Month: March 2021

4858-85-9, name is 2,3-Dichloropyrazine, 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. Application In Synthesis of 2,3-Dichloropyrazine

2,3-Dichloropyrazine (2 mL, 13 mmol) was dissolved in 95% ethanol (4 mL) and to this was added, dropwise and with stirring, hydrazine anhydrous (2 mL, 67 mmol). During the addition of the hydrazine the solution became warm and yellowish. Following cooling of this mixture in an ice bath, the resulting material was isolated by filtration, washed with cold aqueous 95% ethanol to riled 1-(3-chloropyrazin-2-yl)hydrazine (1.42 g, 73% yield) as white crystals. No further purification was done. MS m/z: 145.0 (M+1).

The synthetic route of 4858-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Amgen Inc.; US2010/120774; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 54608-52-5, These common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, 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.

Synthesis of 4-bromo-A, -(pyrazin-2-yl)benzohydrazide (15): 4-Bromohcnzoic acid (0.5 g, 2.4 mmol) was dissolved in dichloromethane (20 mL) and cooled to 0 C. 2- Hydrazinylpyrazine (0.32 g, 2.9 mmol), EDCI (0.55 g, 2.9 mmol), HOBt (0.39 g, 2.9 mmol) and DIPEA (0.96 g, 7.4 mmol) were added at 0 C. The reaction mixture was allowed to warm to room temperature and stirred for 4 h. The reaction mixture was transferred into water (100 mL) and extracted with CH2C12 (3 x 25 mL). The combined organic layers were washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure to give crude product, which was purified by silica gel chromatography (0-5% MeOH in CH2C12) to obtain 4-bromo-N’-(pyrazin-2-yl)benzohydrazide (15). (Yield: 0.15 g, 20%). LCMS: m/z 295. 18 [M+2], = 1.8 min.

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KARYOPHARM THERAPEUTICS INC.; BALOGLU, Erkan; SHACHAM, Sharon; SENAPEDIS, William; MCCAULEY, Dilara; LANDESMAN, Yosef; GOLAN, Gali; KALID, Ori; SHECHTER, Sharon; WO2015/3166; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 3149-28-8, A common heterocyclic compound, 3149-28-8, name is 2-Methoxypyrazine, molecular formula is C5H6N2O, 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.

1) Preparation of 2-Iodo-3-methoxypyrazine To 20 ml of an anhydrous THF solution of 1.3 g of diisopropylamine was added 4.8 ml (2.5 M hexane solution) of n-butyllithium at -78 C., and the mixture was stirred at that temperature for 20 minutes. To the reaction mixture was added 10 ml of a THF solution of 1.1 of 2-methoxypyrazine, followed by stirring at -78 C. for 1 hour. To the reaction mixture was further added 10 ml of a THF solution of 4.0 g of iodine, followed by stirring for 4 hours while gradually elevating the temperature to room temperature. The reaction mixture was diluted with ethyl acetate, washed successively with a saturated sodium thiosulfate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography using chloroform as a developing solution. The fraction containing the desired compound was concentrated to give 0.49 g of the title compound. 1H-NMR (CDCl3) delta: 4.02 (s, 3H), 7.94 (d, 1H, J=2.5 Hz), 7.99 (d, 1H, J=2.5 Hz).

The synthetic route of 3149-28-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Daiichi Pharmaceutical Co., Ltd.; US6169086; (2001); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 19847-12-2, name is Pyrazinecarbonitrile, 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 19847-12-2, Formula: C5H3N3

In order to expand the scope of this flow method, a variety of nitriles were subjected to the optimized conditions in the entry 6 (Table 1), and the results are summarized in Tables 3 and 4 {Method A). For substrates 2 and 3, where no electron- donating or electron- withdrawing group was present on the aromatic ring, or substrate 4 where the nitrile was rendered electron poor by the presence of electron- withdrawing group at the para position, the reactions proceeded to 100% conversions without the formation of any side product. Similarly, meta tolunitrile (5) and the hetero aromatic substrates (6-8) also showed excellent conversions. Electron rich nitriles 10 and 10 reacted to give moderate but clean conversions to the corresponding tetrazoles. The biphenyl nitriles 9, 13 and 14 also proved to be good substrates for this reaction regardless of position of the phenolic hydroxy group on the second aromatic ring.Notably, chiral nitrile 15 provided 15a, a derivative of which (no CBZ group) has found utility as an organocatalyst, in > 99% ee and 92% yield based on conversion. To test if an increase in the ? can drive the reaction of moderately yielding substrates to completion, the model substrate 1 was reacted at a ? of 30 min (Table 4). There was no significant change in the conversion observed; instead a small amount of hydrolysis product la was formed. However, significant improvement in the reaction rate was observed by doubling the concentration of the reaction (0.4 M). For nitrile 1, the conversion increased from 65% to 81% (? = 30 min), while similar improvement in conversions were observed for substrates 11 and 13-15 when the reaction concentration was doubled.As this continuous flow method has the advantage of using high temperatures in a safe manner, it was determined that the presence of a catalyst (e.g., ZnBr2) was not essential for all reactions carried out at these temperatures. To test this, the flow process was repeated with selected substrates without the use of ZnBr2 (Tables 3 and 4, Method B). The non- substituted benzo- and napthonitrile substrates (2 and 3), electron poor nitrile (4), and the heterocyclic substrates (6, 7 and 8), all showed excellent conversions to corresponding tetrazoles in the absence of ZnBr2. The conversions were found to decrease moderately in case of biphenyl substrates 9, 13 and 14 indicating decrease in the reaction rate of these substrates in the absence of ZnBr2. Similar decrease in conversion was observed for the electron rich substrates (1 and 12), but it was noted that there was no side product observed in the absence of ZnBr2 even at 30 min of residence time. This shows that ZnBr2 may be promoting the competing side reaction. Thus, the use of ZnBr2 may be useful for enhancing the conversion of the electron-rich nitriles, but can also lead to formation of side product. In many, if not all instances, reactions without ZnBr2 can give clean conversions. To demonstrate the scale-up capabilities of this, the synthesis of 3a was carried out using aUniqsis FlowSyn continuous flow reactor. FlowSyn is an integrated continuous flow reactor system that uses a pair of high pressure pumps to deliver reagent solutions through a ‘T’-mixer into the electrically heated flow coil or column reactors. The homogenous solution of reagents ([3] = 1M; [NaN3] = 1.05 M) in NMP:H20 (7:3) was pumped using a single pump through a coiled PFA tubing reactor (volume of heated zone ~ 6.9 mL) with a flow rate of 0.35 mL/min (tr = 20 min) at 190 C (see Example 2). The flow process was run continuously for 2.5 h to obtain 9.7 g of 3a in 96 % yield. This corresponds to a product output of 4.85 g/h or 116 g/day for the tetrazole 3a.Overall, the method performed is a safer alternative for currently used methods to synthesize 5-substituted tetrazoles as the hazards due to accumulation and condensation of HN3 are greatly minimized. Only uses a slight excess of NaN3 (1.05 equiv) was used, and hence the production of azide waste is minimal. The method is highly efficient and clean, and works for a wide range of substrates. In case of substrates where the reaction does not go to completion, the remaining NaN3 in the reaction can be quenched by introducing streams of sodium nitrite and sulfuric acid after the reaction is complete. The incorporation of this quenching procedure increases the overall safety of the process. Therefore, given the widespread applications of tetrazoles in chemical andpharmaceutical industry, this method can serve as a safe and highly efficient alternative for synthesis of tetrazoles.EXAMPLE 2This example provides additional experimental details and data in connection with Example 1.General protocol for continuous flow synthesis of tetrazoles (Method A):Sodium azide (68 mg, 1.05 mmol) was added to a solution of zinc bromide (111 mg, 0.5 mmol) in 0.5 mL water. To this solution was added the nitrile substrate (1 mmol) dissolved in 4.5 mL of N-methylpyrrolidone (NMP) and the result…

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; MASSACHUSETTS INSTITUTE OF TECHNOLOGY; JAMISON, Timothy, F.; PALDE, Prakash, B.; WO2012/24495; (2012); 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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, A new synthetic method of this compound is introduced below., Formula: C6H4BrN3

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).

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:
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

Adding a certain compound to certain chemical reactions, such as: 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, 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 63744-22-9, HPLC of Formula: C6H3Br2N3

Step-(iii): Synthesis of (4-((6-bromoimidazo [1, 2-a] pyrazin-8-yl) amino) phenyl)(morpholino) methanone:To a stirred solution of Intermediate-lOb (7.0 g, 19.6 mmol), Intermediate-8b (4.0 g, 19.6 mmol) in 70 mL of DMF was added, DIPEA (10.68 mL, 58.82 mmol) and stirred at 110C for 20h. The reaction mixture was distilled under a reduced pressure to remove the solvent. Theresidue was taken in water and extracted with DCM (2 x 250 mL). The combined organic phases were washed with brine, dried over sodium sulphate and concentrated. The obtained crude product was purified by colunm chromatography using 100-200 mesh silica gel and 5% MeOH in DCM as eluent to give the titled product as a pale brown viscous solid (4.8 g, 61%); 1H NMR (400 MHz, DMSO-d6): oe 10.21 (s, 1H), 8.33 (s, 1H), 8.07 (d, 2H, J=8 Hz), 7.98 (s, 1H), 7.97 (s,1H), 7.43 (d, 2H, J=8.8 Hz), 3.61-3.5 1 (m, 8H); MS (ES) m/z 402 (M+1).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; AURIGENE DISCOVERY TECHNOLOGIES LIMITED; BORUAH, Anima; HOSAHALLI, Subramanya; PANIGRAHI, Sunil Kumar; WO2014/125410; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 24241-18-7, 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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Step 1: Synthesis of Compound (A’) as Described in the General Reaction Scheme; 2-chloro-3,5-dibromo-pyrazineTo a well stirred solution of 2-amino-3,5-dibromopyrazine (3.21 g, 12.692 mmol) in DCM (20 1 mL) cooled to 0 C. is added TiCl4 (2.41 g, 12.692 mmol, 1.00 equiv.) in one portion, thus giving a dark red slurry. t-Butylnitrite (2.62 g, 25.385 mmol, 2.00 equiv.) is then added dropwise, causing the solution to turn bright yellow. The ice bath is then removed and the reaction is then allowed to proceed at room temperature. More TiCl4 (1.50 g, 1.2 equiv.) is added and the mixture is stirred further for one hour. At that point an orange solution has formed and LC-MS shows full conversion of the starting material to the desired product which ionises very poorly. Water (100 1 mL) is added to the reaction, forming an emulsion. DCM (50 1 mL) is added, and the DCM layer is separated, and the aqueous layer is further extracted with DCM (3¡Á50 mL) until the DCM layer is colorless. The DCM layers are gathered, washed with brine and dried over anhydrous Na2SO4, to yield after solvent removal, compound A’ (2.81 g, 82%) as an orange oil, which is used as such in the following step.

The synthetic route of 2-Amino-3,5-dibromopyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Andrews, Martin James Inglis; Chambers, Mark Stuart; Van De Poel, Herve; Bar, Gregory Louis Joseph; US2009/286798; (2009); 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. 33332-28-4, name is 2-Amino-6-chloropyrazine, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H4ClN3

EXAMPLE 1C 6-(3-butenyloxy)-2-pyrazinamine A suspension of NaH (60percent, 618 mg, 15.45 mmol) in dioxane (30 mL) at 0¡ã C. was treated with 3-buten-1-ol (1.33 mL, 15.45 mmol), stirred for 2 hours, treated with 2-amino-6-chloropyrazine (1 g, 7.72 mmol), stirred at 100¡ã C. for 2.5 days, cooled to room temperature, and diluted with ethyl acetate. The mixture was washed with water, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography eluding with hexanes/ethyl acetate (2:1) to provide the desired product (390 mg, 31 percent). MS (DCI/NH3) m/z 166.12 (M+H)+; 1H NMR (500 MHz, benzene-d6) delta 2.66 (m, 2H), 4.42 (t, J=6.87 Hz, 2H), 5.24 (dd, J=10.22, 1.98 Hz, 1H), 5.30 (m, 1H), 6.04 (m, 1H), 7.64 (s, 1H), 7.65 (s, 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; Tao, Zhi-Fu; Lin, Nan-Horng; Wang, Le; Sowin, Thomas J.; US2005/96324; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1458-16-8,Some common heterocyclic compound, 1458-16-8, name is Methyl 3-amino-6-iodopyrazine-2-carboxylate, molecular formula is C6H6IN3O2, 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 dimethylformamide (60 ml) suspension of copper (II) bromide (19.2 g, 86.0 mmol) raised in temperature to 50C, t-butyl nitrite (5.7 ml, 43.0 mmol) was added and subsequently a dimethylformamide (60 ml) suspension of 3-amino-6-iodopyrazine-2-carboxylic acid methyl ester (see Patent Document: WO2006/015124)(12.0 g, 43.0 mmol) was added dropwise and the mixture was stirred for one hour. The reaction mixture was charged with t-butyl nitrite (11.4 ml, 86.0 mmol) and was further stirred for 30 minutes at an external temperature of 50C. The reaction solution was poured into a 3 M aqueous hydrochloride solution (60 ml) of sulfamic acid (7.6 g) under ice cooling and extracted with ethyl acetate, dried (over anhydrous magnesium sulfate), filtered and concentrated to obtain a residue, which was purified by silica gel column chromatography [developing eluent: hexane: ethyl acetate = 5:1 to 1:1]. The resultant low polarity product was washed with hexane-ethyl acetate to obtain 3-bromo-6-iodopyrazine-2-carboxylic acid methyl ester (6.38 g) in the form of a white solid substance. A high-polarity product was washed with ethyl acetate to obtain 3-hydoxy-6-iodopyrazine-2-carboxylic acid methyl ester (2.70 g) in the form of a yellow solid substance. 3-Bromo-6-iodopyrazine-2-carboxylic acid methyl ester MS (ESI): 342 (M+1) 1H NMR (300 MHz, CDC13) delta ppm 4.02 (d, J = 0.55 Hz, 3 H) 8.72 (s, 1 H) 3-Hydoxy-6-iodopyrazirie-2-carboxylic acid methyl ester MS (ESI): (ES+) 281 (ES-) 279 1H NMR (300 MHz, DMSO) delta ppm 3.82 (s, 2.53 H) 3.84 (s, 0.47 H) 8.35 (s, 0.78 H) 8.39 (s, 0.22 H) 12.69 – 13.03 (br, 1 H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-iodopyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; Taisho Pharmaceutical Co. Ltd.; Nissan Chemical Industries, Ltd.; EP2157090; (2010); 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. 5049-61-6, name is Pyrazin-2-amine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of Pyrazin-2-amine

Aminopyrazine (10 g, 10.5 MMOL) was dissolved in dry DIMETHYLFORMAMIDE (60 ml) and was treated with N-CHLOROSUCCINIMIDE (15.36 g, 11.5 MMOL) under argon at 0 C. The mixture was stirred for 30 minutes and then allowed to warm to room temperature. The mixture was poured onto water and extracted with diethyl ether. The diethyl ether layers were combined and evaporated in vacuo. The resulting residue was purified by column chromatography eluting with a mixture of ethyl acetate : pentane (1: 9) to afford the title compound (1.40 g) ;’H NMR (CDC13) 8.02 (1 H, S), 7.76 (1H, s), 4.61 (2H, s).

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; WO2004/56369; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem