Category: Pyrazines

1458-18-0, A common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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: To a solution of methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate (1.0 eq.) in 2-propanol (5 mL/mmol), an appropriate primary or secondary amine(3-6 eq.) was added, and the reaction mixture wasrefluxed for 2 h.10) The solution was cooled to roomtemperature, concentrated under reduced pressure, andthe residue was purified by silica-gel column chromatography(Wako gel C-200, 30-40% ethyl acetate/n-hexane) to afford the series 1 intermediate (yield:32-95%). The regioselectivity of the nucleophilicsubstitution at the 5-position of the pyrazine ring wasconfirmed by an X-ray structural analysis (Fig. S1).

The synthetic route of 1458-18-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Murai, Masatoshi; Habu, Sayako; Murakami, Sonomi; Ito, Takeshi; Miyoshi, Hideto; Bioscience, Biotechnology and Biochemistry; vol. 79; 7; (2015); p. 1061 – 1066;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-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. 767340-03-4

Into a 500 ml flask were charged chloro(l,5-cyclooctadiene)rhodium(I) dimer{[Rh(cod)Cl]2}(292 mg, 1.18 mmol) and (R,S) f-butyl Josiphos (708 mg, 1.3 mmol) under a nitrogen atmosphere. Degassed MeOH was then added (200 mL) and the mixture was stirred at room temperature for 1 h. Into a 4 L hydrogenator was charged the enamine amide 2^4 (118 g, 0.29 mol) along with MeOH (1 L). The slurry was degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen gas at 50 0C for 13 h. Assay yield was determined by EtaPLC to be 93% and optical purity to be 94% ee. The optical purity was further enhanced in the following manner. The methanol solution from the hydrogenation reaction (18 g in 180 mL MeOH) was concentrated and switched to methyl t- butyl ether (MTBE) (45 mL). Into this solution was added aqueous Eta3PO4 solution (0.5 M, 95 mL).After separation of the layers, 3NNaOH (35 mL) was added to the water layer, which was then extracted with MTBE (180 mL + 100 mL). The MTBE solution was concentrated and solvent switched to hot toluene (180 mL, about 75 0C). The hot toluene solution was then allowed to cool to 0 0C slowly (5 – 10 h). The crystals were isolated by filtration (13 g, yield 72%, 98 – 99% ee); m.p. 114.1 – 115.7 0C. EPO lH NMR (300 MHz, CD3CN): delta 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2.68(m), 2.49 (m), 1.40 (bs).Compound Z1I exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon- 13 signals are not well resolved: 13c NMR (CD3CN): delta 171.8, 157.4 (ddd , JCF = 242.4, 9.2, 2.5 Hz), 152.2 (major), 151.8 (minor), 149.3(ddd; JCF = 246.7, 14.2, 12.9 Hz), 147.4 (ddd, /CF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JCF= 38.8 Hz), 124.6 (ddd , JCF= 18.5, 5.9, 4.0 Hz), 120.4 (dd , JCF= 19.1, 6.2 Hz), 119.8 (q, JCF= 268.9 Hz), 106.2 (dd , /CF = 29.5, 20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38.5 (minor), 36.9.

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, 767340-03-4, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK & CO., INC.; WO2006/119260; (2006); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

3149-28-8, Adding some certain compound to certain chemical reactions, such as: 3149-28-8, name is 2-Methoxypyrazine, 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 3149-28-8.

To a solution of 2-methoxypyrazine (5.0g, 45.4mmol), in 40ml of anhydrous THF was added tributyltin hydride (15.0mL, 54.9mmol) and the resulting solution stirred under nitrogen at 0C. Cyclohexylcarbonyl chloride (8.0mL, 59.8mmol) was added over 10min and stirring continued until reaction completion in 20min as determined by TLC (neutral alumina, EtOAc/hexanes (1/19, v/v)). A 1M solution of HCl in methanol (20.0mL) was then added to the reaction mixture that was stirred under nitrogen at 0C until reaction completion in 30min as determined by TLC (SiO2, EtOAc/hexanes (2/3, v/v). The reaction mixture was quenched with 50mL of water, extracted with ethyl acetate (3¡Á50mL), washed with saturated sodium bicarbonate (10mL), and then dried over anhydrous Na2SO4. Purification by silica gel flash column chromatography (100% hexanes: to remove tin by-products, followed by methanol / dichloromethane 2-5%) afforded 4-cyclohexanecarbonyl-1,2-dihydro-2-pyrazinone 3 (8.9g, 94%) as a pale yellow solid (mp 160-163C dec).

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 3149-28-8.

Reference:
Article; Williams, Alfred L.; St. Hilaire, Valentine R.; Tetrahedron; vol. 73; 48; (2017); p. 6712 – 6717;,
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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., 5049-61-6

NBS (100 g, 561.8 mmol) was added in small portions to a stirred solution of 2-aminopyrazine (25 g, 263 mmol) in dichloromethane (600 ml) over a period of 1 hour. The reaction was stirred at r.t. for Ih and washed with water. The organic phase was dried (MgStheta4) and evaporated. The crude product was filtered through a plug of silica using 2.5% MeOH in dichloromethane as the elu- ent.Yield 25 g (38%). HPLC 99% (System A). MS (electronspray) M+H+ m/z 254.4. IH NMR (400 MHz, CHLO ROFORM-D) delta ppm 5.04 (s, 2 H) 8.03 (s, 1 H).

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; BIOVITRUM AB (PUBL); WO2007/147874; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common heterocyclic compound, 873-42-7, name is 2-Amino-3,5-dichloropyrazine, molecular formula is C4H3Cl2N3, 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. 873-42-7.

Into a flask, under an inert atmosphere of nitrogen, was placed 1,1,1,2,2-pentafluoro-4-iodobutane (21.7 g, 79 mmol), zinc metal (8.4 g, 128 mmol) and DMA (60 mL). This was followed by the dropwise addition of a solution of iodine (0.77 g, 3.05 mmol) in DMA (4 mL). The resulting mixture was stirred for 3 h at 80C. The reaction was cooled and directly used in the next step. In a flask, under an inert atmosphere of argon, was added 3,5-dichloropyrazin-2-amine (10.0 g, 61.0 mmol) and Pd(PPh3)2Cl2 (4.3 g, 6.1 mmol). The resulting mixture was allowed to stir for 1 h at RT. The intermediate from Step A (65 mL, 79 mmol) was added and the resulting solution was warmed at 45C for 3 h. The reaction was then quenched by the addition of sat. aq. NH4Cl. The resulting solution was extracted with EtOAc (3X), and the organic layers combined, washed with brine, dried over anhydr. Na2SO4, and filtered. The filtrate was conc. in vacuo to dryness. The residue was purified RP-HPLC with acetonitrile:water (0.2% TFA) to afford the title compound.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; BERGER, Raphaelle; DONG, Guizhen; RAGHAVAN, Subharekha; YANG, Zhiqiang; (179 pag.)WO2017/200857; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

33332-29-5, Name is 2-Amino-5-chloropyrazine, 33332-29-5, 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.

Step A: S,S-Dimethyl-N-(5-chloropyrazin-2-yl)sulfilimine (5) Compound 5 is prepared from 2-amino-5-chloropyrazine as described above for 2 in Example 1A to afford pure 5 as a smelly, tan solid, m.p. 119-120.

Statistics shows that 2-Amino-5-chloropyrazine is playing an increasingly important role. we look forward to future research findings about 33332-29-5.

Reference:
Patent; Merck & Co., Inc.; US4609659; (1986); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19838-08-5,Some common heterocyclic compound, 19838-08-5, name is 3-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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.

3-Methyl-pyrazin-2-ylamine (2) (109 mg, 1.0 mmol), benzaldehyde (106 mg, 1.0 mmol) and 3-chloro- phenylisonitrile (138 mg, 1.0 mmol) were dissolved in a mixture of dry methanol (2.0 mL) and trimethyl orthoformate (2.0 mL) under argon. The mixture was stirred at 60C for 3 hours, then cooled to rt. An analytically pure sample of 3 was obtained from the crude product using preparative HPLC

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19838-08-5, its application will become more common.

Reference:
Patent; ESBATECH AG; WO2005/120513; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

55557-52-3, 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 55557-52-3 as follows.

The 3 – chloro -2 – cyanopyrazine (2.24 g 1.6 eq), 4 – amino -2 – pyrimidine formic acid (1.39 g 1 eq) and potassium carbonate (4.1 g 3 eq) solution 20 mLDMF in, stirring and heating to 60 C, reaction 5 h, cooling to room temperature, filter, solution (DCM/MeOH=20:1) for refining, yellow solid product to be 1.73 g (yield: 71%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 55557-52-3, and friends who are interested can also refer to it.

Reference:
Patent; Jiangxi Runze Pharmaceutical Co., Ltd.; Liao Niansheng; Zou Mingming; Hu Xiande; Sui Rongchun; Xu Man; (14 pag.)CN108689997; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 123-32-0, name is 2,5-Dimethylpyrazine, molecular formula is C6H8N2, 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. 123-32-0

(b) 3,6-Dimethylpyrazin-2-amine A mixture of 2,5-dimethylpyrazine (14 g, 0.13 mol) in N,N-dimethylaniline (50 mL) was heated to 170 C. and NaNH2 (22 g, 0.56 mol) was added in portions. The reaction mixture was stirred at 170 C. for 1 h, and the solvent was removed. The product was purified by silica gel column chromatography to give 3,6-dimethylpyrazin-2-amine as a brown solid (1.6 g, yield 10%). ESI MS: m/z 124 [M+1]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 123-32-0, its application will become more common.

Reference:
Patent; Sunovion Pharmaceuticals Inc.; US2012/178748; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

113305-94-5, Adding some certain compound to certain chemical reactions, such as: 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, 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 113305-94-5.

Synthesis 2C (R)-tert-Butyl 2-((2-(5-cyanopyrazin-2-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)methyl)morpholine-4-carboxylate (R)-tert-Butyl 2-((2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)methyl)morpholine-4- carboxylate (1.44 g, 3.64 mmol), 2-amino-5-cyanopyrazine (0.612 g, 5.09 mmol, 1.4 eq.), tris(dibenzylideneacetone)dipalladium(0) (0.267 g, 0.291 mmol, 0.08 eq.), rac-2,2′- bis(diphenylphosphino)-1 ,1 ‘-binaphthyl (0.362 g, 0.582 mmol, 0.16 eq.) and caesium carbonate (2.37 g, 7.28 mmol) were suspended in anhydrous dioxane (33 ml_) under argon. Argon was bubbled through the mixture for 30 minutes, after which the mixture was heated to 100C for 22 hours. The reaction mixture was cooled and diluted with dichloromethane, then absorbed on to silica gel. The pre-absorbed silica gel was added to a 100 g KP-Sil SNAP column which was eluted with 20-50% ethyl acetate in hexanes to give the partially purified product as an orange gum. The crude product was dissolved in dichloromethane and purified by column chromatography on a 90 g SingleStep Thomson column, eluting with 20% ethyl acetate in dichloromethane, to give the title compound (1.19 g, 68%). H NMR (500 MHz, CDCI3) delta 1.50 (9H, s), 2.71-2.88 (1 H, m), 2.93-3.08 (1 H, m), 3.27- 3.32 (1 H, m), 3.40-3.44 (1 H, m), 3.55-3.64 (1 H, m), 3.71-3.77 (1 H, m), 3.82-4.11 (3H, m), 5.33 (1 H, broad s), 7.19 (1 H, s), 8.23 (1 H, s), 8.58 (1 H, s), 8.84 (1 H, s). LC-MS (Agilent 4 min) Rt 2.93 min;m/z (ESI) 480 [MH+].

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 113305-94-5.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; COLLINS, Ian; MATTHEWS, Thomas Peter; FARIA DA FONSECA MCHARDY, Tatiana; OSBORNE, James; LAINCHBURY, Michael; WALTON, Michael Ian; GARRETT, Michelle Dawn; WO2013/171470; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem