Category: Pyrazines

These common heterocyclic compound, 2423-65-6, name is Pyrazine 1-oxide, 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. name: Pyrazine 1-oxide

General Procedure 2:; Palladium-Catalyzed Direct Arylation with Aryl Chlorides and Bromides.; To a dried flask was added the diazine N-oxide (1.0 to 3.0 equiv.), K2CO3 (2.0 equiv.), Pd(OAc)2 (5 mol %) and HP(t-Bu)3BF4 (15 mol %). If the arylhalide is a solid, it is added at this point (1.0 equiv.). The flask and its contents were then purged under nitrogen for 10 minutes. If the aryl halide is a liquid, it is added via syringe after purging, followed by the addition of degassed dioxane (to produce a reaction concentration of 0.3 M relative to the halide). The reaction mixture was then heated at 110 C. until the reaction was complete, after which the volatiles were removed under reduced pressure and the residue was purified via silica gel column chromatography.; 2-p-Tolylpyrazine N-oxide (81) Synthesised according to general procedure 2 employing the corresponding aryl bromide and chloride or 60 with the corresponding aryl iodide. Purification via silica gel column chromatography using 100% DCM then a mixture of 20% Acetone/DCM gave a white solid, 72% (from the bromide), 75% (from the chloride) and 77% (from the iodide). 1H NMR (300 MHz, CDCl3, 293K, TMS): delta 8.63 (1H, s), 8.37 (1H, s), 8.20 (1H, s), 7.72 (2H, d, J=8.1 Hz), 7.33 (2H, d, J=7.8 Hz), 2.43 (3H, s). 13C NMR (75 MHz, CDCl3, 293K, TMS): 148.2, 145.2, 144.6, 140.8, 134.2, 129.8, 129.0, 125.9, 21.5.

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

Reference:
Patent; University of Ottawa; US2008/132698; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 121246-96-6, name is 3-Chloropyrazine-2-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 3-Chloropyrazine-2-carbaldehyde

PREPARATION 14; EPO 4-Methyl-3,4,5,6-tetrahvdro-2H-?,2’lbipyrazinyl-3′-carbaldehvde;.S-Chloro-pyrazine^-carb-aldehyde (Turck, et al., Synthesis 1988, 881-4) (6.01 g, -40 mmol), N-methylpiperazine (6.6 mL, 59.4 mmol) and K2CO3 (8.3g, 60.0 mmol) were refluxed for 1h in dioxane (250 mL). After cooling, the mixture was filtered and concentrated to an orange oil. This was dissolved in EtOAc (500 mL) and washed with water (4×150 mL) and brine, dried (MgSO4) and concentrated. Chromatography with 5% MeOH/ CH2CI2 gave 3.34 g (40%) of PP14 as a dark red oil : NMR (CDCI3) 9.94 (s, 1 H), 8.18 (d, J= 2.1 Hz, 1 H), 8.08 (d, J = 2.1 Hz, 1 H), 3.59 (t, J= 5.2 Hz, 4H), 2.53 (t, J = 5.0 Hz, 4H), 2.32 (s, 3H).

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 121246-96-6.

Reference:
Patent; PFIZER PRODUCTS INC.; WO2006/48727; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1174321-06-2, 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. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

N,N-Dimethylformamide (2 mL), triethylamine (0.081 mL, 0.58 mmol) and 1- [bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (48 mg, 0.126 mmol, HATU) were added to a mixture of the product of Example 197B (40 mg, 0.097 mmol) and 5-(difluoromethyl)pyrazine-2-carboxylic acid (Manchester, 16.9 mg, 0.097 mmol) in sequential order. The reaction mixture was then stirred at ambient temperature for 0.5 hour. The resulting solution was filtered through a glass microfiber frit and purified by preparative HPLC [Waters XBridge C185 mum OBD column, 30 ¡Á 100 mm, flow rate 40 mL/minute, 5-100% gradient of acetonitrile in buffer (0.025 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to give the title compound (39 mg, 0.086 mmol, 88% yield). 1H NMR (500 MHz, DMSO-d6) delta ppm 9.34 (s, 1H), 9.31- 9.22 (m, 1H), 8.99 (s, 1H), 8.53 (s, 1H), 7.50 (t, J = 8.9 Hz, 1H), 7.21 (t, J = 54.0 Hz, 1H), 7.08 (dd, J = 11.4, 2.8 Hz, 1H), 6.86 (ddd, J = 9.0, 3.0, 1.1 Hz, 1H), 4.49 (s, 2H), 2.18 – 2.12 (m, 2H), 1.99- 1.80 (m, 6H); MS (ESI+) m/z 455 (M+H)+.

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, 5-(Difluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

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

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. 681249-57-0, name is 2-(Trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-(Trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyrazine

To a slurry of (3-(4-(4-(bromomethyl)benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (200 mg, 0.451 mmol)) and 2-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine (95 mg, 0.496 mmol) in dry MeCN (5 mL, 96 mmol), was added DIEA (0.197 mL, 1.128 mmol) and the resulting white suspension was stirred at room temperature for 2 h and heat to 40 C. for 4 additional hours The mixture was cooled at 0 C. The suspension was filtered. The solid was washed with water (~50 mL) and dried in vacuum oven at 50 C. to give 3-(1-oxo-4-((4-((2-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)methyl)benzyl)oxy)isoindolin-2-yl)piperidine-2,6-dione as a white solid (135 mg, 54% yield): HPLC: Waters Symmetry C18, 5 mum, 3.9*150 mm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 6.33 min (98.2%); mp: 139-142 C.; 1H NMR (DMSO-d6) delta 1.89-2.05 (m, 1H, CHH), 2.34-2.48 (m, 1H, CHH), 2.57 (d, J=19.1 Hz, 1H, CHH), 2.82-2.98 (m, 1H, CHH), 3.02 (t, J=5.5 Hz, 2H, CH2), 3.80 (s, 2H, CH2), 3.82 (s, 2H, CH2), 4.20-4.31 (m, 3H, CHH, CH2), 4.42 (d, J=17.6 Hz, 1H, CHH), 5.11 (dd, J=5.1, 13.2 Hz, 1H, CH), 5.25 (s, 2H, CH2), 7.30-7.36 (m, 2H, Ar), 7.38-7.44 (m, 2H, Ar), 7.45-7.54 (m, 3H, Ar), 10.96 (s, 1H, NH); 13C NMR (DMSO-d6) delta 22.34, 31.16, 45.07, 46.54, 47.73, 49.17, 51.56, 59.42, 69.35, 114.99, 115.23, 127.80, 128.92, 129.80, 129.95, 133.30, 135.73, 137.05, 152.82, 153.46, 167.97, 170.95, 172.80; Two carbon signals are not observed (probably due to splitting of CF3, and CCF3); LCMS: MH=555; Anal Calcd for C27H25F3N6O4+0.5 H2O: C, 57.55; H, 4.65; N, 14.91; F, 10.11; Found: C, 57.42; H, 4.32; N, 14.60; F, 9.92.

According to the analysis of related databases, 681249-57-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Man, Hon-Wah; Muller, George W.; Ruchelman, Alexander L.; Khalil, Ehab M.; Chen, Roger Shen-Chu; Zhang, Weihong; US2011/196150; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 54013-04-6, name is Ethyl 5-chloropyrazine-2-carboxylate, 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 54013-04-6, category: Pyrazines

Ethyl 5-chloro-2-pyrazinecarboxylate (1.74 mmol) was added hydrazine monohydrate (1 mL) and heated 100 C for1 h. Then ethanol was added (10 mL), the mixture was refluxed for 3 h, finally filtered and washed with ethanol[19]. Brown crystals from ethanol. lambda max. (EtOH) (nm) (logepsilon): 203 (4.69), 279 (5.21), 327 (4.79); IR max.(cm-1): 3327,3277, 3100, 1627, 1568, 1537, 1496, 1197, 1116, 889, 696; 1H-NMR (300 MHz), (DMSO-d6/TMS) ppm: 4.42 (d, 2H,NH2), 8.45 (s, 1H, pyrazine H6 ), 8.61 (s, 1H, pyrazine H3),9.41 (s, 1H, NH). Anal. Cal. for C5H5ClN4O (M.W.: 172.572g/mol): C, 34.80; H, 2.92; N, 32.47. Found: C, 34.60; H,2.90; N, 32.00

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, Ethyl 5-chloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Kocyigit-Kaymakcioglu, Bedia; Yazici, Senem Sinem; Tok, Fatih; Dikmen, Miri?; Enguer, Selin; Oruc-Emre, Emine Elcin; Iyidogan, Aysegul; Letters in drug design and discovery; vol. 16; 5; (2019); p. 522 – 532;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4774-14-5,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.

Example B-10: Preparation of (2S)-1-(4-(1-isopropyl-3-(5-methyl-5H-pyrrolo[3,2-b]pyrazin-2-yl)-1H- pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-10) cr Et3NB-10-1 B-10-2 B-10-3Preparation of 6-chloropyrazin-2-amine (B-10-2). B-10-1 B-10-2A mixture of 2,6-dichloropyrazine (300 g, 2 mol) and 28% aq. NH3 (8 L) was stirred at 14O0C in a sealed system for 14 hours. TLC (petroleum ether/EtOAc 3:1 ) indicated complete consumption of starting material. The reaction mixture was extracted with EtOAc (3 L x 3). The combined organic layers were washed with saturated aqueous NaCI (3 L), dried over Na2SO4 and concentrated in vacuo to give crude compound B-10-2, which was purified by column chromatography (silica gel, petroleum ether/EtOAc 2:1) to yield pure compound B-10-2 (410 g, yield: 59.7%) as a white solid.

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; WO2009/16460; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 113305-94-5, 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.

5-chloro-3- (cyclohex-1-en-1-yl) -7-methoxy-6- (4-methoxyphenyl) -2-phenylpyrazolo [1, 5-a] pyrimidine (500 mg, 1.07 mmol) , 5-aminopyrazine-2-carbonitrile (257 mg, 2.15 mmol) , palladium (II) acetate (48 mg, 0.214 mmol) , xantphos (124 mg, 0.214 mmol) and sodium carbonate (230 mg, 0.215 mmol) in 1, 4-dioxane (10 mL) under heating at 110 for 4 hours under nitrogen atmosphere. LC-MS: m/z 530.2 (M+H) +.

The synthetic route of 5-Aminopyrazine-2-carbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AGIOS PHARMACEUTICALS, INC.; TRAVINS, Jeremy, M.; KONTEATIS, Zenon, D.; SUI, Zhihua; YE, Zhixiong; (199 pag.)WO2018/39972; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 33332-28-4, 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 33332-28-4 as follows.

A solution of 2-amino-6-chloropyrazine (25 g, 193.1 mmol) in MeOH (500 mL) was treated with NBS (34.3 g, 193.1 mmol), portion-wise, over 1 hour. The resulting mixture was stirred for 16 hours thereafter. TLC analysis at this time shows a small amount of starting material remaining. Another 1.4 g NBS added and reaction heated to 50¡ã C. for 2 hours. The mixture was then cooled to 38¡ã C. and treated with NCS (25.8 g, 193.1 mmol). The reaction mixture was heated to 50¡ã C. for 16 hours thereafter. The mixture was then cooled to room temperature and treated with water (500 mL). The precipitate was collected by filtration and dried in a vacuum desiccator to afford 45.4 g (97percent yield) of 2-amino-5-bromo-3,6-dichloropyrazine as a white solid: 13C NMR (75 MHz, CDCl3) delta 149.9 (s), 145.6 (s), 129.6 (s), 121.5 (s). LCMS (15-95percent gradient acetonitrile in 0.1percent TFA over 10 min), single peak retention time=4.51 min on 30 mm column, (M+H)+=244, (M+H+ACN)+=285.

According to the analysis of related databases, 33332-28-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MediBeacon Inc.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (52 pag.)US2019/125902; (2019); 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. 6270-63-9, name is Pyrazin-2(1H)-one, A new synthetic method of this compound is introduced below., Quality Control of Pyrazin-2(1H)-one

To a solution of methyl 5-( I -bromo-3-cyclopropylpropyl)-2-fluorophenylcarbamate(258c) (0.925 g, 2.80 rnmol) in DMF (10 mL) was added pyrazin-2(LH)-one (0.323 g, 3.36mmol) cesium carbonate (0.867 g, 2.66 mmol) and stirred at room temperature overnight. The reaction mixture was diluted with water (50 mL), extracted with ethyl acetate (2 x 75 rnL), combined organics were dried over anhydrous MgSO4, filtered and evaporated to dryness. The residue was purified by flash column chromatography [silica gel 24 g, elutingwith ethyl acetate/methanol (9: 1) in hexanes from 0-75%] to furnish methyl 5-(3-cyc lopropyl- 1 -(2-oxopyrazin- 1(2 H)-yl)propyl)-2-fl uorophenylcarbamate (259a) (0.304 g, 31 % yield) as a colorless wax. MS (ES+): 368.3 (M+Na), MS (ES-) 344.2 (M-l).

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; BIOCRYST PHARMACEUTICALS, INC.; KOTIAN, Pravin, L.; BABU, Yarlagadda, S.; WU, Minwan; CHINTAREDDY, Venkat, R.; KUMAR, V., Satish; ZHANG, Weihe; WO2015/134998; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 63744-22-9, A common heterocyclic compound, 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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 1. Preparation of [4-(6-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone A solution of 6,8-dibromoimidazo[1,2-a]pyrazine (500 mg, 1.8 mmol), (4-aminophenyl)(morpholino)-methanone (408 mg, 1.98 mmol) and CSA (356 mg, 1.53 mmol) in iPrOH (30 mL) was stirred at 90 C. overnight. The solvent was evaporated. The residue was dissolved in DCM (30 mL). A NaHCO3 solution (10 mL) was added to adjust to pH=8. The organic layer was separated and dried over Na2SO4. The drying agent was removed by filtration and the resultant solution was concentrated in vacuo. The residue was purified through a silica-gel column (ethyl acetate:petroleum ether=1:1) to give the desired product as a yellow solid (500 mg, 69% yield). LC-MS: 404 [M+1]+, tR=1.409 min.

The synthetic route of 63744-22-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoffmann-La Roche Inc.; Brotherton-Pleiss, Christine E.; Lopez-Tapia, Francisco Javier; Lou, Yan; US2013/150360; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem