Category: Pyrazines

Application of 1379338-74-5,Some common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, molecular formula is C7H3Cl2N3, 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.

Intermediate 33: 1,1-Dimethylethyl-2-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)amino]methyl}-4-morpholinecarboxylate 1,1-Dimethylethyl-2-(aminomethyl)-4-morpholinecarboxylate (60 mg, 0.28 mmol) was dissolved in N-methyl-2-pyrrolidinone (NMP) (1 mL) and to this was added DIPEA (0.07 mL, 0.38 mmol) and 5,7-dichloropyrido[3,4-b]pyrazine (50 mg, 0.25 mmol). This was heated at 130 C. for 30 min. The reaction mixtures were partitioned between ethyl acetate (50 ml) and water (50 mL) and the organic layer washed with water (50 mL), dried over a hydrophobic frit and concentrated in vacuo to yield an orange gum. It was dissolved in DCM and passed through silica (10 g) eluting with a 10-40% ethyl acetate in cyclohexane gradient. Appropriate fractions were combined and concentrated in vacuo to yield the title compound as a yellow solid, 91 mg. LCMS (Method B): Rt=1.17 min, MH+ 380

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5,7-Dichloropyrido[3,4-b]pyrazine, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Atkinson, Stephen John; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander G.; Shipley, Tracy Jane; Wilson, David Matthew; Watson, Robert J.; US2014/5188; (2014); 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., SDS of cas: 16298-03-6

Hydrazine hydrate (34 mL, 1.1 mol) was added portionwise to a stirred suspension of methyl 3-aminopyrazine-2-carboxylate 37 (21.3 g, 139 mmol) in ethanol (65 mL) at room temperature. The resulting slurry was stirred at 60 °C for 2 h, cooled to room temperature, and filtered. The solid was washed with cold ethanol (2 x 25 mL) and dried to a constant weight to afford 3-aminopyrazine-2-carbohydrazide (20.75 g, 97percent) as a beige solid. TBTU (5.77 g, 18.0 mmol) was added portionwise over 15 min to a stirred suspension of DIPEA (8.5 mL, 49 mmol), 1-methylcyclopropanecarboxylic acid (1.63 g, 16.3 mmol) and 3-aminopyrazine-2-carbohydrazide (2.50 g, 16.3 mmol) in acetonitrile (40 mL). The mixture was stirred at 80 °C for 20 min, and then cooled to 0 °C. DIPEA (8.5 mL, 49 mmol) followed by 4-methylbenzene-1-sulfonylchloride (9.34 g, 49 mmol) were added over a period of 15 min. The reaction mixture was brought to reflux and allowed to stir at room temperature for 14 h. The mixture was concentrated, and the residue was diluted with DCM, washed with water and brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 40percent ethyl acetate in dichloromethane. After evaporation of the solvent, the resulting solid was triturated with diethyl ether, filtered, washed with the minimum of diethyl ether and dried to afford 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.12 g, 60percent). NBS (1.87 g, 10.5 mmol) was added portionwise to a solution of 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.08 g, 9.6 mmol) in THF (30 mL). The reaction mixture was stirred at room temperature for 16 h and concentrated. The residue was dissolved in dichloromethane (150 mL), washed with water (2 x 40 mL), brine, dried over magnesium sulfate and concentrated. After evaporation of the solvents, the crude product was purified by flash chromatography on silica gel eluting with 0 to 10percent ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 5-bromo-3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.50 g, 88percent) as a yellow solid. Bis(triphenylphosphine)palladium(II) chloride (59 mg, 0.08 mmol) was added in one portion to a stirred solution of 5-bromo-3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (500 mg, 1.69 mmol) and hexamethyldistannane (0.49 mL, 2.4 mmol) dissolved in dioxane (8 mL) under argon. The resulting suspension was stirred at 80 °C for 1 h. The mixture was evaporated. The crude product was purified by flash chromatography on silica gel eluting with 10 to 30percent ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)-5-(trimethylstannyl)pyrazin-2-amine 38a (314 mg, 49percent) as a yellow crystalline solid.

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:
Article; Barlaam, Bernard; Cosulich, Sabina; Delouvrie, Benedicte; Ellston, Rebecca; Fitzek, Martina; Germain, Herve; Green, Stephen; Hancox, Urs; Harris, Craig S.; Hudson, Kevin; Lambert-Van Der Brempt, Christine; Lebraud, Honorine; Magnien, Francoise; Lamorlette, Maryannick; Le Griffon, Antoine; Morgentin, Remy; Ouvry, Gilles; Page, Ken; Pasquet, Georges; Polanska, Urszula; Ruston, Linette; Saleh, Twana; Vautier, Michel; Ward, Lara; Bioorganic and Medicinal Chemistry Letters; vol. 25; 22; (2015); p. 5155 – 5162;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 25911-65-3, name is 3-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. HPLC of Formula: C5H4N4

EXAMPLE 4 Synthesis of 3-Amino-6-bromopyrazine-2-carbonitrile (Intermediate 3) To a solution of intermediate 2 (1.7 g, 14 mmol) in acetic acid (40 mL) at RT was added bromine (0.95 mL, 19 mmol) slowly. The resulting mixture was heated at 60 C. for 30 min and then cooled to RT. The mixture was poured into ice water and the resulting solid filtered. After thoroughly washed with water, the title compound was obtained as a yellow solid (2.3 g, 83%). 1H NMR (500 MHz, DMSO-d6): delta 8.44 (s, 1H), 7.60 (br s, 2H). MS (ES+): m/z 199 (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 25911-65-3, its application will become more common.

Reference:
Patent; TargeGen, Inc.; US2007/259876; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, molecular formula is C6H9N3, 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. SDS of cas: 91476-80-1

6-chloro-2-(l,l-dimethylethyl)-l,3-benzoxazole-7-sulfonyl chloride (457 mg) was dissolved in 2.5 mL DCM and the solution was cooled to 0 0C. Triethylamine (0.41 mL) was added followed by 5,6,7,8-tetrahydroimidazo[l,2-alpha]pyrazine (201 mg) dissolved in 2.5 mL DCM. The reaction mixture was stirred at 0 0C to room temperature over night. The reaction was quenched with water and extracted with DCM (3×10 mL). The combined organic layers were dried Na2SOzI, filtered and the solvent was removed in vacuo. The crude product was purified by column chromatography eluting with a gradient of 0 to 20% MeOH in DCM yielding 409 mg of product. Rf: 0.57 (10% MeOH in DCM).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 91476-80-1, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/124423; (2007); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 41110-28-5, name is 3-Methylpyrazine-2-carboxylic acid, 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. category: Pyrazines

Example 1.1: Preparation of 3-methyl-pyrazine-2-carboxylic acid ethyl esterTo a solution of 3-methyl-pyrazine-2-carboxylic acid (10 g) (commercially available) and jV,7V-dimethylformamide (“DMF”) (1 drop) in dichloromethane (20 ml) at ambient temperature was added drop wise oxalyl chloride (2.57 ml). The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was concentrated and the residue dissolved in dichloromethane (20 ml). Triethylamine (4.04 ml) was added to this solution followed by drop wise addition of ethanol (10 ml). The reaction mixture was stirred at ambient temperature for one hour and then concentrated. The residue was purified by chromatography on silica gel (eluent: 0-10% v/v ethyl acetate in zso-hexane) to give 3- methyl-pyrazine-2-carboxylic acid ethyl ester (9.85 g). MH+ = 167, RT = 0.73 min (Method A). IH-NMR (400 MHz, CDCl3): 8.61 (d, IH), 8.54 (d, IH), 4.49 (q, 2H), 2.85 (s, 3H), 1.46 (t, 3H) ppm.

The synthetic route of 3-Methylpyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SYNGENTA LIMITED; WILLETTS, Nigel, James; MULHOLLAND, Nicholas, Phillip; WORTHINGTON, Paul, Anthony; AVERY, Alaric, James; WO2010/130970; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 74290-67-8, 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. 74290-67-8 name is 2-Amino-5-bromo-3-methylpyrazine, 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.

A solution of 5-bromo-3-methyl-pyrazin-2-amine (1000 mg, 5.32 mmol), phenol (650 mg, 6.91 mmol), Cs2C03 (2600 mg, 7.98 mmol), Cul (203 mg, 1.06 mmol), and Nu,Nu-dimethylgly cine (110 mg, 1.06 mmol) in dioxane (5 mL) was degassed and heated to 90 C under N2 for 12 h. After cooling to room temperature, the mixture was diluted with EtOAc (100 mL) and water (100 mL) and the organic phase collected. The aqueous layer was extracted again with EtOAc (100 mL) and the combined organic layers were dried over anhydrous MgSC^ and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a yellow oil (533 mg, 49.8% yield). MS (ESI): mass calcd. for CnHnN30, 201.1; m/z found, 202.1 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-5-bromo-3-methylpyrazine, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; ARORA, Nidhi; BACANI, Genesis M.; BARBAY, Joseph Kent; BEMBENEK, Scott D.; CAI, Min; CHEN, Wei; DECKHUT, Charlotte Pooley; EDWARDS, James P.; GHOSH, Brahmananda; HAO, Baoyu; KREUTTER, Kevin; LI, Gang; TICHENOR, Mark S.; VENABLE, Jennifer D.; WEI, Jianmei; WIENER, John J. M.; WU, Yao; ZHU, Yaoping; ZHANG, Feihuang; ZHANG, Zheng; XIAO, Kun; (1000 pag.)WO2017/100668; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 21943-17-9,Some common heterocyclic compound, 21943-17-9, name is 5-Bromo-3-chloropyrazin-2(1H)-one, molecular formula is C4H2BrClN2O, 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: A solution of 56 (1.50 g, 7.16 mmol), the appropriate secondary amine (8.59 mmol, 1.20 equiv) and diisopropylethylamine (1.50 mL, 8.59 mmol) in n-butanol (15 mL)was heated in a microwave reactor using variable wattage to 140 C for 1 h. The mixture was concentrated and purified by flash column chromatography on silica, eluting with 9:1 dichloromethane/methanol, to give gave 58-63.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-3-chloropyrazin-2(1H)-one, its application will become more common.

Reference:
Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728,16;; ; Article; Caldwell, John J.; Veillard, Nicolas; Collins, Ian; Tetrahedron; vol. 68; 47; (2012); p. 9713 – 9728;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, 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: C5H4Br2N2O

A mixture of tert-butyl 4-(4-aminophenyl)piperidine-l-carboxylate (2.5 g, 9.06 mmol) and 3,5-dibromo-l-methylpyrazin-2(lH)-one (2.2 g, 8.23 mmol) in isopropanol (30 mL) was heated at 85 °C for 15 h. After the reaction was finished, it was filtered and the solid was washed with isopropanol to afford 282a as a white solid (2.9 g, 80 ).LCMS: (M+H)+ 463

The synthetic route of 87486-34-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GILEAD CONNECTICUT, INC.; GENENTECH, INC.; BARBOSA, Antonio, J., M.; BLOMGREN, Peter, A.; CURRIE, Kevin, S.; KRISHNAMOORTHY, Ravi; KROPF, Jeffrey, E.; LEE, Seung H.; MITCHELL, Scott A.; ORTWINE, Daniel; SCHMITT, Aaron, C.; WANG, Xiaojing; XU, Jianjun; YOUNG, Wendy; ZHANG, Honglu; ZHAO, Zhongdong; ZHICHKIN, Pavel E.; WO2011/140488; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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. Safety of 3-Amino-6-bromopyrazine-2-carboxylic acid

Step 1. Synthesis of tert-butyl (l-(2-(3-amino-6-bromopyrazine-2-carboxamido)pyridin- 3-yl)-4-methylpiperidin-4-yl)carbamate. In a 100 mL round bottom flask equipped with a magnetic stirrer HBTU (2.23 gm, 5.87 mmol), 3-amino-6-bromopyrazine-2-carboxylic acid (1.17 gm, 5.39 mmol), and N-ethyl-N- isopropylpropan-2-amine (1.28 mL, 7.34 mmol) were allowed to stir in DMF (15 ml) for 15 minutes whereupon tert-butyl (l-(2-aminopyridin-3-yl)-4-methylpiperidin-4-yl)carbamate (1.5 gm, 4.9 mmol) was added in one portion. Reaction was allowed to stir for 16hr. Reaction was then poured into DMF and extracted thrice with 50 mL ethyl acetate. Organic extracts were combined and dried with brine followed by anhydrous sodium sulfate. The residue was purified by silica gel using gradient chromotography ethanol – ethyl acetate 0 -10% which yielded pure tert-butyl (l-(2-(3-amino-6-bromopyrazine-2-carboxamido)pyridin-3-yl)-4-methylpiperidin-4- yl)carbamate (1.86 gm, 67.5% yield) upon evaporation of fractions containing the desired product. LC-MS (Acidic method): ret.time= 1.17 min, M+H = 508.3.

The synthetic route of 3-Amino-6-bromopyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; LUZZIO, Michael Joseph; PAPILLON, Julien; VISSER, Michael Scott; (213 pag.)WO2016/20864; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 957344-74-0, name is 5,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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: 957344-74-0

A mixture of known compound 7 (2.75g, 9.90mmol), cyclopropylamine (3.4mL, 49.50mmol) and N, N-diisopropylethylamine (3.5mL, 19.80mL) in 1,4-dioxane (33mL) was stirred at 100C for 16h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with saturated aqueous NaHCO3. The organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (Hexanes:EtOAc=1:2) to afford the title compound 9 (2.3g, 92%). 1H NMR (300MHz, DMSO-d6) delta 7.88 (s, 1H), 7.82 (br, 1H), 7.58 (s, 1H), 7.49 (s, 1H), 2.85 (m, 1H), 0.68 (m, 2H), 0.63 (m, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 957344-74-0, its application will become more common.

Reference:
Article; Kang, Seok Jong; Lee, Jung Wuk; Chung, Shin Hyuck; Jang, Sun Young; Choi, Jaeyul; Suh, Kwee Hyun; Kim, Young Hoon; Ham, Young Jin; Min, Kyung Hoon; European Journal of Medicinal Chemistry; vol. 163; (2019); p. 660 – 670;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem