Pyrazines

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

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

21943-17-9,Some common heterocyclic compound, 21943-17-9, name is 5-Bromo-3-chloropyrazin-2(1H)-one, molecular formula is C4H2BrClN2O, 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: A solution of 56 (1.50 g, 7.16 mmol), the appropriate secondary amine (8.59 mmol, 1.20 equiv) and diisopropylethylamine (1.50 mL, 8.59 mmol) in n-butanol (15 mL)was heated in a microwave reactor using variable wattage to 140 C for 1 h. The mixture was concentrated and purified by flash column chromatography on silica, eluting with 9:1 dichloromethane/methanol, to give gave 58-63.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-3-chloropyrazin-2(1H)-one, its application will become more common.

Reference:
Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728,16;; ; Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

870787-06-7, 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. 870787-06-7 name is 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, 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 compound (2 mmol) represented by the formula (2-1) was added to a 100 mL round bottom flask.EDCI (2.4 mmol), HOBt (2.4 mmol) and 10 mL of DMF were reacted at 25 C for 1 h.Then, the compound represented by formula (2-21) or formula (2-22)(2.4 mmol) was added to the above solution,Reaction at 25 C for 24 h,After removing the solvent, column chromatography gave the desired product (yield of the desired product as a one-step yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; Central China Normal University; Yang Guangfu; Li Hua; Xiong Li; (10 pag.)CN109666004; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4774-14-5, 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of diisopropylamine (23.5 mL, 167.7 mmol) in THF (400 mL) at -20 C. was added n-butyllithium (1.6 M solution in hexanes, 104 mL, 166 mmol) dropwise and the reaction mixture was stirred at the same temperature for 30 minutes (min). Then the reaction mixture was cooled to -78 C. and a solution of 2,6-dichloropyrazine (10 g, 67 mmol) in THF (400 mL) was added drop wise over a period of 1.5 hr. The reaction mixture was stirred for additional 1 hr. Then the reaction mixture was poured on to dry ice and allowed to warm to room temperature over a period of 16 hr. The reaction mixture was treated with 1.5 N HCl (200 mL) and extracted with EtOAc. The EtOAc layer was extracted with saturated sodium bicarbonate solution; the aqueous layer was acidified with 1.5 N HCl, extracted with EtOAc, washed with brine and concentrated to obtain the product as pale yellow solid. The solid thus obtained was not purified further and used as such for the next step.Yield: 9 g (69.5%).1H NMR (300 MHz, DMSO-d6): 8.9 (s, 1H)

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sudhakar, Anantha; US2011/105497; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 95-89-6, name is 3-Chloro-2,5-dimethylpyrazine, 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. 95-89-6

In a pressure tube were placed 4 mL of 25% ammonia solution, 64 mg of powdered copper and 1.0 g (6.66 mmol) of 3-chloro-2,5-dimethylpyrazine. The whole was heated to 150 C for 18 hours. Further 1 mL of 25% ammonia solution was added and heating was continued for further 4 hours. The mixture was filtered through silica gel layer, washed with 10 mL of water and 10 mL of ethyl acetate. The filtrate was extracted with ethyl acetate (5 x 10 mL). Organic phase was dried over sodium sulphate and concentrated. Resulted solid was triturated with heptane and filtered-off (first crop). Second crop of the product crystallized from the filtrate. Combined solids were dried under reduced pressure to obtain 0.60 g of 2-amino-3,6-dimethyl- pyrazine as a solid (yield 73%). MR (300 MHz, DMSO-d6): delta 7.45 (s, 1H), 6.01 (s, broad, 2H), 2.22 (s, 3H), 2.10 (s, 3H).

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, 95-89-6, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CELON PHARMA S.A.; MOSZCZYNSKI-PETKOWSKI, Rafal; BOJARSKI, Lukasz; WIECZOREK, Maciej; MAJER, Jakub; JANOWSKA, Sylwia; MATLOKA, Mikolaj; BORKOWSKA, Malgorzata; STEFANIAK, Filip; LAMPARSKA-PRZYBYSZ, Monika; DUBIEL, Krzysztof; WO2015/177688; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, molecular formula is C7H5ClN2, 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. 136927-64-5

To a solution of the crude amine in 0.16 mL of diisopropylethylamine was added 1-chloropyrrolo[1,2-a]pyrazine (0.047 g, 0.31 mmol) followed by 1 drop of 1-butyl-3-methylimidazolium tetrafluorborate. The reaction was heated at 90 C. for 20 h. Purification of the residue by HPLC afforded (S)-6-chloro-N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)quinazoline-2-carboxamide (0.05 g, 0.013 mmol, 6%). 1H NMR (400 MHz, CD3OD) delta 9.60 (s, 1H), 8.26 (s, 1H), 8.17 (d, J=9.1 Hz, 1H), 8.07 (dd, J=1.8, 9.1 Hz, 1H), 7.76 (d, J=1.5 Hz, 1H), 7.72 (d, J=5.8 Hz, 1H), 7.57 (s, 1H), 6.93 (m, 1H), 6.85 (d, J=5.8 Hz, 1H), 5.06-4.84 (m, 1H), 4.82-3.60 (br, 4H), 2.65-2.40 (br, 2H); MS: (ES) m/z calculated for C20H17ClN6O [M+H]+393.2. found 393.

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

Reference:
Patent; ChemoCentryx, Inc.; Fan, Junfa; Krasinski, Antoni; Lange, Christopher W.; Lui, Rebecca M.; McMahon, Jeffrey P.; Powers, Jay P.; Zeng, Yibin; Zhang, Penglie; US2014/154179; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

313340-08-8, A common heterocyclic compound, 313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, molecular formula is C7H7Cl2N3O, 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.

Compound6(10 mmol) was dissolved in 2N HCl/MeOH (15 ml) solution. The mixture was stirred at 70oC for 7 h. The solution was concentrated under vacuum, diluted with saturated NaHCO3(60 ml) and then extracted with CH2Cl2(3¡Á80 ml). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product7aslight yellowsolid in 81% yield.

The synthetic route of 3,5-Dichloro-6-ethylpyrazine-2-carboxamide has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wang, Yueliang; Xing, Li; Ji, Yinchun; Ye, Jiqing; Dai, Yang; Gu, Wangting; Ai, Jing; Song, Zilan; Bioorganic and Medicinal Chemistry Letters; vol. 29; 6; (2019); p. 836 – 838;,
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 4774-14-5 as follows. 4774-14-5

0662] To a solution of fert-butyl azetidin-3-ylcarbamate hydrochloride (LXII) (2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9 mmol). To this mixture was added 2,6-dichloropyrazine (LXIII) (1.428 g, 9.58 mmol) and the reaction was stirred at 95C for 3 h. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous NaaSO/t, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes?hexanes:EtOAc 1 : 1) to yield fert-butyl (l-(6- chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXIV) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C12H17CIN4O2 mlz 285.1 (M+H).

According to the analysis of related databases, 4774-14-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; MARAKOVITS, Joseph Timothy; BOLLU, Venkataiah; HOOD, John; (293 pag.)WO2017/23988; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

117719-17-2, The chemical industry reduces the impact on the environment during synthesis 117719-17-2, name is 5-Bromo-3-morpholinopyrazin-2-amine, I believe this compound will play a more active role in future production and life.

To a solution of Intermediate 1-02 (3 g, 9.288 mmol) in 2-propanol (46 mL), 2- chloro-3-oxo-succinic acid diethyl ester (6.2 g, 27.865 mmol) was added. The reaction mixture was heated in a Parr reaction vessel at 90 C for 2 days. The solvent was evaporated and the residue was purified by automated column chromatography (Biotage, EtOAc:Cyclohexane, 0: 100 to 40:60). The product obtained was treated with Et20 and filtered to give the expected product 1-39 (1.2 g, 34 %) as a white solid.

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

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONC&Oacgr;LOGICAS (CNIO); PASTOR FERNANDEZ, Joaquin; MARTINEZ GONZALEZ, Sonia; ALVAREZ ESCOBAR, Rosa Maria; RODRIGUEZ ARISTEGUI, Sonsoles; GONZALES CANTALAPIEDRA, Esther; HERNANDEZ HIGUERAS, Ana Isabel; VARELA BUSTO, Carmen; WO2011/36461; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem