihito; OKA, Yusuke; EP2687524; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19847-12-2, 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. 19847-12-2 name is Pyrazinecarbonitrile, 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.

Example 3 :f4aS RJaS)-7a-f2-fluoro-5-f2-fpyrazin-2-yl)-lH-imidazol-5-vDphenvn-5-methYl- 4a. .7.7a -t etrah ydro-4 H – f tiro Gamma3 ,4-d] f 1.3]thiazin-2-amineStep 1 : 2-(lH midazol-2-yl)py 2,2-Diethoxyethanamine (3 g, 2.25 mmol) was dissolved in dry methanol (20 mL). To this was added sodium methoxide (1.22 g, 22.5 mmol, as a 25% solution in methanol). After stirring for 25 minutes at room temperature,, pyrazine-2-carbonitrile (2.37 g, 22.5 mmol) and acetic acid (1.35 g, 22.5 mmol) were added and the subsequent solution was stirred at 50C for 1 hour. MeOH (40 mL) and 6N HC1 (12 mL) were added and the reaction was stirred at reflux overnight. The reaction mixture was cooled to room temperature and partitioned between 1 : 1 Et20 and water (60 mL) and the layers were separated. The aqueous layer was basified to pH 9/10 and extracted with 10% MeOH in DCM. The combined organic extracts were dried (MgSOa), filtered and concentrated to give the desired compound ( 1.49 g yellow solid). 1 H NMR (400 MHz, eOH-d,) delta ppm: 7.67 (s, 1 H), 7.09 (d, J=1.8 Hz, 1 H), 6.99 (d, J=2.5 Hz, 1 H), 5.72 (s, 2 H)

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

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD; DIMOPOULOS, Paschalis; HALL, Adrian; KITA, Yoichi; MADIN, Andrew; SHUKER, Nicola Louise; WO2012/93148; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

41110-33-2, 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 41110-33-2 as follows.

A solution of lithium aluminium hydride (164.0 mL, 0.164 mol, 1.0 M in THF, 0.5 equiv.) was added to a suspension of methyl 5-methylpyrazine-2-carboxylate (50 g, 0.328 mol, 1.0 equiv.) in anhydrous THF (750 mL) at -78 C (the internal temperature was kept below -72 C during addition of the lithium aluminium hydride). Upon completion of addition, the reaction mixture was stirred at -78 C for a further 20 mm and then quenched with glacial AcOH (50.0 mL) at the same temperature. The resulting mixture was warmed to RT and the volatiles were removed by evaporation under pressure. The residue was dissolved in 1.5 N HC1 (500 mL) and extracted with DCM (2 x 2 L). The organic layers were combined, washed with saturated aqueous NaHCO3 solution (2 x 500 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to yield the initial product as a brown oil. The residue was purified by column chromatography (silica gel 60-120 mesh) eluting with a gradient of 10% EtOAc in petroleum ether to provide the title compound as a pale yellow liquid (21.3 g, 53 %). 1H NMR (400 MHz, CDC13) oe 10.14 (s, 1H), 9.07 (d, J= 1.5 Hz, 1H), 8.63 (d, J= 1.4 Hz, 1H), 2.70 (s, 3H). LCMS (ESI positive ion) m/z:123 (M+H)t

According to the analysis of related databases, Methyl 5-methylpyrazine-2-carboxylate, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; BROWN, Matthew; CHEN, Ning; CHEN, Xiaoqi; CHEN, Yinhong; CHENG, Alan C.; CONNORS, Richard V.; DEIGNAN, Jeffrey; DRANSFIELD, Paul John; DU, Xiaohui; FU, Zice; HARVEY, James S.; HEATH, Julie Anne; HEUMANN, Lars V.; HOUZE, Jonathan; KAYSER, Frank; KHAKOO, Aarif Yusuf; KOPECKY, David J.; LAI, Su-Jen; MA, Zhihua; MEDINA, Julio C.; MIHALIC, Jeffrey T.; OLSON, Steven H.; PATTAROPONG, Vatee; SWAMINATH, Gayathri; WANG, Xiaodong; WANSKA, Malgorzata; YEH, Wen-Chen; (815 pag.)WO2018/97944; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 21948-70-9, name is 2-Methylthiopyrazine, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 21948-70-9

To a mixture of 2-(methylthio)pyrazine (59 mg, 0.46 mmol) and CuI (44.5 mg,0.23 mmol), MeCN (5 mL) was added and the suspension was stirred at ambient temperature for 1 h. The precipitated redorangepowder was centrifuged and re-crystallized from acetonitrile to give 36 mg (35%) of 1. FT-IR (KBr, cm-1): 376 (w),397 (w), 413 (w), 434 (w), 484 (m), 633 (w), 648 (w), 723 (m), 762 (vs), 964 (m), 1007 (m), 1053 (m), 1094 (m), 1130 (m),1159 (s), 1263 (m), 1375 (m), 1420 (s), 1456 (s), 1560 (m), 1584 (s), 2922 (w), 2963 (w), 2982 (w), 3061 (w), 3098 (w).Anal. Calcd (%) for C20H24Cu2I2N8S4: 27.1, 2.7, N 12.6, S 14.5. Found: 27.0, 2.9, N 12.5, S 14.7.

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, 21948-70-9, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Artem?ev; Beresin; Bagryanskaya, I. Yu.; Journal of Structural Chemistry; vol. 60; 6; (2019); p. 967 – 971; Zh. Strukt. Kim.; vol. 60; 6; (2019); p. 1008 – 1012,5;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 313339-92-3 name is 3,5-Dichloropyrazine-2-carbonitrile, 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. 313339-92-3

3,5-dichloropyrazine-2-carbonitrile (500 mg, 2.9 mmol), tert-butyl (R)-2-methylpiperazine-1-carboxylate (460 mg, 2.3 mmol), and K2CO3 (794 mg, 5.75 mmol) were combined in a 40 mLpressure vial. DMF (28 mL) was added and the reaction mixture was allowed to stir at rtovernight. The reaction mixture was then diluted with 3:1 chloroform/IPA (isopropyl alcohol)and washed with saturated, aqueous NH4Cl. The combined organic layers were washed withbrine, dried over magnesium sulfate (MgSO4), and concentrated in vacuo while loading ontosilica gel. The residue was purified by column chromatography (silica gel, eluting with agradient of 0-50% 3:1 EtOAc/EtOH in hexanes to afford tert-butyl (R)-4-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperazine-1-carboxylate (I-1, 1.11 g, 3.29 mmol, 114 % yield), which needed to be dried further on the genevac to afford a pale yellow solid. MS (ESI) Calc?dfor (C15H21ClN5O2) [M+H]+, 338; found, 338.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dichloropyrazine-2-carbonitrile, and friends who are interested can also refer to it.

Reference:
Article; Achab, Abdelghani; Augustin, Martin A.; Bass, Alan; Chen, Dapeng; Christopher, Matthew; Fradera, Xavier; Goldenblatt, Peter; Katz, Jason D.; Lampe, John; Lesburg, Charles A.; Li, Chaomin; Lipford, Kathryn; McGowan, Meredeth A.; Methot, Joey L.; Schroeder, Gottfried; Shaffer, Lynsey; Shah, Sanjiv; Witter, David; Zeng, Haoyu; Zhou, Hua; Bioorganic and medicinal chemistry letters; vol. 30; 1; (2020);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109-08-0,Some common heterocyclic compound, 109-08-0, name is 2-Methylpyrazine, molecular formula is C5H6N2, 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 5 N-((3RS)-1-tert-Butylcarbonylmethyl-2,3-dihydro-2-oxo-5-(2-pyrazinyl)-1H-1,4-benzodiazepin-3-yl)-N’-(3-methylphenyl)urea (Compound 17) STR16 5A Phenacyl pyrazine Phenacyl pyrazine was prepared from methyl pyrazine and methyl benzoate as described by Behun and Levine (J Am Chem Soc 1959, 81, 5157) in 68% isolated yield (chromatography on silica-eluant 60% EtOAc in hexanes).

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

Reference:
Patent; Ferring-Research Limited; Yamanouchi Pharmaceutical Co. Ltd.; US5728829; (1998); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

50866-30-3, Name is 5-Methylpyrazine-2-carbaldehyde, 50866-30-3, belongs to Pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows.

The compound (82.2 mg) obtained in Example 47-3 was dissolved in methanol (5.0 ml) and added with the compound (35.9 mg) obtained in Example 73-1, followed by the addition of sodium cyanoborohydride (36.9 mg). Then, the reaction solution was adjusted to about pH 5 with acetic acid, followed by stirring at room temperature for 16 hours. The reaction solution was added with a saturated aqueous sodium bicarbonate solution and then extracted with chloroform. The organic layer was washed with saturated saline solution and then dried with anhydrous sodium sulfate. Subsequently, the solvent was distilled off. The resulting crude product was purified through silica gel column chromatography (chloroform/methanol) and treated with hydrochloric acid, thereby obtaining hydrochloride (84.0 mg) of the subject compound as a pale-yellow solid. MS(FAB,Pos.):m/z=526[M+H]+1H-NMR(500MHz,DMSO-d6):delta=0.87(6H,t,J=7.3Hz),1.69-1.78(4H,m),2.47(3H,s),2.86-2.95(4H,m),3.82(2H,s),3.85(2H,s),4.11(2H,s),4.26(2H,d,J=5.2H z),7.58-7.62(6H,m),7.88-7.89(2H,d,J=8.7Hz),7.95-7.96(2H,d,J=8.4Hz),8.47(1H,dd,J=0.6,1.3Hz),8.69(1H,d,J=1.4Hz ),10.47(1H,s),10.70(1H,brs),14.51(1H,brs).

Statistics shows that 5-Methylpyrazine-2-carbaldehyde is playing an increasingly important role. we look forward to future research findings about 50866-30-3.

Reference:
Patent; Kureha Chemical Industry Co., Ltd.; EP1550657; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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 dry-ice / acetone cooled solution of scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), was added n-BuLi (2.5 M, 14.1 mL, 0.035 mol) dropwise for 30 mm. After addition, the reaction was stirred at this temperature for 30 mm, followed by dropwise addition of a solution of scheme 5-8 compound S4 (13.6 g, 0.04 mol) in THF (20 mL). The reaction mixture was stirred at this temperature for another 30 mm and allowed to stir at room temperature for 16 h. Then the reaction was quenched with aq. NH4C1 (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10:1) to give the title compound (6 g, yield 50.4%) and scheme 5-8 compound S4 (4.8 g) was recovered.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason Allan; PHADKE, Avinash S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (358 pag.)WO2017/35411; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem