Month: December 2020

Synthetic Route of 33332-29-5, A common heterocyclic compound, 33332-29-5, name is 2-Amino-5-chloropyrazine, molecular formula is C4H4ClN3, 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.

Step 2: Synthesis of 2,5-dichloropyrazine To a stirred solution of 5-chloropyrazin-2-amine (1 g, 7.751 mmol) in conc. HCl (10 mL) was added aq. solution sodium nitrite (1.1 g, 15.89 mmol) at -10¡ã C. over a period of 1 h, stirred for 1 h 0¡ã C. and then at RT for 2 h. Progress of reaction was monitored by TLC. After reaction completion reaction mass neutralised with 50percent NaOH solution and extracted with DCM. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 2percent ethyl acetate in hexane as eluent to yield 2,5-dichloropyrazine (0.59 g, 15percent) as colourless oil. MS: 184.1 [M-1]

The synthetic route of 33332-29-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mankind Pharma Ltd.; Patil, Rakesh Ishwar; Verma, Jeevan; Shah, Dharmesh; Ali, Sazid; Bapuram, Srinivasa Reddy; Rai, Santosh Kumar; Kumar, Anil; (146 pag.)US2017/291910; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5521-58-4, name is 5-Methylpyrazin-2-amine, 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. Formula: C5H7N3

Palladium (II) acetate (lOmg) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene(40mg) were added to a mixture of S-4-chloro-6-methyl-2-{2-[3-(pyrid-2-yl)isoxazol-5- yl]pyrrolidin-l-yl}pyrimidine (272mg, 0.80mmol), 2-amino-5-methylpyrazine (85mg, 0.78mmol) and cesium carbonate in 1,4-dioxane (5ml) under nitrogen. The mixture was heated at 100C in a sealed vessel under microwave irradiation for 18 hours. The solution was allowed to cool, the insolubles were removed by filtration and the solvent was removed from the filtrate by evaporation. The residue was purified by column chromatography on silica gel eluting with EtOAc / hexane (25:75 increasing in polarity to 0:100). The purified product was triturated with ether and hexane and the solid collected by filtration to give the title compound (174mg, 53%); NMR (398K) 2.03-2.15 (2H, m), 2.15-2.20 (IH, m), 2.15 (3H, s), 2.35-2.45 (IH, m), 2.38 (3H, s), 3.70-3.75 (IH, m), 3.76-3.84 (IH, m), 5.45-5.55 (IH, m), 6.48 (IH, s), 6.65 (IH, s), 7.40-7.46 (IH, m), 7.85-7.90 (IH, m), 7.90-7.95 (IH, d), 8.10 (IH, s), 8.61-8.65 (IH, d), 9.10 (IH, s), 9.30-9.35 (IH, br s); m/z 415 [MH]+ .

The synthetic route of 5521-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/31745; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 109838-85-9, 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

[0487] To a dry-ice / acetone cooled solution of Scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), was dropwise added n-BuLi (2.5 M, 14.1 mL, 0.035 mol) for 30 min. After addition, the reaction was stirred at this temperature for 30 min, followed by dropwise addition of a solution of Scheme 5-8 compound S4 (13.6 g, 0.04 mol) in THF (20 mL). The reaction mixture was stirred at this temperature for another 30 min and allowed to stir at room temperature for 16 h. The reaction was quenched with aq. NHtCl (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic fractions were washed with brine, dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10: 1) to afford the title compound (6 g, yield 50.4%) and Scheme 5-8 compound S6 (4.8 g) was recovered.

The chemical industry reduces the impact on the environment during synthesis (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (325 pag.)WO2017/35405; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 914452-71-4, A common heterocyclic compound, 914452-71-4, name is 2-Bromo-6-methylpyrazine, molecular formula is C5H5BrN2, 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.

n-Butyllithium (2.5M solution in hexane, 2.57 mL, 6.43 mmol) was added dropwise to 2-bromo-6-methylpyrazine (1060 mg, 6.13 mmol) in DCM (6 mL) at -78 C under nitrogen. 4H-spiro[benzo[d]isoxazole-7,1′-cyclopropan]-5(6H)-one (500 mg, 3.06 mmol) in DCM (1.5 mL) was added dropwise after the mixture had been stirred for 30 min. The mixture was stirred at -78 C for 1.5 h under 2, quenched with sat. aq. NaHCCb (20 mL) and extracted with DCM (3 x 20 mL). The combined organic layers were washed with brine (1 x 25 mL), dried over Na2S04, fdtered and evaporated. The crude product was purified by silica gel chromatography (45 to 50% EtOAc in petroleum ether). Pure fractions were evaporated to dryness to afford 5-(6-methylpyrazin-2-yl)-5,6-dihydro-4H-spiro[benzo[d]isoxazole-7,1′-cyclopropan]-5-ol (200 mg, 25.4 %) as a yellow foam. XH NMR (400 MHz, CDCb) d ppm 0.58 (ddd, J = 9.2, 7.3, 4.0 Hz, 1H), 1.01 (ddd, J = 9.1, 7.3, 4.0 Hz, 1H), 1.35 (ddd, J = 9.8, 7.3, 3.9 Hz, 1H), 1.76 (ddd, J= 9.9, 7.3, 3.9 Hz, 1H), 2.58 (d, J= 7.5 Hz, 1H), 2.61 (s, 3H), 2.63 (d, J = 4.4 Hz, 1H), 2.85 (dd, J = 16.0, 1.5 Hz, 1H), 3.22 (d, J = 16.0 Hz, 1H), 4.14 (s, 1H), 8.13 (s, 1H), 8.45 (s, 1H), 8.61 (s, 1H). m/z (ES+), [M+H]+ = 258; HPLC (C05)tR = 0.663 min (92.3%).

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; MEDIMMUNE LIMITED; BARTHOLOMEUS, Johan; BUeRLI, Roland; JARVIS, Rebecca; JOHNSTONE, Shawn; OSTENFELD, Thor; TERSTIEGE, Ina; TRAVAGLI, Massimiliano; TURCOTTE, Stephane; (203 pag.)WO2019/122265; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 63286-28-2, 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. 63286-28-2 name is 2-Chloro-3-hydrazinylpyrazine, 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.

Intermediate b (5.0 g, 0.034 mol) was added to triethyl orthoformate (50 mL), and the reaction was carried out at 80 C. The reaction time was monitored with a plate. The reaction liquid was directly filtered with cold suction, and the filter cake was washed with petroleum ether. After the cake was dried, 4.8 g of a yellow powder was obtained with a yield of 90.1%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-3-hydrazinylpyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Jiangxi Science and Technology Normal University; Zhu Wufu; Zheng Pengwu; Liu Xiaobo; Xu Shan; Zhang Qian; Tang Qidong; Zhou Hualan; Wu Jinjin; Yuan Ping; Zhang Hongbo; (25 pag.)CN110407839; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 4774-14-5, name is 2,6-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. name: 2,6-Dichloropyrazine

General procedure: To the N,N-dimethylformamide (DMF) (4 mL) solution of N,N-dimethylethylenediamine (95 mL, 0.87 mmol) was added K2CO3 (0.19 g, 1.3 mmol). After the reaction mixture was stirred at room temperature (RT) for 30 min, 2,6-dichloropyrazine (0.10 g, 0.67 mmol) was added and the resulting reaction mixture was further stirred at RT for 12 h. After removal of solvent in vacuo, the residue was treated with dichoromethane. Insoluble impurities were removed by filtration. Removal of solvent in vacuo gave the product 0.095 g in 71 % yield;

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4774-14-5, its application will become more common.

Reference:
Article; Lee, Jinho; Park, Jongseong; Hong, Victor Sukbong; Chemical and Pharmaceutical Bulletin; vol. 62; 9; (2014); p. 906 – 914;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, 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 24241-18-7, Recommanded Product: 2-Amino-3,5-dibromopyrazine

Example 137 Step A: Ethanol (10.0 mL) and chloroacetaldehyde (2.6953 g of 50 % by weight solution in water, 17.17 mmol) were added into a pressure tube containing 2-amino-3, 5- dibromopyrazine (2.015 gm, 7.97 mmol). The heterogeneous reaction mixture was stirred at 70C. The reaction mixture assumed a homogenous appearance after heating began, and precipitation started to appear 3 h later. After a total of 22 h of heating, the reaction mixture was cooled to rt. The precipitate was filtered, washed with EtOH (-10 mL), and exposed to high vacuum to afford impure imidazopyrazine 137A as an ash- colored solid (1.699 g). lH NMR: 9.03 (s, 1H), 8.24 (d, J = 0.9, 1H), 7.91 (d, J = 1.2, 1H). (ESI) m/z (M+H) + = 277.79.

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-Amino-3,5-dibromopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2003/84959; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 21279-64-1, 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 21279-64-1 as follows.

General procedure: Comp. 1a and 2a were prepared using microwave reactor. Special thick-walled tubes intended for use in microwave reactor were filled with a mixture of corresponding starting comp. 1 or 2 (150 mg, 0.952 mmol), 25% aqueous ammonia (2 mL, in excess) and MeOH (2 mL). Tubes fitted with stirrer and closed with a special cap were inserted into the reactor. Reaction conditions for microwave-assisted synthesis were: output 200 W, temperature 95 C, reaction time 30 min using PowerMAX mode.

According to the analysis of related databases, 21279-64-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Servusova, Barbora; Paterova, Pavla; Mandikova, Jana; Kubicek, Vladimir; Kucera, Radim; Kunes, Jiri; Dolezal, Martin; Zitko, Jan; Bioorganic and Medicinal Chemistry Letters; vol. 24; 2; (2014); p. 450 – 453;,
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. 4774-14-5, name is 2,6-Dichloropyrazine, A new synthetic method of this compound is introduced below., Application In Synthesis of 2,6-Dichloropyrazine

A mixture of 2,6-dichloropyrazine (2.5 g, 16.8 mmol, 1.0 equiv),/?- ? toluenesulfonic acid (6.4 g, 33.6 mmol, 2.0 equiv), sodium iodide (20.0 g, 133.3 mmol, 8.0 equiv), 15-crown-5 (2.0 mL) and sulfolane (40 mL) was heated at 150 0C and stirred in a sealed tube for 2 hr. After cooling, water (100 mL) was added to the reaction mixture. The mixture was then neutralized with a saturated solution of sodium hydrogencarbonate, and washed with a saturated solution of sodium thiosulfate. The mixture was extracted with diethyl ether (5 x 100 mL). The ether extracts were dried (Na2SO4) and concentrated in vacuo. 2,6-Diiodopyrazine was precipitated with 10 mL of water, filtered, washed with water and pentane to provide a pale yellow powder after lyophilization (2.1 g, 38%). 1H NMR (400 MHz, CDCl3) delta 8.74 (s, 2H); MS (M+H)+ = 332, R1= 1.29 min.

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; NOVARTIS AG; NOVARTIS PHARMA GmbH; XENON PHARMACEUTICALS INC; WO2008/24390; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 723286-80-4,Some common heterocyclic compound, 723286-80-4, name is tert-Butyl 3-bromo-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate, molecular formula is C10H15BrN4O2, 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 solution of 0.090 g (0.297 mmol) of 3-BROMO-7- (TERT-BUTOXYCARBONYL)- 5,6, 7,8-tetrahydro [1, 2,4] triazolo [4,3-a] pyrazine (Example 15, Step D) in 3 mL of dioxane was added 0.0630 g (0.899 mmol) of sodium thiomethoxide, and the reaction mixture was heated at 100 C for 1 d. The reaction was diluted with dichloromethane and washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate, and concentrated in vacuo to afford the title compound. LC/MS 271.1 (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 tert-Butyl 3-bromo-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate, its application will become more common.

Reference:
Patent; MERCK & CO., INC.; WO2004/58266; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem