Pyrazines

Electric Literature of 32587-10-3, A common heterocyclic compound, 32587-10-3, name is 3-Aminopyrazine-2-carboxamide, molecular formula is C5H6N4O, 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.

(d) In 5 mL of trifluoroacetic acid was dissolved 100 mg of 3-amino-2-pyrazinecarboxamide. At an ice-cooled temperature, 10% fluorine gas (a fluorine gas diluted with nitrogen gas) was introduced at a rate of 45 mL per minute for a period of 36 minutes. Then, while elevating the temperature from the ice-cooled temperature to room temperature, nitrogen gas was introduced for one hour. The reaction mixture was concentrated under reduced pressure to obtain 305 mg of an oily product. Of the oily product thus obtained, a 251 mg portion was dissolved in 9.3 mL of water and heated under reflux for 4 hours, The liquid reaction mixture was cooled to room temperature, and the deposited precipitate was filtered off. The filtrate was concentrated under reduced pressure, and the solid product thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=2:1] to obtain 9 mg of 3-amino-6-fluoro-2-pyrazinecarboxamide as a solid product.

The synthetic route of 32587-10-3 has been constantly updated, and we look forward to future research findings.

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

Some common heterocyclic compound, 19745-07-4, name is 2,5-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. Recommanded Product: 19745-07-4

A mixture of methyl (R)-3-(3-amino-4-(isobutyl(tetrahydro-2H-pyran-4-yl)amino)phenyl) butanoate (120 mg, 0.34 mmol), 2,5-dichloropyrazine (104 mg, 0.69 mmol), Pd2(dba)3 (32.5 mg, 0.036 mmol), Xantphos (40 mg, 0.07 mmol) and K2C03 (143 mg, 1 .03 mmol) in toluene (5 mL) was stirred at 100¡ãC under N2 atmosphere overnight. The resulting mixture was partitioned between EtOAc and H20. The organic layer was washed with brine, dried over Na2S04, filtered and concentrated to give the crude product which was purified by flash chromatography (silica gel, 0-50percent EtOAc in PE) to afford the title compound (120 mg, 76percent yield). LCMS (ESI) m/z calcd for C^HssCIN^Os: 460.22. Found: 461 .41 /463.36 (M/M+2)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19745-07-4, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; DE LA ROSA, Martha Alicia; KAZMIERSKI, Wieslaw Mieczyslaw; SAMANO, Vicente; (369 pag.)WO2018/116107; (2018); A1;,
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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. 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Formula: C5H2BrF3N2

Description 67: 1,1-dimethylethyl (lR,4S,6R)-4-({[5-(trifluoromethyl)-2- pyrazinyl]oxy}methyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate (D67); To a solution of 1,1-dimethylethyl (lR,4S,6R)-4-(hydroxymethyl)-3- azabicyclo[4.1.0]heptane-3-carboxylate D20 (120 mg) and 2-bromo-5- (trifluoromethyl)pyrazine D66 (120 mg) in DMF (4 ml) at 00C (ice bath) was added NaH (31.7 mg, 0.792 mmol) (gas evolution). The reaction mixture was slowly warmed to room temperature and stirred at room temperature for 1 hour. The reaction was quenched by a slow and careful addition of a saturated aqueous solution of NaHCO3 (40 ml). The organic phase was extracted with DCM (3×50 ml); the joined organic phase was washed with water and brine, dried over Na2SO4, filtered and concentrated to give the crude material. This was purified by Silica Chromatography (Biotage SP – column size 25 g) using Cy/EtOAc 90:10 as eluent. The appropriate fractions were concentrated to obtain the title compound D67 (62 mg).UPLC (Basic GEN_QC): rt = 1.07 minutes, peak observed: 374 (M+l) C17H22F3N3O3 requires 374.

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 1196152-38-1.

Reference:
Patent; GLAXO GROUP LIMITED; AMANTINI, David; DI FABIO, Romano; WO2010/122151; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 33332-29-5, name is 2-Amino-5-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. name: 2-Amino-5-chloropyrazine

General procedure: Isoquinolin-3-amine (3.23 g, 22.4 mmol) was added to a solution of 1,1′-thiocarbonyldipyridin-2(1H)-one (5.20 g, 22.4 mmol) in dichloromethane (50 mL) at room temperature. The reaction was stirred for 2 h, then purified by flash chromatography on silica gel (0-10% ethyl acetate in hexanes). Product fractions were combined and concentrated in vacuo to give 3-isothiocyanatoisoquinoline(3.9 g, 93 %) as a white solid.

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

Reference:
Article; Iwuagwu, Christiana; King, Dalton; McDonald, Ivar M.; Cook, James; Zusi, F. Christopher; Hill, Matthew D.; Mate, Robert A.; Fang, Haiquan; Knox, Ronald; Gallagher, Lizbeth; Post-Munson Amy Easton, Debra; Miller, Regina; Benitex, Yulia; Siuciak, Judy; Lodge, Nicholas; Zaczek, Robert; Morgan, Daniel; Bristow, Linda; Macor, John E.; Olson, Richard E.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 5; (2017); p. 1261 – 1266;,
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Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 14667-55-1, name is 2,3,5-Trimethylpyrazine, molecular formula is C7H10N2, 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. Computed Properties of C7H10N2

Example 10 [00650] Preparation of Cpd 76 [00651] The bromoketone intermediate obtained in Step C, Example 6 (855 mg, 3.0 mmol) was mixed with 2,3,5-trimethylpyrazine (402 mg, 3.3 mmol) and acetonitrile (10.0 mL) in a sealed tube. The mixture was stirred at 80 C for 4 hr and cooled to room temperature, followed by the addition of triethylamine (1.3 mL, 9.0 mmol). After stirring for 0.5 hours at room temperature, the mixture was stirred at 60 C overnight. The solvent was removed on a rotovap and the residue was chromatographed (silica gel, ethylacetate in dichloromethane 30%) to provide the intermediate, 3-(l,3-dimethylpyrrolo[l,2-a]pyrazin-7-yl)-7-fluoro-lH-isochromen-l- one (782 mg, 85%). MS m/z 309.3 [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 14667-55-1, its application will become more common.

Reference:
Patent; PTC THERAPEUTICS, INC.; CHEN, Guangming; DAKKA, Amal; KARP, Gary Mitchell; LI, Chunshi; NARASIMHAN, Jana; NARYSHKIN, Nikolai; WEETALL, Maria L.; WELCH, Ellen; ZHAO, Xin; WO2013/112788; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 76537-18-3, 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 76537-18-3 as follows.

Zinc dust (activated by the procedure found in WO2011/143365, the disclosure of which is incorporated herein by reference in its entirety) (0.627 g, 9.59 mmol) was charged to a dry flask and suspended in DMA (2.5 mL). 1,2-Dibromoethane (0.031 mL, 0.36 mmol) and TMSCl (0.092 mL, 0.72 mmol) were added and the reaction was stirred for 25 min. tert-Butyl 3-iodoazetidine-1-carboxylate (2.04 g, 7.20 mmol, Oakwood) in DMA (6.0 mL) was added slowly to the mixture which was immersed in a water bath to keep the temperature below 65 C. The mixture was stirred for 1 hour and was degassed by bubbling a stream of nitrogen through the mixture for 5 minutes. (0976) A separate flask was charged with 3-bromo-5-chloropyrazin-2-amine (0.50 g, 2.4 mmol, D-L Chiral Chemicals), dichloro[1,1?-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.118 g, 0.144 mmol) and copper(I) iodide (0.057 g, 0.30 mmol). DMA (6.0 mL) was added, and the mixture was degassed by bubbling a stream of nitrogen through the mixture for 5 minutes. The solution containing the organozinc in DMA was added, excluding any remaining zinc solids. The reaction mixture was then heated at 80 C. for 30 min. Upon cooling to room temperature, the reaction mixture was partitioned between water and EtOAc. The aqueous layer was extracted with two additional portions of EtOAc. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-100% EtOAc in hexanes to afford product (0.62 g, 90%). LCMS calculated for C12H18ClN4O2(M+H)+: m/z=285.1, found: 285.1. 1H NMR (400 MHz, CDCl3) delta 7.96-7.90 (s, 1H), 4.78-4.65 (s, 2H), 4.35-4.22 (m, 4H), 3.79-3.69 (p, J=7.4 Hz, 1H), 1.48-1.44 (s, 9H).

According to the analysis of related databases, 76537-18-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Incyte Corporation; Shepard, Stacey; Combs, Andrew P.; Falahatpisheh, Nikoo; Shao, Lixin; (96 pag.)US2019/276435; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference 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.

Intermediate 245 5-methyl-3 -phenyl- 1 -(pyrazin-2-yl)- 1 H-pyrazol-4-amine [00611] Step A: 2-(5-methyl-4-nitroso-3-phenyl- 1 H-pyrazol- 1 -vDpyrazine. To a solution of 2-hydrazinylpyrazine (0.485 g, 4.40 mmol) in HOAc (6 mL) was added (2- (hydroxyimino)-l-phenylbutane-l,3-dione (0.765 g, 4.00 mmol) in small portions over 2 minutes. The mixture was stirred for 5 minutes and the resulting light orange suspension was stirred at 60 C for 6 hours. EtOH (1 mL) was added and the mixture was heated at 60 C for an additional 6 hours. The resulting dark green suspension was cooled to ambient temperature and the mixture was diluted with H20 (30 mL). The green suspension was stirred for 1 hour and the solid was collected via vacuum filtration. The collected solid was washed with 0 and dried in vacuum. The solid was suspended in EtOH (25 mL) and concentrated HC1 (500 ) was added. The mixture was heated at reflux for 20 hours, cooled to ambient temperature and diluted with chilled H20 (75 mL). The mixture was treated with 1M NaOH to pH=7 and was extracted with Et20 (3X). The combined extracts were washed with saturated NaCl and dried over MgS04. The dried solution was filtered through packed Celite and concentrated. The residual green-yellow solid was purified on a Si02 column using step gradient elution (25% CH2C12, 50% EtOAc/hexanes) to furnish the title compound as a turquoise solid (325 mg, 31%). MS (apci) m/z = 266.1 (M+H).

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; ARRAY BIOPHARMA INC.; ALLEN, Shelley; BRANDHUBER, Barbara J.; CONDROSKI, Kevin Ronald; HUANG, Lily; KERCHER, Timothy; WINSKI, Shannon L.; WO2014/78408; (2014); 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. 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, A new synthetic method of this compound is introduced below., HPLC of Formula: C8H12N2O

Were added 2-hydroxymethyl-3,5,6-trimethyl pyrazine in 250mL three-necked flask (9.5g, 62.5mmol), MnO2(16.2g, 187.5mmol), ethanol 100mL, refluxed for 12h, TLC (petroleum ether – ethyl acetate 2: 1) detecting the reaction is substantially complete, cooled, filtered, recovering ethanol under reduced pressure to give a yellow solid by silica gel column chromatography (petroleum ether – ethyl acetate 4: 1) to give 8.8 g of a pale yellow solid, yield 93.9%.

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; Anhui University of Chinese Medicine; Hefei Medical Engineering Pharmaceutical Co., Ltd.; Hefei Enruite Pharmaceutical Co., Ltd.; Li Jiaming; He Guangwei; Zhang Yang; Huang Weijun; Zhang Yanchun; Liu Weizhong; Zuo Jian; Liu Huicai; Zhu Panhu; Wang Yujun; (14 pag.)CN106518791; (2017); A;,
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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 33332-25-1

Methyl 5-(chloropyrazine)-2-carboxylate (36 7) (2g, 0.0115mmol) was dissolved in 80mL of 87 DMSO. 88 Sodium azide (3g, 0.0463mmol) and 39 triphenylphosphene (4.6g, 0.1738mmol) were added and the mixture was refluxed at 120C for 4h. 20mL of 1N 89 HCl was added and the reaction was continued at 120C for 2h. The mixture was cooled and neutralized by using 90 aqueous NaHCO3 solution and 91 product was extracted in ethyl acetate, dried using Na2SO4. The ethyl acetate fraction was evaporated and washed with n-pentane to get 0.7g (yield 39.5%) yellow solid of compound 8. 1H NMR (400MHz, DMSO-d6) delta 8.53 (d, J=1.2Hz, 1H), 7.91 (d, J=1.2Hz, 1H), 7.39 (s, 2H), 3.79 (s, 3H). C6H7N3O2 [M]: 153.14; MS (ESI) m/z: [M-H]+: 152.05.

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; Trivedi, Prakruti; Adhikari, Nilanjan; Amin, Sk. Abdul; Jha, Tarun; Ghosh, Balaram; European Journal of Pharmaceutical Sciences; vol. 124; (2018); p. 165 – 181;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 68774-77-6, 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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

[0538] To a mixture of (R)-5-(2-(4-aminopiperidin-1-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one hydrochloride(60 mg, 0.16 mmol) and 5-cyano-2-fluoropyridine (20 mg, 0.16 mmol) in N-methylpyrolidinone (550 ml) was addedDIEA (57 ml, 0.33 mmol) in a microwave tube at room temperature. The tube was sealed and heated at 100C for 4 h.The mixture was cooled and partitioned between EtOAc/hexanes (2:1) and water. The aqueous layer was extractedwith EtOAc (2x). The combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated. Theresulting residue was purified by prep TLC (silica gel, 10% MeOH/DCM) to provide (R)-6-(1-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperidin-4-ylamino)nicotinonitrile. 1H-NMR (CDCl3, 500 MHz), delta 8.39 (m, 1H),7.82 (s, 2H), 7.60 (m, 1H), 6.41 (m, 1H), 5.29 (s, 2H), 4.92 (m, 1H), 3.23 (m, 1H), 2.96 (m, 1H), 2.39-2.46 (m, 4H), 2.18(s, 3H), 2.02 (m, 4H); LC-MS (IE, m/z): 393 [M + 1]+:_[0544] (R)-5-(2-(4-([1,2,4]Triazolo[4,3-a]pyrazin-8-ylamino)piperidin-1-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one was prepared in a similar fashion to that described for the synthesis of EXAMPLE 111 starting from (R)-5-(2-(4-aminopiperidin-1-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one hydrochloride and 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine. LC-MS (IE, mlz): 409 [M + 1]+.

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, 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Merck Sharp & Dohme Corp.; WALSH, Shawn; PASTERNAK, Alexander; CATO, Brian; FINKE, Paul, E.; FRIE, Jessica; FU, Qinghong; KIM, Dooseop; PIO, Barbara; SHAHRIPOUR, Aurash; SHI, Zhi-Cai; TANG, Haifeng; (136 pag.)EP2755656; (2016); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem