Category: Pyrazines

Reference of 912773-24-1, These common heterocyclic compound, 912773-24-1, name is 6-Bromoimidazo[1,2-a]pyrazine, 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 : To a solution of 6-bromoimidazo[l,2-a]pyrimidine (2.4 g, 12.1 mmol) in DMF, were sequentially added (4-methylpiperazin-r-yl)(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)methanone (80% of 4.1 g, 12.1 mmol), a solution of NaHC03 (3.1g, 36.3 mmol) in water (30 mL), water (3 mL) and (A-Phos)2PdCl2 (400 mg, 0.60 mmol). The reaction mixture was heated at 90 C for 4 h, then was diluted with water (100 mL) and extracted with EtOAc (3><100 mL). The combined organic layer was dried over Na2S04, filtered and concentrated under reduced pressure.. The residue was purified by flash column chromatography (silica gel, eluent CHCl3/MeOH 95 :5 to 85 : 15) to afford of (4-(imidazo[ 1 ,2-a]pyrazin-6-yl)phenyl)(4- methylpiperazin-l-yl)methanone (1.5 g, 65%). 1H NMR (400 MHz, CDC13) delta 8.60 (d, J~ 2,0 Hz, 1 H), 8.10 (d, J= 4.0, 1 H), 7.80 (d, J= 8.0 Hz, 1 H), 7.58 (m, 4 H) 7.39 (d, J= 8.0, 1 H), 3.84 (br s, 2 H), 3.50 (br s, 2 H), 2.40 (br s, 4 H), 2.35 (s, 3 H); MS (ESI) m/z 322 [M+1] Statistics shows that 6-Bromoimidazo[1,2-a]pyrazine is playing an increasingly important role. we look forward to future research findings about 912773-24-1. Reference:
Patent; AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH; NACRO, Kassoum; DURAISWAMY, Athisayamani, Jeyaraj; CHENNAMANENI, Lohitha, Rao; WO2013/147711; (2013); 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 4858-85-9 as follows. Formula: C4H2Cl2N2

A mixture 2,3-dichloropyrazine (50 g, 0.34 mmol) and concentrated aqueous ammonium hydroxide (200 mL) was stirred at 85 C. in a closed pressure vessel for 4 days. The mixture was cooled to 25 C., water (200 mL) was added, and the mixture was filtered. The solid was washed with water (400 mL), then with dichloromethane (400 mL) and dried under vacuum. Compound 100 was isolated as a white solid 32.5 g (73%). 1H NMR (400 MHz, DMSO-d6 delta 7.93 (d, 1H), 7.55 (d, 1H), 6.79 (bs, 2H).

According to the analysis of related databases, 4858-85-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Schering Corporation; US2007/105864; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 875781-43-4,Some common heterocyclic compound, 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, molecular formula is C6H4BrN3, 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.

[0358] Step 1. To a suspension of 15A (1.0 equiv.) in THF (0.15 M) is added a solution of 2.0 M aqueous NaOH (3 equiv.). The homogeneous reaction mixture is stirred overnight, and then the organics are removed under reduced pressure. The aqueous residue is brought to pH–4 with 1.0 M aqueous HC1. The resulting precipitate is collected by filtration and rinsed with H20 to afford a solid of 1 5B. The filtrate is extracted with EtOAc (2x), and the organics are concentrated under reduced pressure to provide an additional portion of 15B.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, its application will become more common.

Reference:
Patent; TP THERAPEUTICS, INC.; CUI, Jingrong Jean; LI, Yishan; ROGERS, Evan W.; ZHAI, Dayong; WO2015/112806; (2015); A3;,
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. 6294-70-8, name is 5,6-Dimethylpyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 6294-70-8

To an acetonitrile solution (8.00 mL) of the compound (519 mg) obtained in Reference Example 433 was added N-bromosuccinimide (749 mg) at 0C, and the reaction mixture was stirred at room temperature for 30 min. Aqueous sodium thiosulfate solution was added and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and the obtained residue was purified by silica gel column chromatography (solvent; hexane/ethyl acetate=100/0 – 60/40) to give the title compound (619 mg). MS(ESI)m/z; 202,204[M+H]+

According to the analysis of related databases, 6294-70-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; OKUYAMA, Masahiro; FUKUNAGA, Kenji; USUI, Kenji; HAYASHI, Norimitsu; IIJIMA, Daisuke; HORIUCHI, Hideki; FUJIMOTO, Nobuaki; (218 pag.)EP3372601; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1458-01-1, name is Methyl 3,5-diamino-6-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 1458-01-1, name: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate

General procedure: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Article; Buckley, Benjamin J.; Majed, Hiwa; Aboelela, Ashraf; Minaei, Elahe; Jiang, Longguang; Fildes, Karen; Cheung, Chen-Yi; Johnson, Darren; Bachovchin, Daniel; Cook, Gregory M.; Huang, Mingdong; Ranson, Marie; Kelso, Michael J.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 24; (2019);,
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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C9H16N2O2

The chiral auxiliary group (2.12 g, 11.5 mmol) was dissolved in dry THF solution (10 mL) and cooled to -78 o.n-Butyllithium reagent (2.5 M in hexane, 5.5 mL,13.8 mmol) was added dropwise to the reaction system and reacted at -78 °C for 30 minutes.Add the substrate (3.24 g, 12.1 mmol) in dry THF (10 mL).-78 oC reaction for 60 minutes. After the reaction system is quenched with saturated brine,Take it out from the -78 oC environment and naturally rise to room temperature.It was then extracted 3 times with ethyl acetate (30 mL x 3). Combine the organic phase,Backwash twice with saturated brine (50 mL x 2), dry over anhydrous magnesium sulfate.Filter and concentrate. Obtaining crude product by column chromatography for separation and purification(ethyl acetate: n-hexane = 1: 6), the product was obtained as a pale yellow solid.The yield is 3.85 g,Yield 70percent,

According to the analysis of related databases, 109838-85-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Wang Lu; (17 pag.)CN109384806; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, 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. Computed Properties of C6H8ClF3N4

Example 2: Preparation of benzyl (R)-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-alpha]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)-4-oxobutan-2-ylcarbamate (Compound of formula 2 wherein R is Cbz) [39] (R)-3-Cbz-amino-4-(2,4,5-trifluorophenyl)-butanoic acid (3.0g, 8.2mmol) and tetrahydrofuran (THF, 30ml) were charged and dissolved in a dry flask, and N-methylmorpholine (2.7ml, 24.5mmol) was added thereto. Then, the mixture was cooled to a temperature of 0 to 5C, and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.86g, 10.6mmol) was added thereto. After being stirred at a temperature of 0 to 5C for one hour, 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-alpha]pyrzine hydrochloride (2.05g, 9.0mmol) was added and the reaction mixture was stirred while warming to room temperature (20 to 25C). After the completion of the reaction was confirmed by TLC, the reaction liquid was cooled to 10C, and dichloromethane (30.0ml) and water (30.0ml) were added thereto, followed by separation of layers. The organic layer was washed with saturated sodium bicarbonate (30.0ml) and saline (30.0ml), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then crystallized from ethyl acetate (12.0ml) and isopropyl alcohol (6.0ml) to afford 3.98g (yield: 90%) of benzyl-(R)-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]-triazolo[4,3-alpha]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)-4-oxobutan-2-ylcarbamate.[40] 1H NMR delta7.10-7.34(m, 5H), 7.04(dd, 1H, J=0.012), 6.84(dd, 1H, J=0.013), 5.01(s, 2H), 4.90(NH), 4.20(s, 2H), 4.10(t, 2H), 4.04(t, 2H), 3.97(m, 1H), 2.97(t, 2H), 2.70(t, 2H)

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ST PHARM CO., LTD.; LIM, Geun Gho; CHANG, Sun Ki; BYEON, Chang Ho; WO2012/99381; (2012); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 710322-57-9,Some common heterocyclic compound, 710322-57-9, name is Methyl 5-formylpyrazine-2-carboxylate, molecular formula is C7H6N2O3, 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.

A mixture of 5-formyl-pyrazine-2-carboxylic acid methyl ester (0.400 g, 2.40 mmol), piperidine (0.204 g, 2.40 mmol), and NaB(OAc)3H (1.40 g, 3.60 mmol) in DCM (10 mL) was stirred for 18 h at rt. The reaction was quenched by the addition of 10% aq. NaOH (10 mL) and the mixture was stirred for 30 min. The mixture was extracted with DCM (3*20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to yield the title compound (0.130 g, 23%).

The synthetic route of 710322-57-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Carruthers, Nicholas I.; Shah, Chandravadan R.; Swanson, Devin M.; US2005/222151; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 21279-62-9, 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 21279-62-9 as follows.

General procedure: Compounds 1-6 were prepared according to conventional organic synthesis methods. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was dissolved in THF (20 mL) in a round bottom flask and after that treated with two equivalents of the corresponding benzylamine and an equimolar amount of triethylamine. The reaction was conducted with continuous stirring and heating (70 C) under reflux in an oil bath for 15 h. Compounds 7-15 were synthesised using a microwave reactor with a focused field. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was put into a thick-walled tube together with the corresponding benzylamine (2.54 mmol), pyridine (1.27 mmol), methanol (approx. 5 mL) and a magnetic stir bar and then sealed with a special cap. The reaction parameters were set according to the previously published paper as follows-140 C, 30 min, 200 W [29]. Reaction progress was checked by TLC (hexane:ethyl acetate-1:1). Regardless of the synthesis method used,all reaction mixtures were adsorbed on silica and subjected to preparative flash chromatography (hexane and ethyl acetate, gradient elution, detection wavelengths 260 nm and 280 nm). Products were recrystallized from ethanol or ethanol and water if necessary. All final substances were chemically characterized (1H-NMR, 13C-NMR, IR, melting point and elemental analysis).

According to the analysis of related databases, 21279-62-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Jandourek, Ondrej; Tauchman, Marek; Paterova, Pavla; Konecna, Klara; Navratilova, Lucie; Kubicek, Vladimir; Holas, Ondrej; Zitko, Jan; Dolezal, Martin; Molecules; vol. 22; 2; (2017);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 13535-07-4, 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 13535-07-4 as follows.

To a solution of (4S)-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3- b][l,4]diazepine (600 mg, 2.378 mmol), triphosgene (706 mg, 2.378 mmol) and triethylamine (1.989 mL, 14.27 mmol) in tetrahydrofuran (THF) (15 mL) stirred under nitrogen at room temperature for 30 min was added 5-ethylpyrazin-2-amine (879 mg, 7.13 mmol). The reaction mixture was stirred at 70 C for 16 h and cooled to room temperature and then the reaction mixture was poured in to water and extracted with EtOAc (3 X 15 mL). The combined organic layers were washed with water, brine solution, dried over sodium sulfate and evaporated to give crude compound (TLC eluent: 5% MeOH in DCM: RrO. l; UV active). The crude compound was purified by column chromatography using Neutral Alumina and eluted with 30%EtO Ac/Pet ether to afford pure (4S)-N-(5- ethylpyrazin-2-yl)-7-(6-methylpyridin-3-yl)-3,4-dihydro-l,4-methanopyrido[2,3- b][l,4]diazepine-5(2H)-carboxamide (383 mg, 0.953 mmol, 40.1 % yield), LCMS (m/z): 402.3 [M+H]+.1H NMR (400 MHz, CDC13): delta ppm 13.65 (s, 1 H) 9.41 (d, J=1.53 Hz, 1 H) 9.11 (d, J=2.19 Hz, 1 H) 8.41 (dd, J=8.22, 2.52 Hz, 1 H) 8.22 (d, J=1.32 Hz, 1 H) 7.61 (d, J=7.89 Hz, 1 H) 7.40 (d, J=8.11 Hz, 1 H) 7.32 (d, J=8.11 Hz, 1 H) 5.70 (dd, J=6.03, 3.18 Hz, 1 H) 3.34 – 3.13 (m, 3 H) 3.02 (dd, J=12.06, 3.29 Hz, 1 H) 2.83 (q, J=7.53 Hz, 2 H) 2.64 (s, 3H) 2.40-2.34 (m, 1 H) 2.15 – 2.03 (m, 1 H) 1.33 (t, J=7.56 Hz, 3 H).

According to the analysis of related databases, 13535-07-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; ELLIS, James Lamond; EVANS, Karen Anderson; FOX, Ryan Michael; MILLER, William Henry; SEEFELD, Mark Andrew; (766 pag.)WO2016/79709; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem