Month: October 2020

32111-21-0, A common compound: 32111-21-0, name is 2-Iodopyrazine, 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.

Step C: A solution of 5-(4-chloro-phenyl)-l-(3-methanesulfonyl-phenyl)-6-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-l,5-dihydro-pyrazolo[3,4-d]- pyrimidin-4-one (8, 0.5 g, 0.829 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (0.26 g, 1.2 mmol), cesium carbonate (0.54 g, 1.7 mmol), Pd(dppf>2Cl2 (0.06 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 100 0C for 3 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3 *). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by preparative HPLC to afford 5-(4-chloro-phenyl)-l-(3-methanesulfonyl-phenyl)-6-(4-pyrazin- 2-yl-phenyl)-l,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (9). 1H NMR (DMSO-d6, 400 MHz) delta 9.25 (s, IH), 8.71 (m, IH), 8.68 (m, IH), 8.63 (m, IH), 8.61 (m, IH), 8.55 (m, IH), 8.09 (m, 2H), 7.95 (m, IH), 7.88 (m, IH), 7.62 (m, 2H), 7.45 (m, 4H), 3.30 (s, 3H); LC-MS calculated for C28H19ClN6O3S (M+H*) 555.1, found 555.0.

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-Iodopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; IRM LLC; WO2007/120454; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5049-61-6,Some common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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.

Referring to Scheme 3, pyrazin-2-ylamine (1 g, 10.5 mmol) was dissolved in a solution of DMSO (40 ml)/H2O (1 ml) at 0 C. N-bromosuccinimide (3.93 g, 22 mmol) was added over an hour keeping the temperature below 5 C. Once addition was complete, the mixture was stirred for 6 hours at RT. The mixture was poured over ice water (150 ml) whilst stirring, then extracted with EtOAc (4¡Á100 ml). The organic layers were combined, dried and evaporated to leave an orange oil, which solidified overnight under high vacuum. 3,5-dibromopyrazin-2-amine was produced as an orange/brown solid (2.24 g, 84%). The product was used for the next reaction without further purification. [M+H] calc’d for C4H3Br2N3, 254; found, 254.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Pyrazin-2-amine, its application will become more common.

Reference:
Patent; Dong, Qing; Hosfield, David J.; Paraselli, Bheema R.; Scorah, Nicholas; Stafford, Jeffrey A.; Wallace, Michael B.; Zhang, Zhiyuan; US2006/84650; (2006); 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. 123-32-0, name is 2,5-Dimethylpyrazine, A new synthetic method of this compound is introduced below., 123-32-0

Preparation of 3,6-dimethyl-2- (3-chloro) benzoyl pyrazine, comprising the steps of:(1) 2,5-dimethyl pyrazine take 0.2mmol, 3- chloro-benzoyl formate 0.4mmol, silver phosphate 0.02mmol, potassium persulfate 0.4mmol, 1.4mL was added dichloromethane, 0.6mL distilled water after the mixture was made, and the mixture was placed in a reaction tube in 5mL, placed in an oil bath at 40 heated, the 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 37mg target The product, 74% yield.

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

5900-13-0, 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 5900-13-0 as follows.

5-bromo-3-methoxy-2-pyrazinamme (13.5g), hexane-2,5-dione (9g) and para- toluenesulphonic acid hydrate (0.5g) in toluene (200ml) was heated under reflux using a Dean and Stark trap to collect the water. After 16h, the solution was allowed to cool, EPO concentrated to 50ml and passed through a pad of silica gel eluting with dichloromethane to collect the subtitle compound. Yield 17g.1H NMR (D6-DMSO):8.25 (IH, s), 5.92 (2H, s), 4.02 (3H, s), 2.02 (6H, s)

According to the analysis of related databases, 5-Bromo-3-methoxypyrazin-2-amine, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; WO2007/35154; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

27398-39-6, Name is 3-Chloropyrazine-2-carboxylic acid, 27398-39-6, 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 4: 3-chloro-N-[[1 -r3-chloro-5-r2-(trifluoromethyl)cvclopropyll-2-Pyridyllcvclopropyllmethyllpyrazine-2-carboxamide (compound A.1 1 1 )147 mg [1 -[3-chloro-5-[2-(trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methanamine (step 3) was dissolved in 3 ml of dichloromethane and 0.142 ml triethylamine was added. After cooling to 0¡ãC, 193 mg 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride, 84 mg 3-chloropyrazine-2-carboxylic acid and 141 mg 1- hydroxybenzotriazole were added. The mixture was stirred overnight at ambient temperature. Then water was added. The layers were separated, the organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. Crude material was obtained as an orange oil, which was purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent. Thus, 161 mg of 3-chloro-N-[[1-[3-chloro-5-[2- (trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methyl]pyrazine-2-carboxamide was obtained as a yellow sticky solid. 1H-NMR (CDCI3): 8.42 ppm (d, 1 H), 8.38 ppm (d, 1 H), 8.18 ppm (s, 1 H), 7.78 ppm (s, 1 H, broad), 7.31 ppm (s, 1 H), 3.66 ppm (d, 1 H), 2.26 ppm (m, 1 H), 1 .78 ppm (m, 1 H), 1.57 ppm (m, 1 H), 1.39 ppm (m, 1 H), 1.18 ppm (m, 4H).

Statistics shows that 3-Chloropyrazine-2-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 27398-39-6.

Reference:
Patent; SYNGENTA PARTICIPATIONS AG; SYNGENTA LIMITED; PITTERNA, Thomas; LOISELEUR, Olivier; WORTHINGTON, Paul, Anthony; O’SULLIVAN, Anthony, Cornelius; LUKSCH, Torsten; BOBOSIK, Vladimir; WO2013/64521; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

41270-66-0, Name is 5-Chloro-2,3-diphenylpyrazine, 41270-66-0, 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.

2-[4-(tert-butoxycarbonyl)(isopropyl)aminobutoxy]-N-(methylsulfonyl)acetamide (20.0 g, 0.055 mol)And dissolved in methanol (110 mL),Trifluoroacetic acid (6.8 g, 0.06 mol) was added and the reaction stirred at 65 C for 6 hours until the reaction was complete. The reaction mixture was added dropwise to stirred water (200 mL), cooled to 0 C for 3 hours and filtered to give the intermediate compound 2- [4- (isopropyl) aminobutoxy] -N- (methylsulfonyl) acetamide) and then dissolved in methanol (40 mL)5-Chloro-2,3-diphenylpyrazine (16.0 g, 0.06 mol)N, N-diisopropylethylamine (15.5 g, 0.12 mol),The reaction mixture was stirred for 8 hours at 100 C. The reaction mixture was allowed to cool to room temperature. Water (40 mL) was added and the mixture was cooled to -10 C for 3 hours. The resulting mixture was filtered to give a solution of celecoxib (25.0 g) , The reaction of this step is as follows

Statistics shows that 5-Chloro-2,3-diphenylpyrazine is playing an increasingly important role. we look forward to future research findings about 41270-66-0.

Reference:
Patent; Hunan Ouya Biological Co., Ltd.; Li Xingmin; (10 pag.)CN105949135; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

24241-18-7, These common heterocyclic compound, 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, 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.

To a solution of intermediate I-82 (10 g, 40 mmol, 1.0 eq) in DMF (115 mL) was added neat triethylamine (53 mL), Pd(PPh3)4 (2.3 g, 2.0 mmol, 0.05 eq) and CuI (0.90 g, 4.7 mmol, 0.12 eq) followed by drop wise addition of ethynyltrimethylsilane (6.7 mL, 48 mmol, 1.2 eq) and the reaction mixture was stirred for 30 minutes at 120 C. The crude reaction mixture was concentrated by evaporation and the crude reaction product was purified by silica gel column chromatography to give intermediate I-83 (3.0 g, 17%) as yellow oil. MS (ESI): m/z 271 (M+H+).

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 24241-18-7.

Reference:
Patent; Chytil, Milan; Engel, Sharon R.; Fang, Qun Kevin; Spear, Kerry L.; US2010/204214; (2010); 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.

General procedure: Method B is a modification of Method A and was performed under nitrogen atmosphere andwith extended work-up. Substituted benzoyl chloride (1.5 mmol, 1.2 equiv) was placed into the askunder nitrogen, diluted with dry DCM (5 mL) and dry pyridine (400 mg, 5 mmol, 4 equiv) was added.The mixture was mixed for 5 min under nitrogen. Then, 5-chloropyrazin-2-amine (162 mg, 1.25 mmol,1 equiv) dissolved in DCM (10 mL) was added dropwise over 10 min under nitrogen ow. The askwas closed by septum and stirred for additional 6 h. After reaction, the mixture was diluted with DCMto the final volume of 40 mL and washed with water (1 30 mL), 5% (m/m) aqueous NaHCO3 solution(1 30 mL), and brine (1 30 mL). The organic layer was dried over anhydrous Na2SO4 and adsorbedon silica (4 g) by evaporating the solvents under reduced pressure. Automated flash chromatographywas run using same conditions as described in Method A. If needed, the products were recrystallizedfrom hot EtOH (crystallization initiated by cooling and dropwise addition of cold water).

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:
Article; Zitko, Jan; Mindlova, Al?b?ta; Vala?ek, Ond?ej; Jand’ourek, Ond?ej; Paterova, Pavla; Janou?ek, Ji?i; Kone?na, Klara; Dole?al, Martin; Molecules; vol. 23; 9; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 41270-66-0, name is 5-Chloro-2,3-diphenylpyrazine, molecular formula is C16H11ClN2, 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. 41270-66-0

Under the protection of nitrogen,Add 3-methyl-2-chloro-quinoxaline (532 mg, 2.00 mmol) to cis-5-(isopropylaminomethyl)tetrahydrofuran-2-yl)methanol (1.04 g, 6.00 mmol)N-methylpyrrolidone(50mL) solution,The reaction was heated to 190 C for 15 h, and the reaction was monitored by LC-MS.The reaction was cooled, and ice water was added to the mixture, and ethyl acetate (50mL*3)The organic mixed phase was washed with water (50 mL) and saturated brine (50 mL*2).Filtration, solvent removal under reduced pressure, purification by chromatography on silica gel column, and collected under reduced pressure.Drying in vacuo gave 641.5 mg of Compound VIII as a white solid.Yield: 79.6%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 41270-66-0, its application will become more common.

Reference:
Patent; Chengdu Yuandong Bio-pharmaceutical Co., Ltd.; Zeng Yanqun; Yan Shengyong; Zhang Tao; Wang Ying; (17 pag.)CN108623541; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 113305-94-5

4G. Benzyl-(2-{4-[(Z)-3-(5-cyano-yrazin-2-ylamino)-3-methylsulfanyl-acryloyl]-3- methoxy-henyl}-ethyl)-carbamic acid tert-butyl esterA solution of 2-amino-5-cyanopyrazine (0.12 g, 0.92 mmol) was added in portions to a stirred slurry of NaH (60% in mineral oil) (0.040 g, 0.92 mmol) in THE (3 mL) at room temperature. The mixture was stirred for 30 minutes then benzyl-{2-[4-(3,3-bis- methylsulfanyl-acryloyl)-3-methoxy-phenyl]-ethyl}-carbamic acid tert-butyl ester (0.30 g, 0.62 mmol) was added and the reaction mixture was then heated to 65C for 12hours. The solution was allowed to cool to room temperature then water (10 mL) was carefully added and the mixture extracted with EtOAc (3 x 20 mL). The combined organic extracts were washed with brine (10 mL), dried (Na2SO4) and evaporated under reduced pressure to leave a residue that was purified by column chromatography on neutral silica gel (60-120 mesh) using 15-30% EtOAc/hexanes asthe eluent to give the title compound (0.17 g, 49%).

The synthetic route of 113305-94-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ONCOTHYREON INC.; BOYLE, Robert, George; WALKER, David, Winter; BOYCE, Richard, Justin; PETERSON, Scott; FAROUZ, Francine; VO, Cong, Hung; WO2015/120390; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem