Pyrazines

Electric Literature of 330786-09-9, 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. 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of methyl 3,5-dichloropyrazine-2-carboxylate (100 mg, 0.483 mmol) in dioxane (1.93 mL) were added tert-butyl (4-methylpiperidin-4-yl)carbamate (109 mg, 0.507 mmol) and TEA (0.141 mL, 1.01 mmol) and the resulting mixture was stirred at 24 C for 18 h. H20 (20 mL) was added, and the layers were separated. The aqueous phase was extracted with EtOAc (3 x 20 mL), the combined organic layers were washed with sat NaCl, dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0 – 100 % EtOAc in hexanes) to give the title compound (120 mg, 64%) as pale yellow solid. MS (ES+) C17H25CIN4O4 requires: 384, found: 407 [M+Na]+. ‘H NMR (500 MHz, Chloroform-c d 7.88 (s, 1H), 4.40 (s, 1H), 3.96 (s, 3H), 3.71 – 3.57 (m, 2H), 3.46 – 3.27 (m, 2H), 2.19 – 2.04 (m, 2H), 1.74 – 1.62 (m, 2H), 1.54 – 1.34 (m, 12H). Also isolated regioisomer methyl 5-(4-((tert-butoxycarbonyl)amino)-4-methylpiperidin-l-yl)-3- chloropyrazine-2-carboxylate (60 mg, 32%) as a pale yellow solid. 1 H NMR (500 MHz, Chloroform-c ) d 8.03 (s, 1H), 4.41 (s, 1H), 4.06 – 3.96 (m, 2H), 3.95 (s, 3H), 3.53 – 3.39 (m, (0708) 2H), 2.26 – 2.12 (m, 2H), 1.72 – 1.57 (m, 2H), 1.50 – 1.37 (m, 12H).

The chemical industry reduces the impact on the environment during synthesis Methyl 3,5-dichloropyrazine-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM; JONES, Philip; CROSS, Jason; BURKE, Jason; MCAFOOS, Timothy; KANG, Zhijun; (154 pag.)WO2019/213318; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 17231-50-4,Some common heterocyclic compound, 17231-50-4, name is 3-Amino-6-chloro-2-pyrazinecarbonitrile, molecular formula is C5H3ClN4, 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 solution of 19a (3 g, 20 mmol) in DCM (50 mL) at 0 C was successively added TiCl4(2.2 mL, 20 mmol) and tert-butyl nitrite (7.4 mL, 62 mmol). The reaction mixture was stirred at room temperature for 3 h. When the reaction was completed monitored by TLC, the solvent was evaporated and the residue was treated with water (50 mL) and then extracted with ethyl acetate (2 × 50 mL). The extract was dried over Na2SO4,and concentrated to give 8 as a white solid (2.8 g, yield 81%). 3,6-Dichloropyrazine-2-carbonitrile (8) Yield: 81%, white solid, M.p.: 93-94 C (Lit. 90-91 C,Li 2017). 1H NMR (400 MHz, CDCl3): delta 8.60 (s, 1H). 13CNMR (125 MHz, CDCl3):delta 149.82, 147.65, 147.03, 128.90,112.60. EI-MS m/z: 173 (M+, Cl35,Cl35,100), 175 (M+, Cl35,Cl37,65), 177 (M+, Cl37,Cl37,10).

The synthetic route of 17231-50-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guo, Qi; Xu, Mingshuo; Guo, Shuang; Zhu, Fuqiang; Xie, Yuanchao; Shen, Jingshan; Chemical Papers; vol. 73; 5; (2019); p. 1043 – 1051;,
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Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 19745-07-4, name is 2,5-Dichloropyrazine, 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 19745-07-4, Quality Control of 2,5-Dichloropyrazine

A solution of 2,5-dichloropyrazine (217 mg, 1.46 mmol), tert-butyl ((3S,4S)-3- hydroxypiperidin-4-yl)carbamate (300 mg, 1.387 mmol) and K2CO3 (575 mg, 2.25 mmol) in DMSO (2.3 mL) was stirred at 90 °C for 12 h, then at room temperature overnight. The reaction was diluted with water (15 mL) and extracted with DCM (3 x 15 mL). The combined organic extracts was washed with brine (15 mL), dried over anhydrous Na2S04(S), filtered, and concentrated in vacuo. The crude was purified by silica chromatography (0-15percent MeOH/DCM) followed by reverse phase chromatography (0 to 98percent MeCN/water). The fractions containing product were combined, concentrated to remove most ACN, diluted with sat. NaHCCb (15 mL) and extracted with DCM (3 x 15 mL). The combined organic extracts was washed with brine (15 mL) and dried over anhydrous Na2S04(S), filtered, and concentrated in vacuo to afford the title compound (180.7 mg, 40percent yield). MS (apci) m/z = 329.2 (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, 2,5-Dichloropyrazine, other downstream synthetic routes, hurry up and to see.

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

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. 19847-12-2, name is Pyrazinecarbonitrile belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 19847-12-2

To 20 mL of methyl alcohol is added sodium (109 mg, 4.74 mmol) with stirring. After disappearance of the solid, 2-pyrazinecarbonitrile (5.0 g, 47.6 mmol) is added. The mixture is stirred at room temperature for 6 h, and ammonium chloride (2.8 g, 52.3 mmol) is added. The mixture is then stirred at room temperature for 18 h. Diethyl ether (50 mL) is added to the reaction mixture, and the precipitates are collected by filtration. The solid was washed with diethyl ether (×2) and dried in vacuum oven to give 2-pyrazinecarboxamidine hydrochloride as a white solid (6.5 g). MS: m/z 123.1 (M+H).

The synthetic route of 19847-12-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wyeth; US2005/75357; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 126069-70-3, 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. 126069-70-3, name is 2-(Trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of 800 mg (4.18 mmol) of 2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[l,2-ojpyrazine, 3.36 g of sulfur, and 4 mL of pyridine was stirred at reflux for 3 days and then concentratedto dryness. The residue was triturated with some chloroform to remove impurity and then purified byflash chromatography on silica gel (98:2:0.2 dichloromethane:methanol:concentrated ammoniumhydroxide followed by 97:3:0.3 dichloromethane:methanol:concentrated ammonium hydroxide) to givethe title compound as a yellow-orange solid. LC-MS 222 (M+l).

The chemical industry reduces the impact on the environment during synthesis 2-(Trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK & CO., INC.; WO2006/23750; (2006); A2;,
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 5900-13-0 as follows. Product Details of 5900-13-0

EXAMPLE 49 Sodium hydride (oil free; 0.053 g) was added to a solution of 2-amino-5-bromo-3-methoxypyrazine (0.151 g) in DME (5 ml). The solution was stirred for 10 minutes and then a solution of 4′-methyl-2-biphenylsulphonyl chloride (0.198 g) in DME (2 ml) was added. The solution was allowed to stand for 1 hour and then water (25 ml) was added. 2M Hydrochloric acid (2 ml) was added and the mixture was extracted eith ethyl acetate (2*25 ml). The extracts were washed with water (25 ml) and saturated sodium chloride solution (25ml) and dried (MgSO4). Volatile material was removed by evaporation and the residue was recrystallized from ethyl acetate to give N-(5-bromo-3-methoxy-2-pyrazinyl)-4′-methyl-2-biphenylsulphonamide (0.12 g) m.p. 204-206 C.; 1 H NMR (d6 -DMSO): 2.4 (s,3H), 3.85(s,3H), 7.05-7.2(m,4H), 7.3(dd,1H), 7.55-7.7(m,2H), 7.8(s,1H), 8.1(dd,1H); mass spectrum (+ve FAB, methanol/NBA): 436 (M+H)+.

According to the analysis of related databases, 5900-13-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Zeneca Limited; US5861401; (1999); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5900-13-0, 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. 5900-13-0 name is 5-Bromo-3-methoxypyrazin-2-amine, 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-Bromo-3-methoxy-pyrazin-2-ylamine (A) (816 mg, 4 mmol) and phenyl boronic acid (732 mg , 6 mmol) in toluene (5 mL), ethanol (5 mL) and Na2CO3 (8 mmol, 1 M aqueous) was purged with nitrogen for 10 minutes, and was added PdCl2(PPh3)2 (140 mg, 0.2 mmol). The reaction mixture was stirred at 85 0C for 4 hours. The reaction mixture was cooled to room temperature and diluted with EtOAc (50 mL). The solution was washed with brine (2 X 5 mL). The organic extracts was dried with MgSO4, then solvent was removed under vacuum. The residue was purified with flash column to give product B (660 mg, 82%) as yellow solid. 1H NMR (400 MHz, CDCl3): delta 8.08 (IH, s), 7.92 (2H, d), 7.46 (3H, m), 4.94 (2H, bs), 4.12 (3H, s); MS: 202 (M + H+).

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

Reference:
Patent; NOVARTIS AG; WO2008/73305; (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 51171-02-9 as follows. Formula: C6H5BrN2O2

Step 2: synthesis of N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-oxo-6,7-dihydrothieno[2,3-b]pyrazine-6-carboxamide (100)[0306]A solution of 3-(2-cyanopropan-2-yl)-N-(3-(2-mercaptoacetamido)-4-methylphenyl)benzamide 16 (0.054 mmol, 20 mg), methyl 3-bromopyrazine-2-carboxylate 101 (0.054 mmol, 11.8 mg) and Na2CO3 (1.2 eq, 7 mg) in ethanol (1 mL) was stirred overnight at 70 C. The reaction mixture was quenched in cold 1N HCl solution and extracted with CH2Cl2. Organic layer was dried and evaporated. Purification by chromatography (0-10% methanol in CH2Cl2) gave N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-oxo-6,7-dihydrothieno[2,3-b]pyrazine-6-carboxamide 102 (11 mg, 42.9%). NMR (400 MHz, DMSO-d6) 1.77 (s, 6H), 2.35 (s, 3H), 7.15 (d, J=8.6 Hz, 1H), 7.48 (dd, J=8.2 Hz and 2.3 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.07 (t, J=2.0 Hz, 1H), 8.54 (br s, 1H), 8.62 (br s, 1H), 8.66 (d, J=1.6 Hz, 1H), 10.29 (s, 1H). (m/z)=473 (M+H)+.

According to the analysis of related databases, 51171-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Folmer, Brigitte Johanna Bernita; Man, de Adrianus Petrus Antonius; Gernette, Elisabeth Sophia; Corte Real Goncalves Azevedo, Rita; Ibrahim, Hemen; US2013/79341; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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. HPLC of Formula: C6H6N2O2

5-Methylpyrazin-2-carboxylic acid (13.81 g, 0.1 mol), tert-butanol (95 mL, 1 mol), triethylamine (27.9 mL, 0.2 mol) and diphenylphosphoryl azide (30.27 g, 0.11 mol) were mixed in 300 mL toluene, heated to reflux and reacted for 8 hours, and chromatographed on a silica gel column (petroleum ether – petroleum ether:ethyl acetate=20:1) to obtain a light yellow solid 15.2 g, at a yield of 72.7%.

The synthetic route of 5-Methylpyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KBP Biosciences Co., Ltd.; ZHANG, Yan; ZHANG, Min; LO, HoYin; (52 pag.)EP2781508; (2014); 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. 28643-16-5, name is Methyl 3-amino-5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: Methyl 3-amino-5-chloropyrazine-2-carboxylate

a) 3-Amino-5-vinyl-pyrazine-2-carboxylic acid methyl ester To a mixture of 3-amino-5-chloro-pyrazine-2-carboxylic acid methyl ester (GB 1248146, 161 mg 0.86 mmol), tributyl(vinyl)tin (0.352 ml, 1.204 mmol) and lithium chloride (102 mg, 2.498 mmol) in DMF (4 ml) was added PdCI2(PPh3)2 (30.2 mg, 0.043 mmol) and the mixture was heated to 85 C for 2.5 h. After cooling to room temperature water was added and the mixture was extracted with EtOAc, the combined organic layers were washed with water and half saturated aq. NaCI, dried with Na2S04 and evaporated. The residue was purified by chromatography on silica gel (cyclohexane to cyclohexane/EtOAc 1 :9) to provide the title compound as yellow solid. HPLC: RtH4= 0.71 min; ESIMS [M+H]+ = 179.9; 1H-NMR (600 MHz, DMSO-c 6): delta 8.04 (s, 1 H), 7.35 (br. s, 1 H), 6.75 (dd, 1 H), 6.38 (d, 1 H), 5.70 (d, 1 H), 3.84 (s, 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; NOVARTIS AG; LUEOEND, Rainer Martin; MACHAUER, Rainer; RUEEGER, Heinrich; VEENSTRA, Siem Jacob; WO2013/27188; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem