Pyrazines

Electric Literature of 6966-01-4, A common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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 : 3-amino-6-bromopyrazine-2-carboxylic acid[00211] A mixture of methyl 3-amino-6-bromo-pyrazine-2-carboxylate (3 g, 12.93 mmol) and lithium hydroxide (1.548 g, 64.65 mmol) in MeOH (11.74 mL) and H2O (11.74 mL) was heated to 90 0C for 2 hours. The reaction mixture was allowed to cool, neutralised with HCl and diluted with water, and the resultant precipitate collected by filtration (2.2 g, 78% Yield). 1H NMR (400.0 MHz, DMSO) 7.57 (br s, 2H) and 8.39 (s, IH), 13.41 (br s, IH) ppm.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-damien; DURRANT, Steven; KAY, David; O’DONNELL, Michael; KNEGTEL, Ronald; MACCORMICK, Somhairle; PINDER, Joanne; VIRANI, Anisa; YOUNG, Stephen; BINCH, Hayley; CLEVELAND, Thomas; FANNING, Lev, T.d.; HURLEY, Dennis; JOSHI, Pramod; SHETH, Urvi; SILINA, Alina; WO2010/54398; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1196152-38-1, 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. 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a suspension of N-(3-aminobicyclo[1.1.1]pentan-1-yl)-2-(3,4- dichlorophenoxy)acetamide hydrochloride (0.08 g, 0.237 mmol, Example 2B) in N,N- dimethylformamide (0.5 mL, 6.46 mmol) was added N,N-diisopropylethylamine (0.166 mL, 0.948 mmol) followed by 2-bromo-5-(trifluoromethyl)pyrazine (0.065 g, 0.284 mmol). The reaction mixture was stirred overnight at 90 C. It was then concentrate under reduced pressure at 50 C. The residue was purified by flash column chromatography on silica gel (24 g) eluted with heptane and ethyl acetate (0 to 100%) to give 40 mg of the title compound (35.9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.78 (s, 1H), 8.59 (s, 1H), 8.44 (s, 1H), 7.99 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.27 (d, J = 2.8 Hz, 1H), 6.99 (dd, J = 9.0, 2.9 Hz, 1H), 4.51 (s, 2H), 2.37 (s, 6H). 19F NMR (376 MHz, DMSO-d6) delta ppm -64.83; MS (ESI+) m/z 447 (M+H)+.

The synthetic route of 2-Bromo-5-(trifluoromethyl)pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 768-05-8, name is Pyrazinoic acid hydrazide, 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. Computed Properties of C5H6N4O

A mixture of a solution of 0.618 g (2.5 mmol) of pyridoxal-5-phosphate 1 in 15 mL of water and a solution of 0.345 g (2.5 mmol) of pyrazine-2-carbohydrazide 2 in 15 mL of water (both solutions heated to 70-80 C) was cooled during 1 h at room temperature. The formed crystalline precipitate was filtered off, washed with small amount of cold distilled water and acetone, and dried in air. Yield 0.815 g (84.6%), light yellow crystals, Rf 0.86 (mobile phase 25% aqueous ammonia, Polygram Sil G/UV254). UV spectrum (pH = 7.4, H2O), lambdamax, nm (log epsilon): 302 (4.29); green luminescence in solid phase at lambdaex = 365 nm. 1H NMR spectrum (D2O, pD ~12), delta, ppm: 8.90 d (1H, H3, 4J = 0.9 Hz), 8.65 s (1H, CH=), 8.47 d. d (1H, H5′, 3J = 2.4, 4J = 0.9 Hz), 8.41 d (1H, H6′, 3J = 2.4 Hz), 7.51 s (1H, H6), 4.75 d (2H, CH2, 3J = 4.3 Hz), 2.22 s (3H, CH3). 13C NMR spectrum, deltaC, ppm: 166.1 (C=O),158.5 (C3), 151.2 (C2), 149.4 (C2′), 147.7 (CH=), 145.6 (C3′), 144.0 (C5′), 143.5 (C6′), 134 (C6), 130.4 (C5), 120.3 (C4), 61.7 (CH2), 18.2 (CH3). 31P NMR spectrum: deltaP 3.79 ppm. Mass spectrum, m/z: 368.07 [ M + H]+. Found, %: C 42.22; H 4.00; N 18.61. C13H14N5O6P. Calculated, %: C 42.52; H 3.84; N 19.07. M 367.25.

The synthetic route of Pyrazinoic acid hydrazide has been constantly updated, and we look forward to future research findings.

Reference:
Article; Gamov; Zavalishin; Aleksandriyskii; Sharnin; Russian Journal of General Chemistry; vol. 89; 2; (2019); p. 230 – 235; Zh. Obshch. Khim.; vol. 89; 2; (2019); p. 230 – 236,7;,
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. 1082843-72-8, name is 6-Bromo-3-chloropyrazin-2-amine, A new synthetic method of this compound is introduced below., Recommanded Product: 6-Bromo-3-chloropyrazin-2-amine

2-Bis(tert-butoxycarbonyl)amino-6-bromo-3-chloropyrazine XI 6-Bromo-3-chloropyrazin-2-amine (2000 mg, 9.59 mmol) was dissolved in DCM (48 ml) followed by triethylamine (3.99 ml, 28.78 mmol), di-tert-butyl dicarbonate (4188.12 mg, 19.19 mmol), and N,N-dimethylpyridin-4-amine (87.91 mg, 0.72 mmol). The reaction was allowed to stir at room temperature for overnight. The crude material was washed with water, dried, filtered and concentrated. The crude material was dissolved in minimal DCM and loaded onto a 25 g prepacked silica loader and eluted off a 40 g column using 0-30% MeOH/DCM. The title compound XI was isolated and identified by LCMS and NMR. The product was a mix of mono and bis boc-protected material, mainly bis boc-protected as observed by NMR.

The synthetic route of 1082843-72-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Blomgren, Peter A.; Currie, Kevin S.; Kropf, Jeffrey E.; Lee, Seung H.; Lo, Jennifer R.; Mitchell, Scott A.; Schmitt, Aaron C.; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; US2015/175616; (2015); 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. 41110-29-6, name is Methyl 3-methylpyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., name: Methyl 3-methylpyrazine-2-carboxylate

A solution of methyl 3-methylpyrazine-2- carboxylate (265A, 9.1 g, 59.8 mmol) in DCM (100 mL) was cooled to 0 C was added urea hydrogen peroxide adduct (7.8 g, 83.0 mmol), followed by dropwise addition of trifluoroacetic acid anhydride (10.8 mL, 78.0 mmol). The resulting mixture was stirred at 0 C for 1 h, and at RT for 18 h, during which LCMS indicated a mixture of two peaks corresponding to MS m/z = 169.0 [M+H]+. The reaction was diluted with DCM and quenched with saturated Na2SO3 solution; the aqueous layer was back-extracted with DCM (2 x). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (20-80% EtOAc/hexanes) afforded a mixture of two regioisomers, containing 3-(methoxycarbonyl)-2-methylpyrazine 1 -oxide and 2- (methoxycarbonyl)-3-methylpyrazine 1 -oxide (5.2 g, 30.9 mmol, 51.7% yield). The mixture of regioisomers was taken to next step without further purification. MS m/z = 169.0 [M+H]+. A solution of the mixture of 3-(methoxycarbonyl)-2-methylpyrazine 1 – oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1 -oxide (5.1 g, 15.2 mmol) in toluene (50 mL) was cooled to 0 C and phosphorus oxychloride (2.8 mL, 30.3 mmol) was added under nitrogen followed by DMF (0.12 mL, 1.52 mmol). The reaction mixture was stirred at RT for 4 h, and heated to 65 C for 18 h, cooled to RT, diluted with EtOAc and washed with saturated NaHCO3 solution. The aqueous layer was back-extracted with EtOAc (2 x). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (0-50% EtOAc/hexanes) with care afforded both isomers: methyl 5-chloro-3-methylpyrazine-2-carboxylate (265B, 0.68 g) (minor product) denoted by peak 1 and methyl 6-chloro-3-methylpyrazine-2-carboxylate (265B1, 1.50 g) (major product) denoted by peak 2. MS m/z = 187.0 [M+H]+. Peak 1 : 1H NMR (300 MHz, DMSO-d6) delta 8.73 (s, 1 H), 3.91 (s, 3H), 2.71 (s, 3H). Peak 2: 1H NMR (300 MHz, DMSO-d6) delta 8.89 (s, 1 H), 3.91 (s, 3H), 2.71 (s, 3H).

The synthetic route of 41110-29-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; AMEGADZIE, Albert; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Jian J.; CHENG, Yuan; FROHN, Michael J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul E.; LIU, Longbin; LIU, Qingyian; LOW, Jonathan D.; MA, Vu Van; MANNING, James; MINATTI, Ana Elena; NGUYEN, Thomas T.; NISHMURA, Nobuko; NORMAN, Mark H.; PETTUS, Liping H.; PICKRELL, Alexander J.; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; SIEGMUND, Aaron C.; STEC, Markian M.; WHITE, Ryan; XUE, Qiufen; (759 pag.)WO2016/22724; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 109838-85-9, 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Step B – Synthesis of Intermediate Compound Int-32c (0421) To a 500 mL flame dried flask was added (R)-2-isopropyl-3, 6-dimethoxy-2,5-dihydropyrazine (10.0 g, 54.3 mmol) and anhydrous THF (200 mL). The solution was cooled to -78 °C. n-BuLi (2.5M in hexane, 24.0 mL, 59.7 mmol) was added dropwise. After the solution was allowed to stir at -78 °C for 30 minutes, Int-32b (in 5 mL anhydrous THF) was added dropwise. After the solution was allowed to stir at -78 °C for 1 hour, it was allowed to warm up to room temperature in two hours. Water (100 mL) and Et2O (150 mL) were added. The organic layer was separated and the aqueous layer was extracted with Et2O (100 mL) twice. The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified using flash chromatography on silica gel (40 g, eluted with Et2O in Hexane: 0percent to 3percent) to provide Compound Int-32c (10.43 g, 58.0percent).

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, (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Merck Sharp & Dohme Corp.; Nair, Anilkumar Gopinadhan; Keertikar, Kerry M.; Kim, Seong Heon; Kozlowski, Joseph A.; Rosenblum, Stuart; Selyutin, Oleg B.; Wong, Michael; Yu, Wensheng; Zeng, Qingbei; EP2545060; (2015); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 21279-62-9, name is 3-Chloropyrazine-2-carboxamide, molecular formula is C5H4ClN3O, 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. category: Pyrazines

Compound 8 is prepared by reaction of 3-chlorophenylhydrazine (3 mmol) with 3- chloropyrazine-2-carboxamide (ifi, 1 mmol) in 3 mL methanol and pyridine (1 mniol). The reaction is performed in a microwave reactor at the temperature 140C, pressure 15 kPa and an output of 120 W during 30 mm. After completing the reaction, product 8 was isolated and purified by column chromatography on silica gel (mobile phase: hexane I ethyl acetate 1:1), yield 24%. Analytical data for compound 8: Dark brown crystalline solid; Mp. = 119.5- 120.9C; Elemental analysis calculated for C11H10C1N50 (m.w. 263.68): 50.10% C, 3.82% H, 26.56% N; found 50.3 1% C, 3.7 1% H, 26,55% N; IR (ATR-Ge, cm?): 3445 (-NH-), 3253 (-CONH2), 1671 (-C=O), 1598, 1522, 1476, 1413 (pyr); 1H-NMR (300 MHz, CDC13) ?HNMR (300 MHz, CDCI3) 8.34 (2H, bs, NH2), 7.92 (2H, bs, H5, H6), 7.63 – 6.82 (4H, m,1-12?, H4?, H5?, 116?), 5.71 (211, bs, NH); ?3C NMR (75 MHz, DMSO) & 168,89, 152.20,146.20, 140.24, 134.40, 132.36, 129.72, 126.57, 122.94, 120.26, 118.52; Lipophilicity: caic.values log P 0.34; experimental determined values log k = 0.5898.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 21279-62-9, its application will become more common.

Reference:
Patent; UNIVERZITA KARLOVA V PRAZE; DOLEZAL, Martin; ZITKO, Jan; JANDOUREK, Ondrej; SERVUSOVA-VANASKOVA, Barbora; (31 pag.)WO2016/95877; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5521-55-1,Some common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, molecular formula is C6H6N2O2, 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 41 2 (R)- (3-CHLORO-4-METHANESULFONYL-PHENYL)-3-CYCLOPENTYL-N- (5- [1, 3] dioxolan-2-yl- pyrazin-2-yl)-propionamide [000241] A solution of 5-methylpyrazine-2-carboxylic acid (5.0 g, 36.2 mmol), N, N-dimethylformamide dimethyl acetal (15 mL, 113 mmol) ANDN, N-DIMETHYFORMAMIDE (15 mL) was heated with stirring in an oil-bath at 90C under argon for 60 min. The temperature of the oil-bath was raised to 120C, and the heating and stirring continued for an additional 120 min. The reaction mixture was then cooled to 25C and concentrated in vacuo to a volume of about 10 mL. The oily residue was partitioned with water (50 mL) and ethyl acetate (50 mL). The aqueous phase was further extracted with ethyl acetate (2 x 50 mL), and each organic extract was washed with a portion of a saturated aqueous sodium chloride solution (25 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to a dark oil. The residue was treated with a solution of diethyl ether/hexanes (50 mL, 3: 2) to produce an orange solid. The solid was collected by filtration and washed with a mixture of diethyl ether/hexanes (25 mL, 1: 1) to afford 5- (2-DIMETHYLAMINO-VINYL)-PYRAZINE-2-CARBOXYLIC acid methyl ester (4.94 g, 66 %) as a bright orange solid.

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2004/52869; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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: 113305-94-5

2-Amino-5-cyano pyrazine (0.25 g, 2.08 mmol) was dissolved in a mixture of 3:1 THF and DCM (40 mL) and pyridine (0.49 g, 6.2 mmol) was added. The mixture was stirred for 15 minutes then phenylchloroformate (0.97 g, 6.2 mmol) was added and the reaction mixture was heated at 50C for 2 hours. The reaction mixture was allowed to cool to room temperature then DCM (40 mL) and water (25 mL) were added. The separated organic layer was washed with water (2 x 25 mL), brine (25 mL), dried (Na2S0 ) and the solvents removed under reduced pressure to give the title compound (0.8 g) which was used without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 113305-94-5, its application will become more common.

Reference:
Patent; SENTINEL ONCOLOGY LIMITED; BOYLE, Robert George; BOYCE, Richard Justin; WO2013/72502; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 55557-52-3, A common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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: Compounds 5-10 (Supplemental Figure 6A, Scheme 1), 12-15 (Supplemental Figure 6B, Scheme 2), and 17, 18 (Supplemental Figure 6C, Scheme 3) were prepared by a modified procedure as reported by Kayser F. et al. (ref 1) and Chen Z. et al. (ref. 2). To a solution of the corresponding thiol, or phenol 4 (0.85 g, 5.0 mmol) in 15 ml DMF (N, N-Dimethylformamide) 3-chloropyrazine-2-carbonitrile (0.66 g, 4.76 mmol) and Na2CO3 (1.01 g, 9.52 mmol), or substituted chrolopyridines, or chlorobenzenes, were added respectively and the resulting mixture was refluxed at 80 C for 12 h. The DMF was evaporated at reduced pressure and the compound A residue was recrystallized from ethyl acetate. The rest of the compounds were purified by flash chromatography on silica gel with ethyl acetate:hexanes (5-100% gradient).

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:
Article; Freeman, Lita A.; Demosky, Stephen J.; Konaklieva, Monika; Kuskovsky, Rostislav; Aponte, Angel; Ossoli, Alice F.; Gordon, Scott M.; Koby, Ross F.; Manthei, Kelly A.; Shen, Min; Vaisman, Boris L.; Shamburek, Robert D.; Jadhav, Ajit; Calabresi, Laura; Gucek, Marjan; Tesmer, John J. G.; Levine, Rodney L.; Remaley, Alan T.; Journal of Pharmacology and Experimental Therapeutics; vol. 362; 2; (2017); p. 306 – 318;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem