Month: November 2020

These common heterocyclic compound, 123-32-0, name is 2,5-Dimethylpyrazine, 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. 123-32-0

The method of preparing 3,6-dimethyl-2- (4-fluoro) benzoyl pyrazine, comprising the steps of:(1) 2,5-dimethyl pyrazine take 0.2mmol, 4- fluoro-benzoyl acid 0.4mmol, silver phosphate 0.02mmol, potassium persulfate 0.4mmol, 1.4mL was added dichloromethane, 0.6mL distilled water was added, and the mixture was placed in a reaction tube in 5mL, 40 oil bath was heated, reaction 24h, cooled to room temperature to obtain a reaction solution;(2) The step (1) the resulting reaction mixture was directly concentrated to give a concentrate, the concentrate with ethyl acetate / petroleum ether = 1/2 (v / v) as the developing solvent, separation by thin layer chromatography to give 34 mg desired product in 74% yield.

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 123-32-0.

Reference:
Patent; Henan Agricultural University; Wu Zhiyong; Zhao Mingqin; Li Yuan; (10 pag.)CN108101856; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 123-32-0 name is 2,5-Dimethylpyrazine, 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. 123-32-0

Intermediate 55 2-(chloromethyl)-5-methylpyrazine To a solution of 2,5-dimethylpyrazine (500 mg, 4.62 mmol) in carbon tetrachloride (7 mL) was added NCS (679 mg, 5.09 mmol) followed by BPO (20 mg) and the mixture was heated to 80 C for 6 hours. The mixture was diluted with DCM and extracted with saturated aqueous sodium sulfite solution and brine. The organic layer was dried and concentrated to give a crude product which was purified via silica gel chromatography eluting with petroleum ether/ ethyl acetate (1 :0 to 15: 1) to give 2-(chloromethyl)-5-methylpyrazine (133 mg, 20.19% yield) as yellow oil. LCMS retention time 0.557 min; LCMS MH+ 143.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,5-Dimethylpyrazine, and friends who are interested can also refer to it.

Reference:
Patent; HYDRA BIOSCIENCES, INC.; CHENARD, Bertrand; GALLASCHUN, Randall; WO2014/143799; (2014); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, 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. 55557-52-3

General procedure: In a degassed solution of DME/water 2:1 (12mLmmol-1 of diazine), was introduced S-Phos (10mol%) and Pd(OAc)2 (5mol%). The solution was heated at 80C for 10min and sodium carbonate (4equiv), the arylboronic species (1.05 or 1.50equiv) and 3-chloropyrazine-2-carbonitrile (1equiv) were added. The solution was then refluxed (15min or overnight) under argon. The resulting solution was filtrated on celite and washed with ethyl acetate and water. The aqueous phase was then extracted 3 times with ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated to dryness. The residue was purified by silica gel chromatography to give the desired product.

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 55557-52-3.

Reference:
Article; Fresneau, Nathalie; Dumas, Noe; Tournier, Benjamin B.; Fossey, Christine; Ballandonne, Celine; Lesnard, Aurelien; Millet, Philippe; Charnay, Yves; Cailly, Thomas; Bouillon, Jean-Philippe; Fabis, Frederic; European Journal of Medicinal Chemistry; vol. 94; (2015); p. 386 – 396;,
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

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

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

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

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

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

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