Category: Pyrazines

Synthetic Route of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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-7: 6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid methyl esterStep 1: 3-amino-6-cyclopropylpyrazine-2-carboxylic acid methyl esterTo a suspension of 3-amino-6-bromopyrazine-2-carboxylic acid methyl ester (17.8 g, 76.7 mmol), cyclopropylboronic acid (8.57 g, 99.7 mmol), potassium phosphate (57.0 g, 268 mmol) and tricyclohexylphosphine (2.15 g, 7.67 mmol) in toluene (445 ml) and water (22 ml) was added palladium(II) acetate (0.86 g, 3.84 mmol). The reaction mixture was heated to 100 C. and stirred for 20 h. Water (200 ml) was added, the organic layer was washed with water and brine and the aqueous layer was back-extracted with ethyl acetate. The combined organic phases were dried and the solvent was evaporated. The product was obtained after silica gel chromatography using a heptane/ethyl acetate gradient as yellow solid (1.69 g, 11.4%).MS: M=194.1 (M+H)+

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-bromopyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; Bleicher, Konrad; Flohr, Alexander; Zbinden, Katrin Groebke; Koerner, Matthias; Kuhn, Bernd; Peters, Jens-Uwe; Rodriguez-Sarmiento, Rosa Maria; Vieira, Eric; US2011/183979; (2011); 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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 16298-03-6

A solution of methyl 3-aminopyrazine-2-carboxylate (3.0 g, 19.6 mmol) and BS (3.5 g, 23.5 mol) in MeCN (70 mL) was stirred at 70°C for 5 h. Then the mixture was concentrated and extracted with EtOAc. The organic layer was washed with a2S03 (a.q.) and brine, dried over Na2S04 and concentrated in vacuo. The crude product of methyl 3-amino-6- bromopyrazine-2-carboxylate (3.0 g, yield: 92percent) was used for next step without further purification. -NMR (CDC13, 400 MHz) delta 8.18 (s, 1H), 6.54-6.93 (m, 2H), 3.86 (s, 3H). MS (M+H)+: 232 / 234.

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 16298-03-6.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DAI, Xing; LIU, Hong; PALANI, Anandan; HE, Shuwen; NARGUND, Ravi; XIAO, Dong; ZORN, Nicolas; DANG, Qun; MCCOMAS, Casey, C.; PENG, Xuanjia; LI, Peng; SOLL, Richard; WO2014/209727; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1062608-42-7, name is 5-Bromo-3-iodopyrazin-2-amine, molecular formula is C4H3BrIN3, 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. Safety of 5-Bromo-3-iodopyrazin-2-amine

To the solution of compound (iii) (355 mg, 1.18 mmol) in 1,4-dioxane (5 ml) was added a boronic acid of formula (iv) such as 6-methoxypyridin-3-yl boronic acid (CombiB locks 190 mg, 1.24 mmol) at RT and the reaction mixture was purged with N2 gas for 30 minutes. Bis(triphenylphosphine)palladium(II)chloride (58 mg, 0.08 mmol) and 1 M aqueous solution of potassium carbonate (1.42 ml, pre-purged with N2 gas) were added to the reaction mixture. The solution was heated to reflux for 16 h and then cooled to RT, added Brine solution (5 ml) and extracted with ethyl acetate (10 ml X 4). Combined organic layers were dried over anhydrous Na2S04 and concentrated. Crude material was purified by column chromatography over silica gel 230-400 mesh by using 1-2% MeOH in DCM as an eluent to yield compound (v) (150 mg, 45.18%) as solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1062608-42-7, its application will become more common.

Reference:
Patent; UNIVERSITY OF CAPE TOWN; MMV MEDICINES FOR MALARIA VENTURE; YOUNIS, Yassir; CHIBALE, Kelly; WITTY, Michael, John; WATERSON, David; WO2013/121387; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 59489-71-3, 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. 59489-71-3, name is 2-Amino-5-bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows.

2-amino-5-bromopyrazine (5.25g, 30mmol,1 eq.) and phenyl- boronic acid (5.5 g, 45mmol, 1.5 eq.) were dissolved in toluene (100 mL) and stirred at room temperature. Ethanol (20 mL) and 1 M Na2CO3 aq. (48 mL) were added to the reaction mixture. After vacuum deaeration and argon gas protection, bis-(triphenylphosphine) palladium(II) chloride (300 mg, 0.43 mmol, 5.5% of 2-amino-5-bromopyrazine) in 10 mL of toluene was added to the solution and the mixture was deaerated again and stirred for 2 hours at 105 C under argon atmosphere. After cooling to room temperature, the solution was filtered through a diatomite pad to remove the palladium catalyst. The solution was extracted with ethyl acetate, and the brown organic phase was washed with water and brine, dried over Na2SO4 and evaporated.The resulting residue was purified by silica gel column chromatography using petroleum ether/ethyl acetate 1/1, v/v , affording 2-amino-5-phenylpyrazine (7) as a yellow solid (4.8g, 92.8%).1HNMR (DMSO-d6, 300 MHz): delta8.50 (s, 1H), 7.97 (s, 1H), 7.90 (d, 2H,J=7.8Hz), 7.44-7.39 (t, 2H), 7.32-7.28 (t, 1H), 6.55 (s,2H); ESI-MS calcd. for C10H9N3: 171.1, found: 173.2 (M+2H+).

The chemical industry reduces the impact on the environment during synthesis 2-Amino-5-bromopyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Article; Yuan, Ming-Liang; Jiang, Tian-Yu; Du, Lu-Pei; Li, Min-Yong; Chinese Chemical Letters; vol. 27; 4; (2016); p. 550 – 554;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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. Formula: C4H5N3

Imidazo[1,2-aJpyrazine: A solution of aminopyrazine (1 g, 10.5 mmol) and chloroacetaldehyde (50% wt in H,O; 1.98 g, 12.6 mmol) in 1.6 mL of EtOH was heated at 90C5 in a sealed tube for 5 h. Upon cooling to ambient temperature, the reaction mixture was concentrated and diluted with dichlorornethane (DCM). The organic layer washed with saturated aqueous NaHCO3 then dried over MgSO4 and concentrated. The crude product was purifiedsilica gel flash chromatography (eluted with 10% MeOH/DCM) to provide 0.8 g of product.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5049-61-6, its application will become more common.

Reference:
Patent; ARIAD PHARMACEUTICALS, INC.; GOZGIT, Joseph, M.; RIVERA, Victor, M.; SHAKESPEARE, William, C.; ZHU, Xiaotian; DALGARNO, David, C.; WO2013/162727; (2013); 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. 17231-51-5, name is 3-Amino-6-bromopyrazine-2-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 3-Amino-6-bromopyrazine-2-carbonitrile

Step 2: synthesis of 3,6-dibromopyrazine-2-carbonitrile (15) To a solution of copper(ii) bromide (1.432 g, 6.41 mmol) and tert-butylnitrite (0.769 mL, 6.41 mmol) in acetonitrile (40 mL) was added 3-amino-6-bromopyrazine-2-carbonitrile 14 (1.16 g, 5.83 mmol) in portions (in 2 h). The reaction was stirred for 2 h at 50 C. Quenched with 2N HCl solution and the resulting precipitate was collected. Purification by chromatography (CH2Cl2) gave pure 3,6-dibromopyrazine-2-carbonitrile 15 (820 mg, 53.5%). 1H-NMR (400 MHz, CDCl3) 8.66 (s, 1H). (m/z)=261, 263 and 265 (M+H)+.

According to the analysis of related databases, 17231-51-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Folmer, Brigitte Johanna Bernita; Man, de Adrianus Petrus Antonius; Gernette, Elisabeth Sophia; Corte Real Goncalves Azevedo, Rita; Ibrahim, Hemen; US2013/79341; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature 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.

tert-Butyl (3-(3-amino-6-bromopyrazine-2-carboxamido)-2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)benzyl)(methyl)carbamate (9B) A stirring, room temperature solution of 3-amino-6-bromopyrazine-3-carboxylic acid (2.18 g, 10 mmol), tert-Butyl (3-amino-2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)benzyl)(methyl) carbamate (4.61 g, 12 mmol) and HOBt (0.68 g, 5 mmol) in DMSO (16 mL) was treated with neat EDAC (4.79 g, 25 mmol). After 3 hours the reaction mixture was treated with water (50 mL) yielding a goo. The reaction mixture liquid was decanted off and the goo was treated with additional portions of water (40 mL each), again decanting between treatments. The goo was then partitioned between EtOAc (200 mL) and water (50 mL). The resulting organic phase was washed sequentially with saturated aqueous NaHCO3, 1N HCl, and then saturated aqueous NaHCO3 once again. The organic phase was then dried over Na2SO4, filtered and concentrated under reduced pressure to give an oil. This oil was placed under high vacuum overnight to yield 4.97 g (85%) of desired product as an amber oil. LC/MS: (>95%) (weak M+H=585; stronger M+23=607).

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; Atrin Pharmaceuticals LLC; Breslin, Henry Joseph; Gilad, Oren; Sperl, Gerhard; Brown, Eric J.; Butler, Laura; (77 pag.)US2017/291911; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 14508-49-7, name is 2-Chloropyrazine, 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 14508-49-7, Recommanded Product: 2-Chloropyrazine

Preparation 1; 4-Methyi-3,4,5,6-tetrahydro-2H-[1,2’lbip(at)rrazinyl-3′-carbaldehyde; n-BuLi (56 mmol, 22.4 mL, 2.5 M in hexanes) was added to tetrahydrofuran (300 mL) cooled to-78 C followed by the addition of 2,2-6,6-tetramethylpiperidine (52 mmol, 8.71 mL). The solution was removed from the cooling bath and stirred for 30 minutes and then cooled back to -78C. 2-chloropyrazine (40 mmol, 3.65 mL) was added dropwise, and the solution turned a reddish-brown color. After stirring 30 minutes, methylformate (60 mmol, 3.7 mL) was added and the reaction mixture was stirred for 2.25 hrs at -78C. Acetic acid (8 mL) was added and the mixture was warmed to 0C, was washed 3 times with 1: 1 brine-water, dried over sodium sulfate, and then concentrated in vacuo. The residue was dissolved in 1,4- dioxane (250 mL) and 1-methylpiperazine (60 mmol, 6.6mL) and potassium carbonate solution (8.28g in 60 mL of water) were added and the mixture was heated at 100C for 1.5 hours. After cooling to room temperature, the mixture was filtered through a Celite pad which was then washed with chloroform. The filtrate was concentrated in vacuo and purified by silica gel chromatography (100: 1:1 chloroform-methanol-ammonium hydroxide) to yield 3.3 g (40% yield for two steps) of 4-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-carbaldehyde; ¹3C NMR (100 MHz, CDC13) d 191.7,154.3, 145.3,134.5, 133.2, 55.1, 48.7, 46.3; MS (AP/CI) 207.2 (M+H)+.

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

Reference:
Patent; PFIZER PRODUCTS INC.; WO2005/113535; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 914452-71-4, 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 914452-71-4 as follows.

To a solution of 2-bromo-6-methylpyrazine (3 g, 17.3 mmol) in carbon tetrachloride (30 ml) were added at r.t. under an argon atmosphere N-bromo succinimide (3.39 g, 19.1 mmol) and benzoyl peroxide (420 mg, 1.73 mmol). The mixture was stirred for 24 fir, while a 75 W lamp was shining on the orange reaction mixture). The mixture was filtered, washed with CC14 and concentrated. The residue was dissolved in EtOAc, washed with sat aq NaHC03, brine, dried over MgS04, filtered and concentrated. The crude product was purified by silica gel chromatography using a heptane/EtOAc gradient as eluent, providing the title compound (1.88g, 43%) as brown solid.

According to the analysis of related databases, 914452-71-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; FLOHR, Alexander; GROEBKE ZBINDEN, Katrin; KOERNER, Matthias; LERNER, Christian; WO2013/178569; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-79-8, name is 6-Chloropyrazine-2-carboxamide, 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. COA of Formula: C5H4ClN3O

General procedure: 150 mg (0.952 mmol) of 5-Cl-PZA (1) or 6-Cl-PZA (2) was dissolved in ethanol together with triethylamine (1 eq., 96 mg, 0.952 mmol). Three equivalents of corresponding alkylamine were added to the reaction mixture and refluxed in ethanol generally for 6 hours. The completion of the reaction was checked by TLC chromatography (eluent: hexane/ethyl acetate, 1:2). The crude product was absorbed on silica by solvent evaporation and purified by flash chromatography (hexane/ethyl acetate gradient elution).

The synthetic route of 36070-79-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Servusova, Barbora; Paterova, Pavla; Mandikova, Jana; Kubicek, Vladimir; Kucera, Radim; Kunes, Jiri; Dolezal, Martin; Zitko, Jan; Bioorganic and Medicinal Chemistry Letters; vol. 24; 2; (2014); p. 450 – 453;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem