Month: July 2021

Electric Literature of 875781-43-4, These common heterocyclic compound, 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, 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-Bromo-5H-pyrrolo[3,2-b]pyrazine(4; 0.471 g,2.39 mmol), 4-pyridylboronic acid (0.58 g, 4.72 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloromethane adduct (0.097 g, 0.12 mmol), acetonitrile(3 mL) and 1M sodium carbonate (3 mL) were placed in a 10 mL CEM microwavevial. The vial was capped and irradiated in a CEM microwave reactor for 30minutes at 150 C.Water (3 mL) and ethyl acetate (9 mL) were added the layers were partitioned. Theaqueous layer was extracted with ethyl acetate (2 x 10 mL). The combined organicextracts were washed with saturated sodium chloride (5 mL), dried over MgSO4and concentrated under reduced pressure. The residue was purified by preparativereverse phase HPLC to give 2-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine(14; 0.28 g,60%) as an off white solid: 1H NMR (400 MHz, DMSO-d6) delta 12.24 (s, 1H), 9.00(s, 1H), 8.69 (dd, J = 4.5, 1.6 Hz, 2H), 8.12 (dd, J = 4.5, 1.6Hz, 2H), 7.98 (d, J = 3.6 Hz, 1H), 6.74 (d, J = 3.6 Hz, 1H); ESMSm/z 197.1 (M+1).

Statistics shows that 2-Bromo-5H-pyrrolo[2,3-b]pyrazine is playing an increasingly important role. we look forward to future research findings about 875781-43-4.

Reference:
Article; Burdick, Daniel J.; Wang, Shumei; Heise, Christopher; Pan, Borlan; Drummond, Jake; Yin, Jianping; Goeser, Lauren; Magnuson, Steven; Blaney, Jeff; Moffat, John; Wang, Weiru; Chen, Huifen; Bioorganic and Medicinal Chemistry Letters; vol. 25; 21; (2015); p. 4728 – 4732;,
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. 71257-38-0, name is 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., name: 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine

EXAMPLE 6 2-Benzoyl-1,2,3,4-Tetrahydropyrrolo-[1,2-a]-Pyrazine To a solution of 12.2 g of 1,2,3,4-tetrahydropyrrolo-[1,2-a]-pyrazine and 22.2 g of triethylamine in 50 ml of anhydrous benzene, 15.4 g of benzoyl chloride was added in small portions at 10-15 C. The reaction mass was stirred for 3 hours at room temperature and then poured into water. The organic phase was separated, and washed with a 5% solution of sodium carbonate and then water. The solvent was removed by distillation, the residue was distilled under vacuum, and the fraction with a boiling point of 189-191 C. at 1 mm Hg was collected. The yield of the title compound was 15 g (66.5%). Nmr (CDCl3): delta3.7-3.9 (m) (4H, 3,4-CH2); 4.58 (s) (2H, 1-CH2); 5.6-5.8 (m) (1H, 7-H); 5.8-6.0 (m) (1H, 8-H); 6.2-6.4 (m) (1H, 6 -H); 7.2-7.4 (m) (5H-C6 H5). Anal. calculated for C14 H14 N2 O: C 74.31%; H 6.24%; N 12.38% and found: C 74.21%; H 6.24%; N 12.45%.

According to the analysis of related databases, 71257-38-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Russian-American Institute For New Drug Development; US5378846; (1995); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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 5521-55-1, Recommanded Product: 5-Methylpyrazine-2-carboxylic acid

General procedure: Pyrazine-2-carboxylicacid/ 3-aminopyrazine – 2-carboxylic acid/ 5-methylpyrazine-2-carboxylic acid (0.014mol, 2gm) (compound 1) was reacted with hydrazine hydrate (99%, 0.179 mol)using microwave irradiation (350W)in a microwave oven for 12-15 min. The resulting hydrazide was cooled overnightin a deep freezer. It was further lyophilized to obtain a dry solid product whichwas purified using ethanol.

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-Methylpyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Chitre; Asgaonkar; Miniyar; Dharme; Arkile; Yeware; Sarkar; Khedkar; Jha; Bioorganic and Medicinal Chemistry Letters; vol. 26; 9; (2016); p. 2224 – 2228;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 77112-53-9, 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. 77112-53-9 name is Imidazo[1,2-a]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.

Step 5: Imidazo[l,2-alpha]pyrazine-2-carboxylic acid [2-(4-{4-[(5S)-(acetylamino-methyl)-2- oxo-oxazolidin-3-yl]-2,6-difluoro-phenyl}-piperazin-l-yl)-2-oxo-ethyl]-amide; To a solution of compound (300 mg, 0.57 mmol) obtained in step 4, in DMF (10 mL), were added imidazo[l,2-alpha]pyrazine-2-carboxylic acid (107 mg, 0.66 mmol), EDC (127 mg, 0.66 mmol), HOBt (89 mg, 0.66 mmol) and NMM (0.15 mL, 1.35 mmol) at 0 0C. The reaction mixture was stirred at r.t. and progress of the reaction was monitored by TLC. On completion, DMF was evaporated in vacuo and residue was dissolved in chloroform (100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried over anhydrous sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 1 :20 methanolxhloroform) to provide title compound (220 mg, 69%) as white solid.1H NMR (400 MHz, CDCl3, delta): 2.03 (s, 3H), 3.10-3.25 (m, 4H), 3.50-3.65 (m, 3H), 3.65- 3.75 (m, 2H), 3.80-3.90 (m, 2H), 4.00 (t, J = 9.0 Hz, IH), 4.34 (d, J = 4.5 Hz, 2H), 4.70- 4.85 (m, IH), 5.97 (t, J = 6.1 Hz, IH), 7.12 (d, J = 10.9 Hz, 2H), 7.94 (d, J = 4.7 Hz, IH), 8.09 (dd, J = 4.6 and 1.5 Hz, IH), 8.22 (d, J = 0.5 Hz, IH), 8.35 (t, J = 4.4 Hz, IH), 9.13 (d, J= 0.9 Hz, IH).ESIMS (m/z): 579.3 (M+23), 557.3 (M+l)

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

Reference:
Patent; PANACEA BIOTEC LTD.; JAIN, Rajesh; TREHAN, Sanjay; DAS, Jagattaran; KANWAR, Sandeep; MAGADI, Sitaram, Kumar; SHARMA, Sudhir, Kumar; WO2010/58423; (2010); A2;,
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. 22047-25-2, name is Acetylpyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 22047-25-2

Preparation 4; 1-Pyrazin-2-yl-ethylamine; The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.

The synthetic route of 22047-25-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Roche Palo Alto LLC; US2009/163499; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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.

(Step 6-ii) To a solution of methyl 3-amino-6-bromopyrazine-2-carboxylate (1 g, 4.33 mmol) in 10 mL THF was added a solution of LiOH (540 mg, 12.86 mmol) in 20 mL of water. The mixture was stirred at room temperature for 4 hours and acidified with 6M HCl to a pH of 2. The yellow precipitate was collected by filtration and washed with water. After drying in vacuo, the product, 3-amino-6-bromopyrazine-2-carboxylic acid (600 mg, 2.75 mmol, 64% yield), can be used directly in the next reaction without further purification.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/36272; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 14508-49-7, These common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, 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 solution of 4-allyl-1-(5-(7-bromo-2-(3-ethylureido) benzothiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylate (0.45 g, 0.78 mmol) in DMSO (5.0 mL) was added bis(neopentylglycolato)diboron (0.35 g, 1.57 mmol) and potassium acetate (0.11 g, 1.17 mmol) and the mixture degassed by purging N2 for 15 min followed by addition of dichloro(1,1-bis(diphenylphosphino)ferrocene)palladium (II) (0.057 g, 0.078 mmol). The reaction mixture was again degassed for 10-15 min then heated up to 80 C. for 2 h. After reaction completion the mixture was cooled to rt followed by the addition of 2-chloropyrazine (0.20 g, 1.17 mmol) and aqueous solution of Cs2CO3 (0.38 g, 1.17 mmol, dissolved in minimum amount of water) and the mixture degassed by purging N2 for 15 min followed by addition of tetrakis(triphenylphosphine)palladium (0) (0.09 g, 0.078 mmol). The reaction mixture was again degassed for 10-15 min then heated up to 80 C. for 16 h. After reaction completion, the mixture was poured into 100 mL of ice-cold water, extracted with EtOAc (3×150 mL) and the combined organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The crude residue was purified over 100-200 M silica-gel using 1.50% MeOH: DCM to obtain the desired product as a beige solid (0.26 g, 58% yield). 1H NMR (DMSO-d6): delta 1.09 (t, J=7.20 Hz, 3H), 1.21 (t, J=6.80 Hz, 3H), 1.47 (m, 2H), 2.05 (m, 2H), 2.29 (m, 2H), 3.18 (m, 2H), 3.21 (q, J=7.20, 2H), 4.17 (q, J=6.80 Hz, 2H), 4.46 (m, 2H), 5.05 (m, 2H), 5.72 (m, 1H) 6.80 (br s, 1H), 8.04 (s, 1H), 8.40 (s, 1H); 8.69 (s, 1H), 8.87 (s, 1H), 8.94 (s, 2H), 9.77 (s, 1H) and 10.64 (br s, 1H).

Statistics shows that 2-Chloropyrazine is playing an increasingly important role. we look forward to future research findings about 14508-49-7.

Reference:
Patent; BIOTA EUROPE LTD.; US2012/88750; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.

b) 2,5-Dihydro-3,6-dimethoxy-2-isopropyl-5-(2′-iodo-4′-methoxybenzyl)- (2R,5S)-pyrazine (21); The diastereomeric product 21 was obtained by a reaction of the lithium salt of the chiral auxiliary (2R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine with the bromo derivative 20 using a crucial modification of a procedure reported in the literature [U. Schollkopf, “Enantioselective Synthesis of Non-Proteinogenic Amino Acids via Metallated Bis-Lactim Ethers of 2,5-Diketopiperazines.” Tetrahedron, 39, pp 2085- 2091 (1983)]. Briefly, (2R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (4.39 mL, 24.5 mmol) was dissolved in 4 mL of THF (freshly distilled from LiAlH4). The light yellow solution was cooled to -78° C (dry ice/acetone bath) and stirred for 15 min under argon. A 2.5 M solution of n-butyl lithium (9.79 mL, 24.5 mmol) was added drop wise over a period of 10 min and the mixture was stirred for 20 min at – 78° C. In a separate flask CuCN (1.096 g, 12.23 mmol) was stirred with 4 mL of freshly distilled THF at room temperature for 10 min. The white suspension was then cooled to 0° C (ice bath) and stirred at that temperature for 20 min. The n-BuLi reaction mixture was then transferred to the white suspension of CuCN/THF under argon using a cannula. The resulting yellow suspension turned into a yellow solution within two minutes. The reaction mixture was then stirred at 0° C for 15 min and cooled to -78° C. After 15 min of stirring at -78° C, a solution of bromomethyl anisole derivative 20 (4.00 g, 12.23 mmol) in 6 mL of freshly distilled THF was added drop wise. The color of the reaction mixture changed to greenish brown. After stirring for a further period of 2 hours at -78° C, the reaction mixture was warmed gradually to room temperature. The reaction mixture was then poured into a saturated solution of NH4Cl and extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to provide an oily compound which was purified by flash column chromatography to yield pure 2,5-Dihydro-3,6-dimethoxy-2- isopropyl-5-(2-iodo-4-methoxybenzyl)-(2R,5S)-pyrazine (21) as a yellow oil (3.95 g,percent).1H NMR (CDCl3): delta 7.34 (d, IH, H-31), 7.1 (d, IH, H-61), 6.80 (dd, IH, H-51), 4.25 (dd, IH, H-5), 3.75 (s, 3H, 4′-OMe), 3.73 (s, 3H, 6-0Me), 3.70 (d, IH, H-2), 3.60 (s, 3H, 3-OCH3), 3.60, 2.95 (dd, 2H, CH2), 2.20 (m, IH, CH of isopropyl), 1.00 ( d, 3H, CH3), 0.60 ( d, 3H, CH3). 13C NMR (CDCl3): delta 163.72 (C-3), 163.10 (C-6), 158.23 (C-41), 133.22 (C-I’), 130.84(C-61), 124.23 (C-31), 114.00 (C-51), 101.50 (C-21), 60.47 (C-2), 56.30 (C-5), 55.38 (41-OCH3), 52.54 (6-OCH3), 52.39 (3-OMe), 43.63 (CH2), 31.40 (CH of isopropyl), 19.06(CH3), 16.55 (CH3).MS (ESI) Calcd for CnH23IN2O3 (M+): 430.08; Found: 431.07 (M++l).Figure 15 shows the C-13/H-1 HMBC NMR spectrum of compound 21.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; SATYAMURTHY, Nagichettiar; BARRIO, Jorge, R.; WO2010/8522; (2010); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 36070-80-1, The chemical industry reduces the impact on the environment during synthesis 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

A solution of (R)-tert-butyl 2-methylpiperazine-l-carboxylate (0.5 g, 2.5 mmol), 5-chloropyrazine-2- carboxylic acid (0.4 g, 2.5 mmol), HATU (1.14 g, 3 mmol) and triethylamine (0.64 g, 6.4 mmol) in dichloromethane (5 ml) was stirred at room temperature for 2 hours. To the mixture was added water (30 mL) and the organics were extracted with dichloromethane (20 mL). The organic layer was dried over Na2S04 and concentrated to dryness, and the residue was purified by silica gel flash column chromatography, eluting with ethyl acetate: petroleum ether = 1:5 to afford the title compound (780 mg, 2.29 mmol, 92 % yield). LCMS Method D RT= 1.54 min, ES+ve 241 [M-Boc+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-Chloropyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); 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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine

Compound 49B (2.0 g, 13.0 mmol), platinum dioxide (1 g) and palladium on carbon (0.4 g) were added to methanol (100 mL).Hydrogenation at 50 psi for 14 hours, filtration,The organic solvent is dried under reduced pressure,Compound 49C was obtained as a brown solid product(1.4 g, yield 88%).

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 68774-77-6.

Reference:
Patent; Jiangsu Xiansheng Pharmaceutical Co., Ltd.; Chen Huanming; Liang Bo; Zhao Zhongqiang; Cao Wenjie; Xu Wanmei; Li Qingsong; Wang Jianghuai; Zhang Peng; Jiang Zhaojian; Zhang Guiping; Gao Chunhua; Gong Hongju; Zuo Gaolei; (86 pag.)CN108250128; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem