Author: Jessica.F

Application of 71257-38-0, 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. 71257-38-0 name is 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine, 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.

To a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (4.68 mmol) and 1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazine (3.9 mmol) in methanol (15 ml) there was added, under nitrogen, at 25 C., a catalytic amount of acetic acid, followed by sodium cyanoborohydride (2.5 eq.). The resulting solution was stirred for 16 h at that temperature until the reaction was complete (TLC monitoring). Ice was added to the reaction mixture, and then concentration in vacuo was carried out. The residue was taken up in dichloromethane (100 ml) and washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution. The organic phase was dried (Na2SO4), filtered, and concentrated in vacuo. The crude product so obtained was used directly in the following synthesis step. Yield: 40%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Gruenenthal GmbH; US2008/153843; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 63286-28-2,Some common heterocyclic compound, 63286-28-2, name is 2-Chloro-3-hydrazinylpyrazine, molecular formula is C4H5ClN4, 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.

(2) To a 100 mL eggplant flask were added the above slightly red oil of (S)-2-methylpiperidine-1-carbonylchloride (0.53 g), diisopropylethylamine (1.57 mL), and dichloromethane (20 mL), 2-chloro-3-hydrazinylpyrazine (0.44 g) was added thereto under argon gas flow with stirring at room temperature, and the resulting mixture was stirred at the same temperature for 24 hours. After the reaction was completed, water was added thereto, and the resulting mixture was extracted with dichloromethane. The resulting organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residues were subjected to Moritex medium pressure preparative (Purif-Pack, SI size 20 (10 g), hexane:ethyl acetate=70:30 to 0:100), the fractions comprising the title compound were collected, concentrated under reduced pressure, ethyl acetate and diisopropyl ethyl ether were added thereto, the precipitated solid was collected by filtration, and washed with diisopropyl ethyl ether to give the title compound (23.7 mg) (yield 2.9%) as a colorless solid. MS(DUIS) m/z: 270/272 [M+H]+

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-3-hydrazinylpyrazine, its application will become more common.

Reference:
Patent; MITSUBISHI TANABE PHARMA CORPORATION; UBE INDUSTRIES, LTD.; NAKAJIMA, Tatsuo; HAYASHI, Norimitsu; ISHIZAWA, Kouhei; TSUZAKI, Yasunori; IWAMURA, Ryo; TSUBOIKE, Kazunari; US2019/185479; (2019); 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., Product Details of 56423-63-3

To a reaction flask were added compound 28 (100 mg, 0.189 mmol), 2-bromopyrazine (50 mg, 0.27 mmol), Pd(dppf)Cl2 (5 mg, 0.006 mmol) and sodium carbonate (60 mg, 0.558 mmol), 5 mL glycol dimethyl ether and 0.9 mL water were added, bubbled with nitrogen gas for 10 minutes, and the reaction was heated to 100 C in microwave and reacted for half an hour. After TLC detected the reaction was complete, the reaction was concentrated, purified by silica gel column chromatography to afford 41 mg of a product, yield: 45.3%. LC-MS(APCI): m/z = 480.3 (M+1)+. 1H NMR (400 MHz, CDCl3) delta 8.68 (s, 2H), 8.58 (s, 1H), 8.52 (s, 1H), 8.30 (s, 1H), 8.03 (s, 1H), 7.68 (d, J = 8.9 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 4.91 (d, J = 50.6 Hz, 1H), 4.35 (s, 1H), 3.68 (dd, J = 36.4, 23.2 Hz, 2H), 3.37 – 3.28 (m, 1H), 3.15 (d, J = 12.4 Hz, 1H).

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; Shenzhen Targetrx, Inc.; WANG, Yihan; ZHAO, Jiuyang; AL, Yixin; (55 pag.)EP3553056; (2019); 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. 36070-75-4, name is 5-Chloropyrazine-2-carbonitrile, A new synthetic method of this compound is introduced below., Safety of 5-Chloropyrazine-2-carbonitrile

The 5-chloropyrazine-2-carbonitrile (0.034 mL, 0.368 mmol), rac- I -((2S,3R,4R)-4-amino-2- cyclopropyl-6-(3,6-dihyd ro-2H-pyran-4-yl)-3-methyl-3,4-dihyd roquinolin- I (2H)-yl)ethanone (for a preparation see Intermediate 78, 60 mg, 0.184 mmol), DIPEA (0.096 mL, 0.551 mmol) and Nmethyl-2-pyrrolidone (NMP) (2 mL) were irradiated in a microwave at 200 C for I h. The reactionwas purified directly using a MDAP (Formic) to give a brown solid. This solid was eluted through a NH2 SPE (5 g) using MeOH, the eluent was concentrated and dried to give the product (34 mg, 0.079 mmol, 43.1%) as a brown solid. LCMS (2 mm Formic): Rt = 0.98 mi [MH] = 430.

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; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AMANS, Dominique; ATKINSON, Stephen John; HARRISON, Lee Andrew; HIRST, David Jonathan; LAW, Robert Peter; LINDON, Matthew; PRESTON, Alexander; SEAL, Jonathan Thomas; WELLAWAY, Christopher Roland; WO2014/140076; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 43029-19-2,Some common heterocyclic compound, 43029-19-2, name is 3-Aminopyrazin-2(1H)-one, molecular formula is C4H5N3O, 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 3-aminopyrazin-2-ol (209.35 mg, 1.88 mmol, 1 eq) in DMF (5 mL) was added NaH (82.90 mg, 2.07 mmol, 60% purity, 1.1 eq) at 0C,then the reaction was stirred at 0C for 15 mins then a solution of tert-butyl 5-fluoro-2- (methylsulfonyloxymethyl)indole-1-carboxylate (647 mg, 1.88 mmol, 1 eq) in DMF(10 mL) was dropwised into it , the reaction was stirred at 20C for 12 hr. The reaction was diluted with water (50 mL).The mixture was extracted with ethyl acetate (50 mL*2). The organic phase was washed with brine (50 mL*2) ,dried over anhydrous Na2SO4, filtered and concentrated in vacuum to give a residue. The residue was purified by columnchromatography to give tert-butyl 2-[(3-amino-2-oxo-pyrazin-1-yl)methyl]-5-fluoro-indole-1- carboxylate (I-341) (350 mg, 52% yield) as a yellow solid.1H NMR (400 MHz, CDCl3) d 1.67 (s, 9 H) 5.42 (s, 2 H) 5.48 ( s, 2 H) 6.25 (s, 1 H) 6.58 (d, J=4.63 Hz, 1 H) 6.83 (d, J=4.63 Hz, 1 H) 7.01 (td, J=9.15, 2.65 Hz, 1 H) 7.11 (dd, J=8.60, 2.43 Hz, 1 H) 8.03 (dd, J=9.04, 4.63 Hz, 1 H).

The synthetic route of 43029-19-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SITARI PHARMA, INC.; CAMPBELL, David; CHAPMAN, Justin; CHEUNG, Mui, H.; DIRAIMONDO, Thoams, R.; DURON, Sergio, G.; (615 pag.)WO2020/33784; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4774-10-1,Some common heterocyclic compound, 4774-10-1, name is 3-Methoxypyrazin-2-amine, molecular formula is C5H7N3O, 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 procedure similar to Example 59 (Method B), Parts A and B was used, except that 3-(methyloxy)-2-pyrazinamine (52.4 mg, 0.419 mmol) was used instead of 4-pyrimidinamine to add to the reaction mixture in Part A, to provide the Title compound. MS (ES+) m/z 420.8 (MH+). 1H NMR (400 MHz, METHANOL-d4) delta ppm 1.04-1.21 (m, 2H) 1.36-1.63 (m, 5H) 1.70-1.91 (m, 4H) 2.30-2.44 (m, 1H) 2.44-2.55 (m, 1H) 2.82-2.98 (m, 1H) 3.20-3.29 (m, 1H) 3.51 (dd, J=14.02, 4.42 Hz, 1H) 3.59-3.86 (m, 1H) 3.96 (td, J=9.47, 4.80 Hz, 1H) 4.03 (s, 3H) 4.79-4.87 (m, 1H) 7.79-7.94 (m, 2.7H) 8.26 (s, 0.3H)

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

Reference:
Patent; Glaxosmithkline LLC; Aubart, Kelly M.; Benowitz, Andrew B.; Fang, Yuhong; Hoffman, James; Karpinski, Joseph M.; Knox, Andrew Nicholson; Liao, Xiangmin; Qin, Donghui; Shi, Dongchuan; Spletstoser, Jared T.; US2013/345120; (2013); A1;; ; Patent; GlaxoSmithKline Intellectual Property (No. 2) Limited; Aubart, Kelly M.; Benowitz, Andrew B.; Fang, Yuhong; Hoffman, James; Karpinski, Joseph M.; Knox, Andrew Nicholson; Liao, Xiangmin; Qin, Donghui; Shi, Dongchuan; Spletstoser, Jared T.; US8901119; (2014); B2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 356783-26-1, 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. 356783-26-1, name is Methyl 3,6-difluoropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

EXAMPLE II-2 In 3.0 mL of N,N-dimethylformamide was dissolved 0.3 g of methyl 3,6-difluoro-2-pyrazinecarboxylate. After adding 0.16 g of sodium acetate at an ice-cooled temperature, the mixture thus obtained was stirred at 50 C. for 2.5 hours. The reaction mixture was poured into a mixture of 50 mL of ethyl acetate and 30 mL of water, and the organic layer was separated. The remaining aqueous phase was extracted with three 25 mL portions of ethyl acetate. The organic layers were united, washed successively with 15 mL of water and 15 ml of saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography [eluent: n-hexane:ethyl acetate=1:2] to obtain 0.03 g of methyl 6-fluoro-3-oxo-3,4-dihydro-2-pyrazinecarboxylate as a colorless solid product.

The chemical industry reduces the impact on the environment during synthesis Methyl 3,6-difluoropyrazine-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Toyama Chemical Co., Ltd.; US2003/130213; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 6,8-Dibromoimidazo[1,2-a]pyrazine

Example 23A 6-({2-[(6-Bromoimidazo[1,2-a]pyrazin-8-yl)amino]ethyl}amino)pyridine-3-carbonitrile 8 g (28.9 mmol) of 6,8-dibromoimidazo[1,2-a]pyrazine were dissolved in 80 ml of DMSO, and 16.1 ml (115.6 mmol) of triethylamine and 5.154 g (31.78 mmol) of 6-[(2-aminoethyl)amino]pyridine-3-carbonitrile (Example 2A) were added. The mixture was heated at 140 C. in a microwave for 1.5 h. The solution was poured into water and the precipitate was filtered off. Washing with water and drying under high vacuum gave 10.3 g (94% of theory) of the product as a solid. LCMS (method 8): Rt=0.97 min. (m/z=358 (M+H)+). 1H-NMR (400 MHz, DMSO-d6): delta=8.39 (s, 1H), 8.08 (s, br, 1H), 8.03 (s, 1H), 7.83 (s, 1H), 7.73 (m, 2H), 7.51 (s, 1H), 6.56 (s, br, 1H), 3.5-3.65 (m, 4H).

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 63744-22-9.

Reference:
Patent; BAYER SCHERING PHARMA AKTIENGESELLSCHAFT; US2011/53929; (2011); 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 13134-38-8 as follows. Computed Properties of C6H9N3

b. 2-(Chloromethyl)-5,8-dimethylimidazo[1,2-a]pyrazine To a solution of 3,6-dimethylpyrazin-2-amine (1.0 g, 8.1 mmol) in EtOH (20 mL) was added 1,3-dichloropropan-2-one (1.03 g, 8.1 mmol). The reaction mixture was stirred at reflux for 1 h. Then the solvent was removed. The product was purified by reverse column chromatography to give the title compound as a brown solid (570 mg, yield 85%). ESI MS: m/z 196 [M+H]+. 1H NMR (400 MHz, DMSO-d5): delta 8.10 (s, 1H), 7.65 (s, 1H), 4.94 (s, 2H), 2.70 (s, 3H), 2.54 (s, 3H).

According to the analysis of related databases, 13134-38-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sunovion Pharmaceuticals Inc.; US2012/178748; (2012); 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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Formula: C6H7N3O2

In fitted with magnetic stirring and reflux condensation tube (with drying tail pipe) 250 ml three-necked bottle are respectively added with a 3 – amino pyrazine -2 – carboxylic acid methyl ester 15.4g (about 0.1 muM), 120 ml of concentrated ammonia water, stirring at room temperature under the condition of 10h, filtering, washing, 60 C drying, be 12.5g yellow solid that 3 – amino pyrazine -2 – formamide. Yield: 90.6

The synthetic route of 16298-03-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Li Zhulai; (15 pag.)CN106699759; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem