Category: Pyrazines

19745-07-4, 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 19745-07-4 as follows.

A mixture of A-63 (10.00 g, 67.12 mmol) in EtOH (80 mL) was stirred under N2 at 80 C for 16 hours. The mixture was concentrated to give the crude product, which was triturated from H20 (20 mL) to give A-64 (1.60 g, 11.07 mmol) as a solid. 1H NMR (400MHz, CDCI3) _ = 8.10 – 8.01 (m, 2H), 6.03 (br s, 1H), 3.85 (br s, 2H).

According to the analysis of related databases, 2,5-Dichloropyrazine, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; REDDY, Kiran; MARTINEZ BOTELLA, Gabriel; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; (364 pag.)WO2018/98499; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, molecular formula is C6H4BrN3, 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. 875781-43-4

Step 1: 2-Bromo-5H-pyrrolo[2,3-b]pyrazine (1.98 g, 10.0 mmol) was dissolved in DMF (33 mL) and cooled down to 0 C. NaH (60%, 0.480 g, 12.0 mmol) was added slowly. After the addition was complete stirring was continued for 30 minutes at 0 C. (2-Chloromethoxy-ethyl)-trimethyl-silane (2.1 mL, 12.0 mmol) was added and the reaction mixture was allowed to warm up overnight. The reaction was quenched with H2O. The aqueous layer was extracted with EtOAc. The organic layer was dried (MgSO4), filtered, concentrated, and purified by SiO2 chromatography (150 g SiO2, hexanes/EtOAc 0-35% EtOAc) to give 2.81 g of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine as a yellow liquid (86% yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 875781-43-4, its application will become more common.

Reference:
Patent; Bamberg, Joe Timothy; Hermann, Johannes Cornellius; Lemoine, Remy; Soth, Michael; US2010/144745; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

356783-16-9, name is 3,6-Dichloropyrazine-2-carbonitrile, 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. 356783-16-9

A mixture of 8 (2.6 g, 15.0 mmol), KF (5.23 g, 90.0 mmol), tetrabutylammonium bromide (1.93 g, 6.0 mmol) was predried under vacuum over phosphorus pentoxide. The mixture was charged in a polytetrafluoroethylene bottle followedby the addition of dried DMSO (20 mL), and heated at 60 C for 2.5-3 h. The reaction mixture was cooled to room temperature, treated with water (80 mL) and extracted with diethyl ether (100 mL). The organic layer was washed with water (3 ¡Á 25 mL), dried over Na2SO4, and purified by chromatography on silica gel with PE/EA (50:1-10:1) as eluent to give 9 as a white solid (1.27 g, yield 60%). 3,6-Difluoropyrazine-2-carbonitrile (9) Yield: 60%. white solid, M.p.: 58-60 C (Lit. 56-57 C, Li 2017). 1H NMR (400 MHz, CDCl3)delta 8.35 (dd, J = 8.1,1.4 Hz, 1H). 13C NMR (125 MHz, CDCl3):delta 159.73-157.69(d, J = 255 Hz), 157.64-155.62 (d, J = 252.5 Hz), 135.09 (dd, J = 41.6, 11.0 Hz), 114.04 (d, J = 35.8 Hz), 110.62 (d,J = 9.1 Hz). EI-MS m/z: 141 (M+, 100), 122 (M+, -F, 50),96 (M+, -F, -CN, 50).

Statistics shows that 356783-16-9 is playing an increasingly important role. we look forward to future research findings about 3,6-Dichloropyrazine-2-carbonitrile.

Reference:
Article; Guo, Qi; Xu, Mingshuo; Guo, Shuang; Zhu, Fuqiang; Xie, Yuanchao; Shen, Jingshan; Chemical Papers; vol. 73; 5; (2019); p. 1043 – 1051;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, 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. 113305-94-5

A solution of thiophosgene (1.86 g, 15 mmol) in THF (4 mL) is added dropwise to a solution of 5-aminopyrazine-2-carbonitrile (1.20 g, 10 mmol) and pyridine (2 mL) in CH2Cl2 (200 mL) and THF (25 mL) at room temperature. The reaction mixture is stirred at room temperature for 3 h. The mixture is concentrated and the crude product is diluted with ethyl acetate, filtered and concentrated to give the title compound.

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, 113305-94-5, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Farouz, Francine S.; Holcomb, Ryan Coatsworth; Kasar, Ramesh; Myers, Steven Scott; US2011/144126; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 132426-19-8, name is 2-Bromo-1-(pyrazin-2-yl)ethanone, 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 132426-19-8, 132426-19-8

Example 76N-(2-amino-phenyl)-4-[4-(4-pyrazin-2-yl-1H-imidazol-2-yl)-tetrahydro-pyran-4-yl]-benzamide; 4-(4-Cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester (1.0 g, 4.08 mmol) was suspended in 4.0N NaOH and heated at 110 C. for 1 hour. After the reaction was complete, 2N HCl was slowly added to form a precipitate. The precipitate was then filtered, dried under vacuum, and used for next step without purification. 4-(4-Carboxy-phenyl)-tetrahydro-pyran-4-carboxylic acid (0.4 g, 1.6 mmol) was dissolved in NMP. HATU (1.28 g, 2.1 eq) and DIPEA (0.8 mL, 3.0 eq) were added and stirred at 50 C. for 1 hour. The reaction mixture was cooled down to room temperature and benzyl alcohol (172 mg, 1.0 eq) was added. The reaction mixture was stirred at room temperature overnight. Saturated aqueous solution of NaHCO3 was added to the mixture and was then extracted with EtOAc. The organic phase was dried, evaporated and used for next step without further purification.To a solution of 4-(4-benzyloxycarbonyl-phenyl)-tetrahydro-pyran-4-carboxylic acid (0.3 g, 0.88 mmol) and 2-bromo-1-pyrazin-2-yl-ethanone (210 mg, 1.2 eq) in acetonitrile, TEA (0.18 mL, 1.2 eq) was added and heated in the microwave at 80 C. for 1 hour. The reaction mixture was evaporated and purified by silica gel chromatography (Hex:EtOAc 25:75). 4-(4-benzyloxycarbonyl-phenyl)-tetrahydro-pyran-4-carboxylic acid 2-oxo-2-pyrazin-2-yl-ethyl ester (0.3 g, 0.65 mmol), NH4OAc (110 mg, 2.2 eq) and 3 molecular sieves were mixed together in xylene and heated in the microwave at 160 C. for 1 hour. After the reaction was done, it was extracted with EtOAc and the organic phase was dried and evaporated to be used in the next step without further purifications.Hydrogenation of 4-[4-(4-pyrazin-2-yl-1H-imidazol-2-yl)-tetrahydro-pyran-4-yl]-benzoic acid benzyl ester (0.2 mg, 0.45 mmol) in EtOH, was carried out in the presence of excess Pd/C (10%, dry basis) at a pressure of 1 atmosphere. After 16 hours, the reaction mixture was filtered through a celite pad and washed with hot ethanol. The solution was evaporated and used for next step without further purification.The above acid was then coupled with 1,2-phenylenediamine in the presence of HATU and DIPEA in DMF and purified by reverse phase chromatography to give the title compound. MS found for C25H24N6O2 as (M+H)+ 441.21 1H NMR (400 MHz, dmso-d6): 1H-NMR (DMSO) delta: 10.42 (s, 1H), 9.32 (s, 1H), 8.68-8.64 (m, 2H), 8.37 (s, 1H), 8.07 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.4 Hz, 2H), 7.46-7.28 (m, 5H), 3.82-3.79 (m, 2H), 3.52-3.46 (m, 2H), 2.98-2.95 (m, 2H), 2.40-2.29 (m, 2H).

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, 2-Bromo-1-(pyrazin-2-yl)ethanone, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Melvin, JR., Lawrence S.; Graupe, Michael; Venkataramani, Chandrasekar; US2010/22543; (2010); 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. 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., 6966-01-4

K2CO3 (0.89 g, 6.46 mmol) was added to a solution of methyl 3-amino-6-bromopyrazine- 2-carboxylate (0.75 g, 3.23 mmol) in anhydrous DME (15 ml) in a pressure tube. Trimethylboroxine (0.99 ml, 3.56 mmol) was added then the resulting brown suspension was de-gassed by bubbling a stream of nitrogen through the reaction mixture for 5 min. Pd(dppf)2C (0.13 g, 0.16 mmol) was added then the pressure tube was flushed with nitrogen and sealed. The reaction was stirred at 100 C for 16 h then allowed to cool to RT. The resulting suspension was filtered then the solid thus obtained was washed with EtOAc (20 ml). The combined filtrate was concentrated in vacuo. The crude material was purified by flash column chromatography on a silica column (50 g). The column was eluted with EtOAc: heptane, increasing the gradient linearly from 0:100 to 50:50 over 10 column volumes. The desired fractions were combined and evaporated to yield the product as a light yellow solid (470 mg, 87%).1H NMR (250 MHz, DMSO-de) delta 8.18 (s, 1 H), 7.11 (s, 2H), 3.83 (s, 3H), 2.33 (s, 3H). LC/MS (System A): m/z (ESI+) = 168 [MH+], Rt = 0.68 min, UV purity = 100%.

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; ENTERPRISE THERAPEUTICS LIMITED; MCCARTHY, Clive; HARGRAVE, Jonathan David; HAY, Duncan Alexander; SCHOFIELD, Thomas Beauregard; WENT, Naomi; (111 pag.)WO2017/221008; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

23688-89-3, Adding some certain compound to certain chemical reactions, such as: 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, 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 23688-89-3.

To a 100 ml round bottom flask, 6-chloropyrazine-2-carboxylic acid (Ig, 6.31 mmol) was suspended in dry CH2Cl2 (30ml). Oxalyl chloride (3.78 ml, 7.57 mmol) was added along with a few drop of DMF, the mixture was stirred at room temperature for 12 hrs, N, O- Dimethylhydroxylamine hydrochloride (0.800 g, 8.20 mmol) was added, the resulting mixture was cooled down to 5C, TEA (2.64 ml, 18.92 mmol) was added via a droping funal, the reaction mixture was stirred at room temperature for 30 minutes, filtered and the filter cake was washed with EtOAc, the combinded filtrate was washed with saturated sodium bicarbonate and brine, concentrated to an oil, purified on silica gel with Hexanes/EtOAc solventsto give product (1.06g). MS (ES) MH+: 202 for C7H8ClN3O2

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 23688-89-3.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BARVIAN, Kevin; BASARAB, Gregory, Steven; GOWRAVARAM, Madhusudhan, Reddy; HAUCK, Sheila, Irene; ZHOU, Fei; WO2010/43893; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6863-73-6, A common compound: 6863-73-6, name is 3-Chloropyrazin-2-amine, 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.

EXAMPLE 1; Tert-butyl 4-(8-(2-fluoro-4-(methylsulfonyl)phenylamino)imidazo[l,2- a]pyrazin-3-yl)-5,6-dihydropyridine-l(2H)-carboxylateStep 1: 8-Chloroimidazo[l,2-a]pyrazine[0313] 3-chloropyrazin-2-amine (21.0 g, 161.54 mmol, 1.00 equiv) was dissolved in isopropyl alcohol (200 mL) in a 500 mL round-bottom flask equipped with a reflux condenser. To this solution was added 2-bromo-l,l-diethoxyethane (160.3 g, 813.71 mmol, 5.00 equiv) in small portions over 10 minutes. The resulting mixture was then allowed to reflux for 2 hours in an oil bath. The reaction was monitored by TLC (EtOAc/PE = 1:1). The mixture was cooled down to room temperature and filtered off to give a yellow cake. The solid was added to a saturated solution of NaHCC>;3 (200 mL) and DCM (IL). Aqueous layer was separated from organic phase and re-extracted with DCM (2x 250 mL). The combined organics were dried over MgSO4, filtered and evaporated to dryness affording 8-chloroimidazo[l,2-a]pyrazine (25 g) as a yellow solid.

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-Chloropyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; KALYPSYS, INC.; KAHRAMAN, Mehmet; SMITH, Nicholas, D.; BONNEFOUS, Celine; NOBLE, Stewart, A.; PAYNE, Joseph, E.; WO2010/88518; (2010); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 5521-58-4, name is 5-Methylpyrazin-2-amine, 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. 5521-58-4

1-Chloro-N,N,2-trimethyl-l-propenylamine (0.86 g, 6.56 mmol) was added to a solution of 3- [4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-(( 15)-2- {(tert-butyl( dimethyl)silyl]oxy} -1- methylethoxy)benzoic acid (3 g, 5.96 mmol) in DCM (100 mL) and stirred at RT for Ihour. 2- Amino-5-methylpyrazine (1.3 g, 11.9 mmol) and pyridine (0.94 mL, 11.9 mmol) were added and the reaction stirred for a further 30 mins. The solvent was removed in vacuo. Water (100 mL) was added and the mixture extracted with ethyl acetate (3 x 50 mL). The extracts were combined and washed with water (100 mL), brine (100 mL), dried (MgS04), filtered, and evaporated in vacuo to give the crude product which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (3.6 g). ?H NMR No. (CDC13): 0.00 (s, 3H), 0.03 (s, 3H), 0.81 (s, 9H), 1.30 (d, 3H), 2.32 (quin, 2H), 2.51 (s, 3H), 3.60-3.80 (m, 2H), 4.20-4.39 (brm, 4H), 4.45 (m, 1H), 6.75 (m, 1H), 7.03 (d, 2H), 7.21 (s, 1 H), 7.40 (d, 1 H), 7.50 (d, 1 H), 8.10 (s, 1 H), 8.27 (s, 1 H), 9.48 (s, 1 H). m/z 595 (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, 5521-58-4, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/121110; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4858-85-9, 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 4858-85-9 as follows.

2,3-Dichloropyrazine A-1 (15 g; 100.68 mmol) and hydrazine hydrate 65 % (15.509 ml; 201.37 mmol) are dissolved in 45 ml ethanol and stirred for 1 h at 80 C. While cooling down, a precipitate is formed. It is slurred up with a small amount of water and filtered off. It is washed with water and then dried to afford the product. Yield: 93% (13.6 g; 94.07mmol) HPLC-MS: (M+H)+ = 145/147; tRet = 0.34 min; method FECB5

According to the analysis of related databases, 2,3-Dichloropyrazine, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ENGELHARDT, Harald; WO2015/67770; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem