Category: Pyrazines

Application of 4949-13-7, These common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, 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 5: N-((4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (8e) To a microwave vial were added N-((4S,6S)-4-(2-fluoro-5-hydroxyphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (95 mg, 0.229 mmol), 2-fluoro-pyrazine (24.74 mg, 0.252 mmol), cesium carbonate (90 mg, 0.275 mmol) in DMSO (459 muL). The vial was heated in microwave instrument at 100 C. for 30 min. After cooling to room temperature, water was added to the reaction mixture and precipitate was observed. After stirring for 10 min, the precipitate was collected by filtration, washed with water and hexane, dried in vacuum oven at 60 C. for 1 h to provide N-((4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (85 mg, 0.173 mmol, 75% yield) as off-white solid. MS m/z=493 [M]+. Calculated for C23H17F5N4O3: 492.4.

Statistics shows that 2-Fluoropyrazine is playing an increasingly important role. we look forward to future research findings about 4949-13-7.

Reference:
Patent; MINATTI, Ana Elena; LOW, Jonathan D.; ALLEN, Jennifer R.; CHEN, Jian; CHEN, Ning; CHENG, Yuan; JUDD, Ted; LIU, Qingyian; LOPEZ, Patricia; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; TAMAYO, Nuria A.; XUE, Qiufen; YANG, Bryant; ZHONG, Wenge; US2014/249104; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 14508-49-7,Some common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, molecular formula is C4H3ClN2, 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.

2-Chloropyrazine (7.79 mL, 87 mmol, commercially available e.g. from Sigma- Aldrich or Haiso PharmChem) was dissolved in ethanol (50 mL), and hydrazine hydrate (6.85 mL, 218 mmol) was added. The solution was refluxed for 6 hours. The mixture was cooled to room temperature and the solvent was partially evaporated. The residue was diluted with water and extracted with 10% (v/v) of 2-propanol/Dichloromethane solution (5 extractions). The combined organic phases were then dried and evaporated to give a yellow solid which was triturated with diethyl ether to give 2-hydrazinopyrazine as a yellow solid (3.32 g).

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

Reference:
Patent; GLAXO GROUP LIMITED; DEAN, David Kenneth; MUNOZ-MURIEDAS, Jorge; SIME, Mairi; STEADMAN, Jon Graham Anthony; THEWLIS, Rachel Elizabeth Anne; TRANI, Giancarlo; WALTER, Daryl Simon; WO2010/125102; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 1094070-46-8 as follows. Formula: C8H9N3S

Part D: To a DMF (400 mL) solution of compound from Example 1 , Part C (21.8 g) was added N-iodosuccinimide (26.9 g) and the resulting mixture was heated overnight at 6OC. The mixture was concentrated and water (400 mL) was added. After stirring 1 hr at rt, saturated sodium carbonate was added (250 mL) and subsequently stirred an additional 30 min at rt. The mixture was filtered, washed with water, methanol (100 mL) and the filter cake was dried overnight under vacuum. A brown solid was obtained (31.4 g, 87%).

According to the analysis of related databases, 1094070-46-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SCHERING CORPORATION; ALBANY MOLECULAR RESEARCH, INC.; WO2009/97233; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 88625-24-5, A common heterocyclic compound, 88625-24-5, name is 5-Chloropyrazine-2-carbaldehyde, molecular formula is C5H3ClN2O, 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.

3,3-Difluoropiperidine hydrochloride [CAS RN: 496807-97-7] (531 mg, 3.37 mmol,1.6 eq), 5-chloropyrazine-2-carbaldehyde [CAS RN: 88625-24-5] (300 mg,2.11 mmol, 1.0 eq) and sodium triacetoxyborohydride (1.43 g, 6.74 mmol,3.2 eq) were suspended in 20 mL 1,2-dichloroethane. Then, triethylamine (0.59 mL, 4.21 mmol, 2.0 eq) was added and the reaction mixture was stirred at rt overnight. Then, water was added. After stirring for 10 mm, the resulting phases were separated by the use of a Whatman filter. The volatile components of theorganic phase were removed in vacuo and the crude material was purified via preparative MPLC (Biotage Isolera; 25 g SNAP cartridge: hexane/ethyl acetate 9/1 -> hexane/ethyl acetate 1/1) to give 340 mg (58% yield of theory) of the title compound.UPLC-MS (Method 2): R = 1.09 mm; MS (EI0): m/z = 248 [M+H].1H-NMR (400 MHz, DMSO-d6): oe [ppm] = 1.64 (m, 2H), 1.86 (m, 2H), 2.73 (t, 2H),3.78 (5, 2H), 8.49 (d, 1H), 8.74 (d, 1H), 2H?s obscured by solvent signal.

The synthetic route of 88625-24-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 59489-39-3 as follows. HPLC of Formula: C5H4N4

To a solution of 6-aminopyrazine-2-carbonitrile (l .Og, 8.33mmol, l .Oeq) in acetonitrile (0.5mL) was added N-Bromosuccinimide (2.22g, 12.50mmol,I .5eq). The reaction was stirred at room temperature for 12h. After completion of reaction, reaction mixture was transferred in water and extracted with ethyl acetate. Combined organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by column chromatography using 20percent ethyl acetate in hexane to obtain pure 151.1 (0.75g, 45.27percent). MS(ES): m/z 200.01 [M+H]+

According to the analysis of related databases, 59489-39-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NIMBUS LAKSHMI, INC.; GREENWOOD, Jeremy Robert; HARRIMAN, Geraldine C.; LEIT DE MORADEI, Silvana Marcel; MASSE, Craig E.; MCLEAN, Thomas H.; MONDAL, Sayan; (401 pag.)WO2018/71794; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 122-05-4,Some common heterocyclic compound, 122-05-4, name is Pyrazine-2,5-dicarboxylic acid, molecular formula is C6H4N2O4, 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.

5 mmol of (SPBOZ)2Ir(Cl)2Ir(SPBOZ)2, 25 mmol of pyrazine-2,5-dicarboxylic acid (Py2CA), and 50 mmol of potassium carbonate were mixed in 100 mL of 1,2-dichloroethane, and refluxed for 24 hours under a nitrogen atmosphere. After the reaction was complete, the solution was cooled down to about 50 C., and filtrated. The filtrated solution was purified by using column chromatography to thereby produce (SPBOZ)2Ir(Py2CA)Ir(SPBOZ)2 at a yield of 90%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Pyrazine-2,5-dicarboxylic acid, its application will become more common.

Reference:
Patent; SAMSUNG ELECTRONICS CO., LTD.,; US2008/269484; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 5521-55-1, These common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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.

Example B5Preparation of compound 6: rac-5-methyl-pyrazine-2-carboxylic acid [3-(6-amino-2,4- dimethy 1-3 -oxo -2,3,4,5 -tetrahydro -pyrazin-2-y l)-pheny 1] -amide5-Methylpyrazine-2-carboxylic acid (0.014 g, 0.104 mmol) was added to a suspension of intermediate 18 (0.021 g, 0.09 mmol) in DCM (1.5 mL) at room temperature. Then, pyridine (0.01 mL, 0.118 mmol) was added and after stirring at room temperature for 5 minutes HATU (0.038 g, 0.099 mmol) was added. The mixture was stirred at room temperature for 16 hours. The mixture was diluted with water and extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; MeOH in DCM 0/100 to 10/90). The desired fractions were collected and concentrated in vacuo. The residue was purified again by flash column chromatography (silica gel; solid injection; 7 M solution of ammonia in methanol in DCM 0/100 to 2/98). The desired fractions were collected and concentrated in vacuo to yield compound 6(0.009 g, 28% yield).

The synthetic route of 5521-55-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; TRABANCO-SUAREZ, Andres, Avelino; TRESADERN, Gary, John; MACDONALD, Gregor, James; VEGA RAMIRO, Juan, Antonio; WO2011/154374; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 109-08-0,Some common heterocyclic compound, 109-08-0, name is 2-Methylpyrazine, molecular formula is C5H6N2, 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.

2-methylpyrazine 0.478 (5 mmol) with 0.17 g of tetrabutylammonium bisulfate (0.5 mmol)5 ml of an aqueous solution of sodium hydroxide per liter was added,Heating to reflux, adding 5 mmol of p-dimethylaminobenzaldehyde,Reflux reaction. After completion of the reaction, the mixture was cooled to room temperature,The crude product was obtained by filtration and recrystallized from ethanol to give the product,Yield 56%.

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

Reference:
Patent; University of Science and Technology of China; Zhang Guoqing; Chen Biao; Xu Cheng; Wang Hao; Du Jiajun; Bi Guoqiang; Luo Yi; (111 pag.)CN107118586; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, 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. Recommanded Product: 23688-89-3

6-Chloropyrazine-2-carboxylic acid [CAS-RN: 23688-89-3] (300 mg, 1 .89 mmol,1.0 eq) was dissolved in 12 mL THF, and CDI (338 mg, 2.08 mmol, 1 eq) wasadded. Then, the reaction mixture was heated to 70C for 60 mm. On cooling, asolution of 1 -(2,2-difluoroethyl)piperazine [CAS-RN: 767609-14-3] (313 mg,2.08 mmol, 1 .03 eq) in 1 .5 mL THF was added. The reaction mixture was stirredat 70C for 2 h. The reaction mixture was partitioned between ethyl acetateand water. The water phase was extracted with ethyl acetate and the combinedorganic phases were washed with brine. The phases were separated by the useof a Whatman filter and the volatile components of the organic phase wereremoved in vacuo. Purification was conducted via preparative MPLC (Biotage Isolera; 25 g SNAP cartridge: hexane -> hexane/ethyl acetate 2/1) to give 300 mg (55% yield of theory) of the title compound.UPLC-MS (Method 1): R = 0.75 mm; MS (EI0): m/z = 292 [M+1].

The synthetic route of 6-Chloropyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 173253-42-4,Some common heterocyclic compound, 173253-42-4, name is 2-Amino-5-bromo-6-chloropyrazine, molecular formula is C4H3BrClN3, 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.

In a pressure tube were mixed 5-bromo-6-chloropyrazin-2-amine (4.32 g, 20.73 mmol), phenylboronic acid (2.78 g, 22.80 mmol, 1 .1 equiv.) and Na2003 (4.39 g, 41 .45 mmol, 2 equiv.) in a4:1 mixture of 1 ,4-dioxane : water (50 mL). The reaction mixture was sparged with argon andPd(PPh3)4 (1 .20 g, 1 .04 mmol, 5 mol%) was then added. The pressure tube was capped andthe reaction mixture was heated at 10000 overnight. After that time, the reaction mixture wascooled down to r.t., filtered and concentrated under reduced pressure. The obtained crude ma-terial was purified by flash chromatography on silica eluting with hexane: EtOAc = 1:0 – 1:1 to lead to the title product as a white solid (2.11 g, 50%). ESI-MS: 206.05 [M+H]+. 1 H NMR (300 MHz, DMSO-d6) 6 7.93 (s, 1 H), 7.66 – 7.59 (m, 2H), 7.47 – 7.32 (m, 3H), 7.00 (br s, 2H).

The synthetic route of 173253-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SELVITA S.A.; BOBOWSKA (NEE WITKOWSKA), Aneta; GALEZOWSKI, Michal; NOWAK, Mateusz; COMMANDEUR, Claude; SZEREMETA-SPISAK, Joanna; NOWOGRODZKI, Marcin; OBARA, Alicja; DZIELAK, Anna; LOZINSKA, Iwona; DUDEK (NEE SEDLAK), Marcelina; JANIGA, Anita; REUS, Jacek; WRONOWSKI, Marek; ZASTAWNA, Magdalena; RADZIMIERSKI, Adam; SWIRSKI, Mateusz; ZACHMANN, Julian; FABRITIUS, Charles-Henry; PORTER, Rod; FOGT, Joanna; (276 pag.)WO2019/2606; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem