Category: Pyrazines

5049-61-6, 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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

Ethyl bromopyruvate (62.9 g) was added to the DME (258 mL) solution of 2-aminopyrazine (24.8 g) at room temperature and stirred for 2.5 h. The reaction mixture was cooled to 0 C. and stirred for 30 min to afford a pale brown precipitate. The precipitate was filtered and washed with Et2O to give pale brown crystals. The suspension of the precipitate (66.1 g) in EtOH (1.29 L) was heated at reflux temperature to turn to clear solution. After refluxing for 2 h, the reaction mixture was concentrated under reduced pressure, then mixed with CHCl3 and saturated NaHCO3aq. The mixture was filtered through a pad of Celite and the separated organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with CHCl3-MeOH (99/1~97/3), and collected fractions were concentrated under reduced pressure followed by recrystallization from CHCl3-Et2O. The titled compound was obtained as pale pink crystals. Yield: 10.9 g, 22%). 1H NMR(CDCl3)delta d 1.46(t, 3H, J=7.2 Hz), 4.49(q, 2H, J=7.2 Hz), 7.96(d, 1H, J=4.7 Hz), 8.08(dd, 1H, J=1.2, 4.7 Hz), 8.26(s, 1H), 9.21 (d, 1H, J=1.2 Hz).

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; Wyeth; US2006/276445; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, 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. 33332-29-5, name is 2-Amino-5-chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Description 5 2,5-Dichloropyrazine (D5); 5-Chloro-2-pyrazinamine (D4) (753 mg, 5.81 mmol) was dissolved in concentrated hydrochloric acid (8 ml), cooled in an ice-acetone bath and treated with a solution of sodium nitrite (822 mg, 11.9 mmol) in water (6 ml) dropwise over a period of 1 hour. The mixture was transferred to an ice-water bath and left to stir for 1 hour. The mixture was allowed to warm to room temperature over 2 hours, neutralised by addition of an aqueous 50% sodium hydroxide solution and extracted with dichloromethane (x 4). The dichloromethane layers were combined, dried under magnesium sulfate and evaporated. The resulting residue was purified by Biotage column chromatography eluting with 10% ethyl acetate in pentane to afford the title compound (112 mg). ?H NMR (CDCI3) 8.40 (2H, s).

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; GLAXO GROUP LIMITED; WO2005/123723; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

38557-72-1, A common heterocyclic compound, 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, molecular formula is C6H7ClN2, 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.

To a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium (II) acetate (225 mg), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (953 mg) and sodium tert-butoxide (2.7 g) was added toluene (40 mL), and the mixture was refluxed for 8 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 3′,5′-dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g). 3′,5′-Dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL) was added, and the mixture was stirred at room temperature overnight. Ethyl acetate (100 mL) was added, and the mixture was filtered to give the title compound (3.3 g).

The synthetic route of 38557-72-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; EP2364975; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109-08-0, name is 2-Methylpyrazine, 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. 109-08-0

Compound 16: (E)-2-[2-(Pyridin-2-yl)vinyl]pyrazine hydrochloride: s-Butyl lithium (2.5 M in hexanes, 4.8 mL, 12.0 mmol, 1.2 eq.) was added dropwise to a solution of diisopropylamine (1.83 mL, 1.32 g, 13.0 mmol, 1.3 eq.) in dry tetrahydrofuran (25 mL) at -78 ¡ãC. The mixture was stirred at -78 ¡ãC for 10 min and 2-methylpyrazine (0.91 mL, 0.94 g, 10.0 mmol, 1.0 eq.) was added dropwise. The resulting mixture was stirred at -78 ¡ãC for a further 30 min. 2-Pyridinecarboxaldehyde (0.96 mL, 1.07 g, 10.0 mmol, 1.0 eq.) was added dropwise and the mixture was allowed to slowly warm up to room temperature over 1 h while stirring. The reaction was quenched by addition of water (10 mL). The pH was adjusted to -10 by careful addition of cone. HCl and then the mixture was extracted with dichloromethane (2 x 25 mL). The combined organic extracts were washed with brine (25 mL), dried over sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography (Si02, 1:9 methanol-ethyl acetate) to provide 2-(pyrazin-2-yl)-1-(pyridin-2-yl)ethanol (1.08 g, 54percent yield) as a clear yellow oil. p-Toluenesulfonyl chloride (1.12 g, 5.9 mmol, 1.1 eq.) was added to a stirred solution of 2- (pyrazin-2-yl)-1-(pyridin-2-yl)ethanol (1.08 g, 5.4 mmol, 1.0 eq.) and triethylamine (2.24 mL, 1.63 g, 16.1 mmol, 3.0 eq.) in dichloromethane (25 mL). The mixture was stirred at room temperature for 23 h. The mixture was washed with aqueous NaOH (15percent, 25 mL), water (25 mL) and brine (25 mL). The organic layer was dried over sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography (Si02, 1:9 methanol-ethyl acetate) providing a mixture of 2-(pyrazin-2-yl)-1-(pyridin-2-yl)ethyl 4-methylbenzenesulfonate and (E)-2-(2-(pyridin-2-yl)vinyl)pyrazine (0.54 g). l,8-Diazabicyclo[5.4.0]undec-7-ene (0.45 mL, 0.46 g, 3.0 mmol, 2.0 eq.) was added dropwise to a stirred solution of 2-(pyrazin-2-yl)-1-(pyridin-2-yl)ethyl 4-methylbenzenesulfonate (0.54 g, 1.5 mmol, 1.0 eq.) in dichloromethane (10 mL). The mixture was stirred at room temperature for 4 h. The mixture was evaporated in vacuo and the crude product was purified by column chromatography (SiO2, ethyl acetate) providing (E)-2-(2-(pyridin-2-yl)vinyl)pyrazine (0.50 g, 100percent) as a white solid. A solution of hydrochloric acid (2.0 M in diethyl ether, 0.65 mL, 1.3 mmol, 1.2 eq.) was added dropwise to a stirred suspension of (E)-2-(2-(pyridin-2-yl)vinyl)pyrazine (0.20 g, 1.1 mmol, 1.0 eq.) in dry diethyl ether (7.5 mL). The mixture was stirred at room temperature for 1 h and then the solids removed by filtration. The product was washed with diethyl ether (3 x 10 mL) and then dried in vacuo to provide (E)-2-[2-(pyridin-2-yl)vinyl]pyrazine hydrochloride (0.21 g, 83percent yield) as a fine white solid; 1H NMR (400 MHz, DMSO-d6) delta 7.78 (t, J = 7.0 Hz, 1H, Ar), 7.99 (d, J = 16.0 Hz, 1H, C=CH), 8.11 (d, J = 16.0 Hz, 1H, C=CH), 8.25 (d, J = 8.0 Hz, 1H, Ar), 8.38 (t, J = 8.0 Hz, 1H, Ar), 8.65 (d, J = 2.5 Hz, 1H, Ar), 8.75 (t, J = 2.0 Hz, 1H, Ar), 8.79 (d, J = 5.0 Hz, 1H, Ar), 8.88 (d, J = 2.0 Hz, 1H, Ar).

Statistics shows that 109-08-0 is playing an increasingly important role. we look forward to future research findings about 2-Methylpyrazine.

Reference:
Patent; UNIVERSITY COLLEGE DUBLIN – NATIONAL UNIVERSITY OF IRELAND, DUBLIN; THE PROVOST, FELLOWS, FOUNDATION SCHOLARS, AND THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH, NEAR DUBLIN; KENNEDY, Breandan; REYNOLDS, Alison; O’SULLIVAN, Jacintha; BAXTER, Andrew, Douglas; WO2015/107122; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

2423-65-6, These common heterocyclic compound, 2423-65-6, name is Pyrazine 1-oxide, 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.

General Procedure 2:; Palladium-Catalyzed Direct Arylation with Aryl Chlorides and Bromides.; To a dried flask was added the diazine N-oxide (1.0 to 3.0 equiv.), K2CO3 (2.0 equiv.), Pd(OAc)2 (5 mol %) and HP(t-Bu)3BF4 (15 mol %). If the arylhalide is a solid, it is added at this point (1.0 equiv.). The flask and its contents were then purged under nitrogen for 10 minutes. If the aryl halide is a liquid, it is added via syringe after purging, followed by the addition of degassed dioxane (to produce a reaction concentration of 0.3 M relative to the halide). The reaction mixture was then heated at 110 C. until the reaction was complete, after which the volatiles were removed under reduced pressure and the residue was purified via silica gel column chromatography.2-Styrylpyrazine N-oxide (Table 4, Entry 12) Synthesised according to general procedure 2. Purification via silica gel column chromatography using 100% DCM, then a mixture of 10% Acetone/DCM gave a brownish solid, 32% yield with 2 eq. of the N-oxide and 40% yield with 3 eq. of the N-oxide). 1H NMR (300 MHz, CDCl3, 293K, TMS): delta 8.82 (1H, s), 8.31-8.22 (1H, m), 8.14-8.11 (1H, m), 7.72 (1H, d, J=16.5 Hz), 7.62 (2H, dd, J=3.0 and 7.8 Hz), 7.53 (1H, d, J=16.5 Hz), 7.45-7.34 (3H, m) 13C NMR (75 MHz, CDCl3, 293K, TMS): 145.8, 143.9, 136.7, 135.7, 133.9, 129.5, 128.9, 128.4, 127.5, 115.6.

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 2423-65-6.

Reference:
Patent; University of Ottawa; US2008/132698; (2008); 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 138588-41-7 as follows. 138588-41-7

7-chloro-N,N,9-trimethyl-2-pyrazin-2-yl-9H-pyrimido[4,5-b]indole-4-carboxamide 0.6 g (26 mmol) of sodium was dissolved under nitrogen in 150 ml of absolute ethanol. Next, 1.2 g (7.6 mmol) of pyrazine-2-carboxamidine hydrochloride was added. After stirring for 1 h 30 min, the residual insoluble part was isolated by filtration and the filtrate was concentrated under reduced pressure. 150 ml of dichloromethane was added and the mixture was filtered. The filtrate was concentrated under reduced pressure. Added to the residue were 100 ml of xylene, then 0.24 g (0.80 mmol) of 2-(2,6-dichloro-1-methyl-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide, obtained according to step 1.2. from example 1. The mixture was heated under reflux for 18 h. It was then cooled and concentrated under reduced pressure. Dichloromethane, water and a (1M) aqueous solution of sodium hydroxide was added. The organic phase was decanted, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column with a mixture of solvents (dichloromethane/ethyl acetate: 80/20 to 0/100, then ethyl acetate/methanol: 100/0 to 95/5). The compound obtained was recrystallized in an ethyl acetate/methanol mixture, it was isolated by filtration, rinsed with diethyl ether and dried under reduced pressure. 0.070 g of 7-chloro-N,N,9-trimethyl-2-pyrazin-2-yl-9H-pyrimido[4,5-b]indole-4-carboxamide was isolated in the form of a white solid. M.P.: 272-273 C. LC/MS: M+H=367 1H NMR (CDCl3, 200 MHz): 9.9 (s, 1H); 8.9 (d, 1H); 8.7 (d, 1H); 8.1 (d, 1H); 7.6 (d, 1H); 7.4 (dd, 1H); 4.1 (s, 3H); 3.4 (s, 3H); 3.1 (s, 3H).

According to the analysis of related databases, 138588-41-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SANOFI-AVENTIS; US2008/125410; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 33332-31-9, name is 2-Chloro-5-methoxypyrazine, 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 33332-31-9. 33332-31-9

Preparation of tert-butyl 4-((5-methoxypyrazin-2-yl)oxy)piperidine-l- carboxylate. To a solution of tert-butyl 4-hydroxy-4-methylpiperidine-l-carboxylate (278 mg, 1.38 mmol) in DMF (1.7 mL) was added sodium hydride (60% w/w, 61 mg, 1.52 mmol). The reaction was stirred for 5 min at ambient temperature. Then 2-chloro-5-methoxypyrazine (100 mg, 0.692 mmol) was added and reaction stirred overnight at 95C. The reaction was cooled to ambient temperature and diluted with DCM and washed with saturated NaHC03(aq), water, and brine. The combined organic extracts were dried over anhydrous Na2S04(S), filtered and concentrated in vacuo. The residue was purified by silica chromatography (5-40% EtOAc in hexanes as the gradient eluent) to afford the title compound (assumed quantative yield, 214 mg) in sufficient purity for step 2. MS (apci) m/z = 210.1 (M-Boc).

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 2-Chloro-5-methoxypyrazine.

Reference:
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COLLIER, James; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; RAMANN, Ginelle A.; TANG, Tony P.; REN, Li; WALLS, Shane M.; (946 pag.)WO2018/71454; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

87486-34-8, Adding some certain compound to certain chemical reactions, such as: 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, 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 87486-34-8.

A solution of 3,5-dibromo-1-methylpyrazin-2-one (500.0 mg, 2.46 mmol), NH3H2O (5.0 mL) in dioxane (30.0 mL) was heated at 105¡ã C. for 20 h. The mixture was concentrated, diluted with EtOAc (50 mL) and filtrated to give the title compound (300.0 mg, 79.0percent) which was carried on without purification. LCMS (M+H)+ 204.

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 87486-34-8.

Reference:
Patent; Bennett, Michael John; Betancort, Juan Manuel; Boloor, Amogh; Kaldor, Stephen W.; Stafford, Jeffrey Alan; Veal, James Marvin; US2015/111885; (2015); 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. 33332-28-4, name is 2-Amino-6-chloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 33332-28-4

A solution of 82 2-amino-6-chloropyrazine (25 g, 193.1 mmol) in 83 MeOH (500 mL) was treated with 84 NBS (34.3 g, 193.1 mmol), portion-wise, over 1 hour. The resulting mixture was stirred for 16 hours thereafter. TLC analysis at this time shows a small amount of starting material remaining. Another 1.4 g NBS added and reaction heated to 50¡ã C. for 2 hours. The mixture was then cooled to 38¡ã C. and treated with 85 NCS (25.8 g, 193.1 mmol). The reaction mixture was heated to 50¡ã C. for 16 hours thereafter. The mixture was then cooled to room temperature and treated with 39 water (500 mL). The precipitate was collected by filtration and dried in a vacuum desiccator to afford 45.4 g (97percent yield) of 86 2-amino-5-bromo-3,6-dichloropyrazine as a white solid: 13C NMR (75 MHz, CDCl3) ? 149.9 (s), 145.6 (s), 129.6 (s), 121.5 (s). LCMS (15-95percent gradient acetonitrile in 0.1percent TFA over 10 min), single peak retention time=4.51 min on 30 mm column, (M+H)+=244, (M+H+ACN)+=285.

The synthetic route of 33332-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MediBeacon Inc.; Debreczeny, Martin P.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (54 pag.)US2019/125901; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 957344-74-0, name is 5,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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. 957344-74-0

Step 3 4-(5-Bromoimidazo[l,2-a]pyrazin-8-ylamino)-N-(2-diethylaminoethyl) benzene sulfonamide[00262] A mixture of 5,8-dibromoimidazo[l,2-a]pyrazine (1.Og, 3 6mmol), 4-amino-N-(2- diethylaminoethyl)benzenesulfonamide (109mg, 0 4mmol), Pd2(dba)3 (7mg, 0.007mmol), Xantphos(8.4mg, 0.015mmol) and Cs2CO3 (167mg, 0 52mmol) in dioxane is heated at 850C under nitrogen for 18 hours The reaction is cooled to room temperature then evaporated to dryness The residue is chromatographed on silica gel, elutmg with DCM then 98 2 DCM NH3 (7N m MeOH), and the fractions containing the title compound are combined and evaporated to afford a dark oil This oil contains an impurity, but is used in the subsequent step without further purification

The chemical industry reduces the impact on the environment during synthesis 5,8-Dibromoimidazo[1,2-a]pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GALAPAGOS N.V.; WO2007/131991; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem