Pyrazines

Related Products of 486424-37-7, 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. 486424-37-7 name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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.

To the 3L into the reaction bottle 50.1g II, 2L methanol. 0 – 5 C lower, to the slowly dropping 133g 98.3% concentrated sulfuric acid, then completing, heating up to 40 C, instead on invitation 48h to raw material II basic reaction end. turns on lathe does methanol, 0 – 5 C lower, adding 200 ml methanol, 500g ice water mixture, wherein the aqueous solution of sodium bicarbonate to pH=6 – 7 adds by drops full and adjusted to. Filtering, the filter cake 45 C vacuum drying 12h, get 43.2g brown solid III, yield 80.1%

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Amino-6-bromopyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; Nanjing Huawei Pharmaceutical Development Co., Ltd.; Bao Jinyuan; Huang Hui; Jiang Yuwei; Zhang Xiaoqing; (8 pag.)CN104496917; (2017); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 153800-11-4, 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. 153800-11-4 name is 2-Ethynylpyrazine, 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.

To a stirred solution of alkyne precursor 8b-16b (1.2 equiv) in THF was added dropwise a 1.0 M solution of TBAF in THF (1.44 equiv). The reaction mixture was stirred at room temperature for about 15 min. TLC analysis showed complete conversion of starting material to a major product (the de-silylation intermediate was slightly more polar than the alkyne precursor). The glycosyl azide (1.0 equiv), and 1:1 tert-butyl alcohol-water were then added to the above solution. A solution of sodium ascorbate (0.4 equiv) in water, followed by CuSO4 (0.2 equiv) in water, was successively added. The bright-yellow suspension was stirred vigorously at room temperature overnight. TLC analysis showed complete conversion of the starting material to a major product. The mixture was evaporated under reduced pressure, and the resultant residue was purified by flash chromatography to yield pure material.

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

Reference:
Article; Li, Tiehai; Guo, Lina; Zhang, Yan; Wang, Jiajia; Li, Zhonghua; Lin, Lin; Zhang, Zhenxing; Li, Lei; Lin, Jianping; Zhao, Wei; Li, Jing; Wang, Peng George; Carbohydrate Research; vol. 346; 9; (2011); p. 1083 – 1092;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 36070-80-1,Some common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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.

Dissolve 5-chloropyrazine-2-carboxylic acid (2.00 g, 12.62 mmol) in methylene chloride (30 mL) and at room temperature diisopropylethylamine (6.79 g, 39.74 mmol), 2,2,2-trifluoro Ethylamine (1.31 g, 13.24 mmol), O- (7-Azabenzotriazol-1-yl) -N, N, N ‘, N’-tetramethyluronium hexafluorophosphate (5.04 g, 13.24 mmol) is added,Stir at room temperature overnight.Saturated aqueous sodium carbonate was added, and the mixture was extracted twice with ethyl acetate and washed once with saturated brine.The extracted ethyl acetate layer was dried over anhydrous magnesium sulfate and filtered, and then ethyl acetate was evaporated under reduced pressure with an evaporator.The resulting crude product is purified by silica gel chromatography to give 5-chloro-N- (2,2,2-trifluoroethyl) pyrazine-2-Carboxamide (2.97 g, 98.9%, as a pale yellow oil) was obtained.

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

Reference:
Patent; Nippon Kayaku; Ueno, Shotaro; Hasegawa, Shinji; Atarashi, Daiju; Kobayashi, Takeshi; Miyake, Takaaki; Asano, Shou; Sumi, Takuto; (116 pag.)JP2019/94290; (2019); A;,
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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, A new synthetic method of this compound is introduced below., COA of Formula: C4H2BrClN2

Intermediate C-3 2-chloro-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazine A mixture of 2-(trifluoromethyl)pyridine-3-thiol (100 mg, 0.558 mmol), 2- bromo-5-chloro-pyrazine (195 mu, 0.670 mmol), Pd2(dba)3 (12.8 mg, 0.014 mmol), XantPhos (17.8 mg, 0.031 mmol), and DIPEA (144 mg, 1.12 mmol) in dioxane (degassed, 2.79 n L) was stirred for 2.5 h at 120 C. After cooling to RT, the reaction mixture was filtered through a pad of Celite followed by EtOAc (10 mL) wash. The combined filtrates were concentrated under reduced pressure and the resulting residue was purified by silica chromatography (0 to 25% gradient of EtO Ac/heptane) to give 2-chloro-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazine (252 mg, 0.864 mmol) as a brown oil. NMR (400 MHz, Chloroform- ) delta ppm 8.68 (dd, 7=4.7, 1.5 Hz, 1 H), 8.25 (d, 7=1.5 Hz, 1 H), 8.18 (d, 7=1.5 Hz, 1 H), 7.98 (dd, 7=8.1, 1.5 Hz, 1 H), 7.49 (dd, 7=8.0, 4.7 Hz, 1 H). MS m/z 292.0 (M+H)+.

The synthetic route of 912773-21-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; CHEN, Zhuoliang; FORTANET, Jorge Farcia; JOUK, Andriana; KARKI, Rajesh; LAMARCHE, Matthew J.; LIU, Gang; PALERMO, Mark G.; PEREZ, Lawrence Blas; SARVER, Patrick James; SHULTZ, Michael David; SENDZIK, Martin; TOURE, Bakary-Barry; YU, Bing; (173 pag.)WO2016/203406; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 120984-76-1, These common heterocyclic compound, 120984-76-1, name is 2-Bromo-3-methylpyrazine, 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.

2-Bromo-3-methylpyrazine (104 mg, 0.600 mmol),tetrakis(triphenylphosphine)palladium(0) (95%, 133 mg, 0.109 mmol) and sodium carbonate(175 mg, 1.64 mmol) were combined with 4-[3-methoxy-4-(4,4,5,5-tetramethyl-1 3,2-dioxaborolan-2-yl)phenoxy]furo[3 ,2-c]pyridine [Cl 0, which was prepared in analogous fashion to4-[3-methyl-4-(4 ,4,5,5-tetramethyl-1 ,3 ,2-dioxaborolan-2-yl)phenoxy]furo[3,2-c]pyrid me (C2) inExample 1] (200 mg, 0.545 mmol) in 1,4-dioxane (3 mL) and water (1 mL). The reaction mixturewas heated to 13000 in a microwave reactor for 1 hour. The mixture was cooled to roomtemperature, and the supernatant was decanted into another flask. The remaining solids were washed with ethyl acetate (3 x 10 mL) and the combined organic portions were concentrated in vacuo. Purification was carried out twice using silica gel chromatography (First column: Eluent:2% methanol in dichloromethane; Second column: Gradient: 0% to 100% ethyl acetate inheptane). The colorless fractions were combined and concentrated under reduced pressure to provide the product as a white solid. Yield: 85 mg, 0.25 mmol, 46%. LCMS m/z 334.0 (M+H). 1H NMR (400 MHz, CDCl3) oe 8.47 (AB quartet, downfield doublet is broadened, JAB=2.S Hz, AVAB=l4 Hz, 2H), 8.08 (d, J=5.9 Hz, 1H), 7.66 (d, J=2.3 Hz, 1H), 7.36 (d, J8.0 Hz, 1H), 7.25- 7.28 (m, 1H, assumed; partially obscured by solvent peak), 6.90-6.96 (m, 2H), 6.88 (dd, J=2.2,0.8 Hz, 1H), 3.79 (s, 3H), 2.50 (s, 3H). Yellow fractions were repurified to provide additional product: 55 mg, overall yield: 75%.

Statistics shows that 2-Bromo-3-methylpyrazine is playing an increasingly important role. we look forward to future research findings about 120984-76-1.

Reference:
Patent; PFIZER INC.; COE, Jotham, Wadsworth; ALLEN, John, Arthur; DAVOREN, Jennifer, Elizabeth; DOUNAY, Amy, Beth; EFREMOV, Ivan, Viktorovich; GRAY, David, Lawrence, Firman; GUILMETTE, Edward, Raymond; HARRIS, Anthony, Richard; HELAL, Christopher, John; HENDERSON, Jaclyn, Louise; MENTE, Scot, Richard; NASON, Deane, Milford, II; O’NEIL, Steven, Victor; SUBRAMANYAM, Chakrapani; XU, Wenjian; WO2014/72881; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-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. name: (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine

To 30 ml of degassed triflouroethanol (TFE) were added Ruthenium(II) chloride 1,5-cyclooctadiene complex (18.2 mg, 0.037 mmol) and (R )-(-)-H(S)-2- Diphenylphosphino)ferrocenyl]ethyl di-tert-butylphosphine (44.8 mg, 0.083 mmol). The solution was degassed again, and left to stir at room temperature for 1 hour. To 250 ml glass reactor were added (Z)-3-amino-l-(3-(trifluoromethyl)-5,6-dihydro- [l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-l-one (30 g, 74.07 mmol) and 100 ml TFE. The slurry was stirred and washed three times with N2. Than, the catalyst solution was added and the mixture washed three times with N2, then switched to H2 and washed three times. The H2 pressure was set to constant pressure of 5 bar and the reaction was heated to 55C for 23 hours. The TFE solution (93.3% purity and 77% R) was evaporated to yield oily-STG-base.

The synthetic route of 767340-03-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2009/70314; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 75907-74-3, A common heterocyclic compound, 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, molecular formula is C8H12N2O, 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.

Take Ligustrazine 2· 176g (16mmol) dissolved into 20ml glacial acetic acid, add 1.8ml (16mmol) of 30% hydrogen peroxide at 90 C for 4h, and then supplement 1.8ml (16mmol) 30% hydrogen peroxide to continue the reaction for 2h, TLC monitoring reaction is complete, add an appropriate amount of sodium sulfite to neutralize excess hydrogen peroxide, the reaction solution was filtered, and the filtrate was cooled at room temperature, adjust the pH at 10 with 50% sodium hydroxide, extract with dichloromethane, collect the organic layer, dehydrate the saturated brine, dry over anhydrous sodium sulfate, and recover the solvent under reduced pressure, obtained white Ligustrazine mono-nitroxide compound crude (2). The crude product is added into 1.51ml (16mmol) of acetic anhydride, heating at 105 C for 2.5 h, after TLC was monitored until the reaction has completed, it was evaporated to get dryness under reduced pressure, obtained black slurry of ligustrazine acetylate (3). The next black slurry was placed in a solution of 20 ml (THF: Me0H: H20 = 3:1:1), add 1.92g (48mmol) sodium hydroxide in batches, the reaction was stirred for 2 h, extracted with dichloromethane and organic layer was collected, dehydrated with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent is recovered under reduced pressure and then obtained a crude hydroxyl Ligustrazine, that is re-crystallized from n-hexane, obtained 1.85g of yellow needle crystals (4), the yellow crystal of TMP-0H prepared in the previous step was dissolved into 20 ml of anhydrous tetrahydrofuran, after that add 3.03 g (15.9mmol) Tscl, 2.464 g (24.4mmol) TEA, 0.15 g (12.2mmol) DMAP, stir overnight, extract with methylene chloride, dehydrate the saturated brine, dry over anhydrous sodium sulfate, filter, recover solvent, obtained light yellow chloro-Ligustrazine crude product, appropriate amount of silica gel sample, separation on silica gel column [V (petroleum ether): V (ethyl acetate) = 10:1] and then obtained colorless and transparent chloro- Ligustrazine 1.86g, yield 90.3%.

The synthetic route of 75907-74-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Lei Pengcheng; Xu Bing; Wang Penglong; (31 pag.)CN108456239; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 33332-28-4, 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. 33332-28-4 name is 2-Amino-6-chloropyrazine, 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.

Following a literature procedure (Walters, I.A.S. Tetrahedron Lett. 2006, 47, 341), a solution of dimethylzinc (2.0 M in toluene, 75.0 mL, 150.0 mmol) was carefully added in 25 mL portions to a solution of 2-amino-6-chloropyrazine (10.0 g, 77.0 mmol) and l ,3-bis(diphenylphosphino)propane-nickel (II) chloride (4.2 g, 7.8 mmol) were dry in dioxane (400 mL) under a nitrogen atmosphere. The reaction was stirred at rt for 2 h and then heated to 50 0C for 1 h and 95 0C overnight. The reaction was allowed to cool to rt and an additional charge of dimethylzinc was added (22 mL, 44 mmol) and the reaction was then maintained at 95 0C overnight. The reaction was cooled to rt, quenched over 15 min with MeOH and then concentrated to a brown solid. Water and EtOAc were added to the solid, and the mixture was sonicated. The solid was removed by filtration and brine was added to the EtO Ac-water mixture. The layers were separated, and the organic layer was dried (Na2SO^, and concentrated to give 9.72 g (~70 purity) of 6-methylpyrazin-2-amine, which was carried forward without further purification: LCMS (m/z): 110.0 (MH+), R = 0.21 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; WO2009/115572; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, 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. HPLC of Formula: C5H3ClN2O2

Preparation of (5-chloropyrazin-2-yl)(pyrrolidin-1-yl)methanone (SM-1):(SM-1 ) delta-chloropyrazine^-carboxylic acid (1 .00 gram, 6.31 mmol) in dichloromethane (30 ml_) was treated with catalytic amount of dimethylformamide, followed by (COCI)2 (0.85 ml_, 9.46 mmol). The resulting mixture was stirred over night. The reaction was concentrated and dried under vacuum to give desired delta-chloropyrazine^-carbonyl chloride as a solid (1 .05 g, 100%). delta-chloropyrazine^-carbonyl chloride (670mg, 3.79mmol) was dissolved in dichloromethane (1 OmL) and cooled to O0C. Thethylamine (1 .58ml_, 1 1 .4mmol) and pyrrolidine (0.32ml_, 3.79mmol) were then added successively drop-wise. Following the addition, the ice bath was removed and the reaction was allowed to warm to room temperature and stir for 1 hour. The reaction was then diluted with dichloromethane and washed with 1 N HCI, water, and brine. The organics were dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography eluting with 30 – 80% ethyl acetate in hexane afforded the desired (5-chloropyrazin- 2-yl)(pyrrolidin-1 -yl)methanone (SM-1 : 677.0mg, 84.5%). 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1 .86 – 1 .99 (m, 4 H),3.65 – 3.71 (m, 2 H), 3.73 – 3.79 (m, 2 H), 8.52 (d, J=1 .37 Hz, 1 H), 8.93 (d, J=1 .37 Hz, 1 H).

The synthetic route of 36070-80-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; CORBETT, Jeffrey Wayne; GUZMAN-PEREZ, Angel; PFEFFERKORN, Jeffrey Allen; TU, Meihua Mike; WO2010/103438; (2010); 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. 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, A new synthetic method of this compound is introduced below., HPLC of Formula: C5H4N4

To a suspension of 5-aminopyrazine-2-carbonitrile (414 mg, 3.44 mmol) in THF (10 mL) was added sodium hydride (230 mg, 5.73 mmol) at 0 C and the resulting mixture was then stirred at ambient temperature for 1 h. Compound 305-4 (1.0 g, 2.87 mmol) was added and stirred at 60 C for 4 h. The reaction mixture was quenched with ice water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated to afford the title compound 306-4 as a yellow solid (500 mg, 42% yield). LCMS:420.9 [M+1]. ?H NIVIR (400 1VIFIz, DMSO-d6): 2.36 (s, 3H), 3.35 (s, 3H), 3.77 (s, 3H), 5.21 (s, 2H), 5.68 (s, 1H), 6.86-6.88 (m, 2H), 8.63 (d, J 1.2 Hz, 1H), 8.86 (d, J1.2 Hz, 1H), 13.89 (s, 1H).

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; PHARMAENGINE, INC.; CAI, Xiong; QIAN, Changgeng; WANG, Yanong Daniel; (98 pag.)WO2017/132928; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem