Month: August 2021

Synthetic Route of 69214-33-1, 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. 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

To the solution of compound 9 (6.47 g, 42.13 mmol) indichloromethane (140 ml) N-bromosuccinimide (7.50 g,42.13 mmol) was added and the mixture was stirred at roomtemperature for 3 h. The reaction mixture was diluted withdichloromethane and stirred with 10% aqueous sodium carbonatesolution for 1 h before the layers were separated. The organic layerwas washed with water (2), dried over sodium sulphate, filteredand concentrated under reduced pressure. The crude product was triturated with diisopropyl ether and filtered to give the titlecompound (14.40 g)

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

Reference:
Article; Garamvoelgyi, Rita; Dobos, Judit; Sipos, Anna; Boros, Sandor; Illyes, Eszter; Baska, Ferenc; Kekesi, Laszlo; Szabadkai, Istvan; Szantai-Kis, Csaba; Keri, Gyoergy; Oerfi, Laszlo; European Journal of Medicinal Chemistry; vol. 108; (2016); p. 623 – 643;,
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. 313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, A new synthetic method of this compound is introduced below., Safety of 3,5-Dichloro-6-ethylpyrazine-2-carboxamide

Weighing compounds 1-3 (165 mg, 0.52 mmol), 1-4 (137 mg, 0.62 mmol) in a reaction flask, After stirring with 1,4-dioxane, N,N-diethylisopropylamine (DIPEA) (201 mg, 1.56 mmol) was added, warmed to 100 C and stirred for 12 h. After stopping the reaction, the reaction solution was cooled to room temperature, a small amount of water was added, the solid was precipitated, suction filtration, and the filter cake was rinsed with ethanol for 2 times and dried. The yellow solid product 1-5, 125 mg was obtained.

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; Chinese Academy Of Sciences Shanghai Pharmaceutical Institute; Zhang Ao; Geng Meiyu; Ye Jiqing; Ai Jing; Song Zilan; (29 pag.)CN109384774; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

13301-04-7, name is Methyl 3,6-dibromopyrazine-2-carboxylate, 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. Product Details of 13301-04-7

To a solution of methyl 3,6-dibromopyrazine-2-carboxylate (8.4 g, 28.3 mmol) in MeCN (142 mL) was added (3Patent; REVOLUTION MEDICINES, INC.; LI, Jie Jack; KOLTUN, Elena S.; GILL, Adrian Liam; BUCKL, Andreas; WON, Walter; AAY, Naing; MELLEM, Kevin; TZITZILONIS, Christos; JOGALEKAR, Ashutosh; CREGG, James Joseph; (177 pag.)WO2019/75265; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1379338-74-5, The chemical industry reduces the impact on the environment during synthesis 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, I believe this compound will play a more active role in future production and life.

(A) methyl 3-(7-chloropyrido[4,3-ib]pyrazi n-5-ylamino)propanoate.[01 62] A solution of methyl 3-aminopropanoate hydrochloride (4.88 mmol), Et3N (6.50 mmol) and 5,7-dichloropyrido[4,3-£>]pyrazine (3.25 mmol) in THF (10 mL) was stirred at room temperature overnight. Volatiles were removed under reduced pressure, and the residue was treated with water and extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered, and concentrated. The residue was purified by chromatography to afford the title compound. MS (m/z): 267 (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, 5,7-Dichloropyrido[3,4-b]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; HUTCHISON MEDIPHARMA LIMITED; SU, Wei-Guo; DENG, Wei; JI, Jianguo; WO2012/167423; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 889447-19-2,Some common heterocyclic compound, 889447-19-2, name is 2-Chloro-5H-pyrrolo[2,3-b]pyrazine, molecular formula is C6H4ClN3, 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 1M solution of iodine chloride in dichloromethane (4ml, 4mmol) was added dropwise to an ice-cold solution of 2-chloro-5H-pyrrolo[2,3-&]pyrazine (4) in N-methylpyrrolidone (residual from previous step) and pyridine (5ml). The reaction mixture was stirred for 60 minutes at O0C and then was concentrated in vacuo. The residue was purified by flash chromatography, using as eluent pentane/EtOAc 0% to 50%, to give the title compound (820 mg, 75% over two steps). 1Eta NMR (DMSO-d6) 8.2 (lEta,s), 8.4 (IH, s). MS(ES+): 280

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-5H-pyrrolo[2,3-b]pyrazine, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2006/58074; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 4858-85-9,Some common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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. Preparation of the intermediate compounds; A1. Preparation of intermediate compound 1; 2,3-Dichloropyrazine (10 g, 62.12 mmol) and 1-(phenylmethyl)-4-piperidinamine (13.73 mL, 67.12 mmol) were dissolved in DMF (60 ml). Then Na2CO3 (10.09 g, 1 14.10 mmol) was added. The reaction was stirred at 130 0C for 16 hours. The solid was filtered off, washed with AcOEt and the solvent was evaporated till dryness. The product was dissolved in AcOEt, washed with H2O and brine, dried with MgSO4 and evaporated under vacuum yielding 15 g of the desired intermediate compound 1 (74 %).The product was used without any further purification.

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

Reference:
Patent; JANSSEN PHARMACEUTICA N.V.; WO2007/122173; (2007); 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. 14667-55-1, name is 2,3,5-Trimethylpyrazine, A new synthetic method of this compound is introduced below., SDS of cas: 14667-55-1

Take 2,3,5-trimethylpyrazine (16.3 mL, 98.7 mmol) in a 500 mL round bottom flask, glacial acetic acid (60 mL) and 30% hydrogen peroxide (50 mL) were slowly added with a constant pressure funnel while stirring in an ice bath, the reaction solution was stirred and heated in an oil bath at 60 C, an equal amount of 30% hydrogen peroxide was added dropwise to the reaction solution, and the mixture was stirred for 20 hours, cooled to room temperature, water (50 mL) was added, rhoEta was adjusted = 9 with saturated K2C03, extracted with DCM (200mLX4), the organic phase was washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated to give 12.4 g of a pale yellow oily liquid, yield was 76%.

The synthetic route of 14667-55-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guizhou Medical University; Fan Lingling; Tang Lei; Li Yi; Li Yong; Liu Jian; Chu Liangzhao; (28 pag.)CN108558833; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 54608-52-5, 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 54608-52-5 as follows.

Step 1 2,2-difluoro-N’-pyrazin-2-yl-acetohydrazide difluoroacetate Pyrazin-2-yl-hydrazine 23a (1 g, 9 mmol) was added in an eggplant-shaped bottle (25 mL), followed by dropwise addition of difluoroacetic anhydride (4 g, 22.98 mmol) at 0 C. After stirring at room temperature for 3 hours, the reaction mixture was concentrated under reduced pressure to obtain crude 2,2-difluoro-N’-pyrazin-2-yl-acetohydrazide difluoroacetate 23b (2 g) as a brown oil. The product was used directly in the next reaction without purification.

According to the analysis of related databases, 54608-52-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JIANGSU HANSOH PHARMACEUTICAL CO., LTD.; Tang, Peng Cho; Li, Xin; Li, Xiangqin; Chen, Yang; Wang, Bin; Zhu, Zhe; US2013/131068; (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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, A new synthetic method of this compound is introduced below., Safety of 2-Bromo-5-chloropyrazine

A mixture of 2-bromo-5-chloro-pyrazine (2 g, 10.34 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2-[(lR)-2,2,2-trifluoro-l- methyl-ethoxy]pyridine (3.12 g, 9.31 mmol), Pd(dppf)Cl2 (1.13 g, 1.55 mmol) and CS2CO3 (6.74 g, 20.68 mmol) in l,4-dioxane (100 mL) and water (10 mL) was stirred under N2 at 50 C for 5 hours. After cooling to room temperature, the mixture was diluted with EtOAc (10 mL), filtered with silica gel, eluted with EtOAc (20 mL) and concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 20%) to give the product (2500 mg, 7.21 mmol, 70% yield) as a solid. ‘H NMR (400MHz, CDCI3) dH= 8.77 (d, 1H), 8.64 (d, 1H), 8.53 (d, 1H), 8.08 (dd, 1H), 6.00 – 5.83 (m, 1H), 1.59 (d, 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; PRAXIS PRECISION MEDICINES, INC.; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; MARTINEZ BOTELLA, Gabriel; REDDY, Kiran; WITTMANN, Marion; (0 pag.)WO2019/232209; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 87486-33-7, name is 3,5-Dichloro-1-methylpyrazin-2(1H)-one, 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. COA of Formula: C5H4Cl2N2O

A solution containing 3,5-dichloro-l-methylpyrazin-2(lH)-one (300 mg, 1.676 mmol) (CAS 87486-33-7), tetramethyltin (0.256 mL, 1.844 mmol) and tetrakis(triphenylphosphine)palladium(0) (48.4 mg, 0.042 mmol) in DMF (2 mL) in a Biotage microwave vial was sealed with a Teflon-lined septa cap. The vial was evacuated under vacuum and backfilled with nitrogen gas, using a needle from a vacuum manifold. The procedure repeated and the nitrogen line removed. The vial was heated in a Biotage microwave at 150 C for 20 min. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (50 mL) and washed with aqueous 10% NaF solution (2×10 mL) and saturated aqueous NaCl solution (1×10 mL), dried (Na2S04), filtered and concentrated. The crude product was dissolved in a small amount of DCM and charged to a 10 g ISCO silica gel column, placed on a Teledyne ISCO system and eluted over a 20 min gradient using 0%-100% hexanes/ethyl acetate eluent to afford 5- chloro-l,3-dimethylpyrazin-2(lH)-one (170 mg, 1.072 mmol, 64.0 % yield). LCMS MH+: 159.0. HPLC Ret. Time 0.52 min. Method Bl. NMR (400 MHz, CHLOROFORM-d) delta 7.13 (bm, 1H), 3.52 (s, 3H), 2.48 (d, J=0.6 Hz, 3H). Fragment 21 : 6-Chloro-2,4,5-trimethylpyridazin-3(2H)-one

The synthetic route of 3,5-Dichloro-1-methylpyrazin-2(1H)-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; DYCKMAN, Alaric J.; DODD, Dharmpal S.; HAQUE, Tasir Shamsul; WHITELEY, Brian K.; GILMORE, John L.; (192 pag.)WO2019/28302; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem