Month: February 2021

Some common heterocyclic compound, 13924-94-2, name is Methyl 5-aminopyrazine-2-carboxylate, molecular formula is C6H7N3O2, 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. Computed Properties of C6H7N3O2

19.3. Methyl 5-amino-6-bromopyrazine-2-carboxylate; Add 1.79 g (10.05 mmol) of N-bromosuccinimide to a solution of 1.4 g (9.14 mmol) of methyl 5-aminopyrazine-2-carboxylate in 10 mL of acetonitrile. Stir the reaction mixture for 2 h at 20 C. then distribute in 100 mL of EtOAc/water 1:1 mixture. Wash the organic phase with 2¡Á50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 0 to 50% of EtOAc. After concentration under reduced pressure, we obtain 1.66 g of methyl 5-amino-6-bromopyrazine-2-carboxylate in the form of yellow wax.Yield=78%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 13924-94-2, its application will become more common.

Reference:
Patent; Sanofi Aventis; US2009/318473; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 25513-93-3, A common heterocyclic compound, 25513-93-3, name is 3-Methylpyrazine-2-carbaldehyde, molecular formula is C6H6N2O, 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.

A mixture of 2,3-dimethylpyrazine (2Og, 18.5mmol), selenium dioxide (41.06g, 37mmol) and diatomeous earth (2Og) in EtOAc (500ml) was stirred and heated at 7O0C for 2 hours. The mixture was allowed to cool and the insoluble matter was removed by filtration EPO through diatomeous earth. The filtrate was washed with saturated aqueous sodium hydrogen carbonate solution and then saturated aqueous sodium chloride solution, dried (MgSO4) and the solvent removed by evaporation. The residue was suspended in water (100ml) and hydroxylamine (45ml of a 50% aqueous solution) was added. The mixture was stirred at ambient temperature for 18 hours and the mixture then extracted with EtOAc. The extracts were combined, washed with saturated aqueous sodium chloride solution, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with isohexane to give 3- methylpyrazine-2-carboxaldehyde oxime (9.65g, 38%); NMR Spectrum 2.67 (s, 3H), 8.23 (s, IH), 8.45-8.49 (m, 2H), 11.87 (s, IH).

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/106307; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 1458-18-0,Some common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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.

20.1. Methyl 3-amino-6-chloro-5-(2-methylphenyl)pyrazine-2-carboxylate; Put 5 g (22.5 mmol) of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 3.2 g (23.65 mmol) of 2-methylphenyl boronic acid in 45 mL of anhydrous toluene in a screw-top bottle. After dissolution, add 34 mL (67.6 mmol) of a 2N aqueous solution of sodium carbonate and degas the two-phase mixture for 30 min by bubbling with argon. Then add 1.3 g (1.13 mmol) of Pd(PPh3)4 and stir the reaction mixture vigorously at 110 C. for 48 h. After cooling, distribute the solution in 500 mL of EtOAc/brine 1:1 mixture and extract the aqueous phase again with 4¡Á50 mL of EtOAc. Combine the organic phases, dry over Na2SO4and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 0 to 20% of EtOAc. After concentration under reduced pressure, we obtain 2 g of methyl 3-amino-6-chloro-5-(2-methylphenyl)pyrazine-2-carboxylate in the form of yellow wax.Yield 50%

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-5,6-dichloropyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; Sanofi Aventis; US2009/318473; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

20721-17-9, name is 5-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. category: Pyrazines

2-HYDROXY-5-METHYLPYRAZINE (0.984g, 8.94 mmol) was refluxed in 15 mL PHOSPHOROXY- chloride for 1.5h. The reaction mixture was slowly poured into ice and adjusted to pH6 by addition of sodium carbonate. The mixture was extracted six times with ethyl acetate (50 mL each). The combined organic extracts were dried with sodium sulfate, filtered and eva- porated. The crude product was used without any further purification for the next step.

The synthetic route of 20721-17-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2004/80998; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4858-85-9, name is 2,3-Dichloropyrazine, 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: 2,3-Dichloropyrazine

Under a nitrogen atmosphere, in 25 ml substrate is added into the test tube reactor 3dam (0.2mmol, 29.6 mg), 1-chlorobutane (3.0mmol, 276.0 mg), PdCl2(dppf) (0.02mmol, 14.6 mg), DPPF (0.01mmol, 5.6 mg), Cs2CO3(0.3mmol, 195.0 mg), Na2S2O35H2O (0.5mmol, 248.0 mg), DMSO (4.0 ml) and glycol (0.1 ml). Heating the reaction system to 120 C for reaction. TLC detection after the reaction is ended, the system is cooled to room temperature. Hydrosolvent quenching reaction with saturated ammonium chloride, extracted with ethyl acetate (3*10 ml), column chromatography purification to obtain the product 3da (88%).

The synthetic route of 4858-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; East China Normal University; JIANG, XUE FENG; QIAO, ZONG JUN; (33 pag.)CN103848767; (2016); B;,
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. 313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile, A new synthetic method of this compound is introduced below., Safety of 3,5-Dichloropyrazine-2-carbonitrile

Step 1: To a mixture of 3,5-dichloropyrazine-2-carbonitrile (500 mg, 2.84 mmol) and D-valinamide HCl salt (476 mg, 3.12 mmol) in AcCN (10 mL) was added DIPEA (1.11 mL, 6.25 mmol). After stirring at room temperature for 4 h, it was diluted with EtOAc, washed with sat. NaHCO3, organic layer was separated and washed with brine, dried and concentrated to give (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-methylbutanamide (740 mg).

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; Portola Pharmaceuticals, Inc.; Song, Yonghong; Xu, Qing; Jia, Zhaozhong J.; Kane, Brian; Bauer, Shawn M.; Pandey, Anjali; US2013/131040; (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. 61655-77-4, name is 2-Chloro-6-(4-methylpiperazin-1-yl)pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 2-Chloro-6-(4-methylpiperazin-1-yl)pyrazine

General procedure: A microwave tube filled with compound 2 (0.35 mmol), alkoxy heteroaromatic chloride or amine heteroaromatic chloride (0.38 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.010 mmol), 2 M potassium carbonate (1.7 mmol) in dioxane : ethanol (2 : 3) was heated in the microwave reactor at power 100 W and 120 C for 10 min. After solvent was removed in vacuo, the residue was treated with ethyl acetate and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel.

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 61655-77-4.

Reference:
Article; Lee, Jinho; Park, Jongseong; Hong, Victor Sukbong; Chemical and Pharmaceutical Bulletin; vol. 62; 9; (2014); p. 906 – 914;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 91476-80-1, These common heterocyclic compound, 91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[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 3 4-[[3-(6,8-dihydro-5H-imidazo[1,2-c]pyrazine-7-carbonyl)-4-fluoro-phenyl]methyl]-2H-phthalazin-1-one 2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (323 mg, 1.08 mmol) was dissolved in 5 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (614 mg, 1.63 mmol), 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine 4c (200 mg, 1.63 mmol) and N, N-diisopropylethylamine (0.4 mL, 2.16 mmol). After stirring for 12 hours, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by thin layer chromatography with elution system A to obtain 4-[[3-(6,8-dihydro-5H-imidazo[1,2-c]pyrazine-7-carbonyl)-4-fluoro-phenyl]methyl]-2H-phthalazin-1-one 4 (10 mg, yield 2.3%) as a white solid. MS m/z (ESI): 404.1 [M+1] 1H NMR (400 MHz, CDCl3): delta 10.07 (br. s, 1H), 8.53 (d, 1H), 7.96 (m, 1H), 7.83 (m, 3H), 7.51 (m, 1H), 7.30 (m, 2H), 6.01 (t, 1H), 4.73 (d, 2H), 4.35 (s, 2H), 1.60 (m, 2H), 1.34 (m, 2H)

The synthetic route of 91476-80-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JIANGSU HANSOH PHARMACEUTICAL CO., LTD.; Tang, Peng Cho; Li, Xin; Li, Xiangqin; Chen, Yang; Wang, Bin; Zhu, Zhe; US2013/131068; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 13484-56-5, These common heterocyclic compound, 13484-56-5, name is 3-Chloro-6-methoxypyrazin-2-amine, 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.

Sodium hexamethyldisilazane (1M solution in THF; 6.7 ml) was added dropwise to amixture of 3-amino-2-chloro-5-methoxypyrazine (0.64 g), 4-chloro-7-(2-chloroethoxy)-3-cyano-6-methoxyquinoline (J. Med. Chem., 2001,44, 3965-3977; 1 g) andDMF (10 ml) thathad been cooled to 0C. The mixture was stirred at 0C for 5 minutes and at ambienttemperature for 30 minutes. Acetic acid (0.38 ml) was added and the resultant mixture wasevaporated. The residue was partitioned between methylene chloride and a 5% aqueoussodium bicarbonate solution. The organic solution was dried over magnesium sulphate andevaporated. The residue was triturated under diethyl ether and the resultant solid was isolated.There was thus obtained the title compound as a solid (0.98 g); Mass Spectrum: M+H1″ 420and 422.

The synthetic route of 13484-56-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/108703; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 59489-71-3, name is 2-Amino-5-bromopyrazine, 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. SDS of cas: 59489-71-3

Example 71 2 (R)- (3-CHLORO-METHANESULFONYL-PHENYL)-3-CYCLOPENTYL-N- [5- (3-METHOXY-PHENYL)- PYRAZIN-2-YL]-PROPIONAMIDE [000334] Nitrogen was bubbled through a solution of 3-methoxyphenyl boronic acid (393 mg, 2.59 mmol), 2-AMINO-5-BROMOPYRAZINE (300 mg, 1.72 mmol), sodium carbonate (603 mg, 5.69 mmol), dimethoxyethane (10 mL), and water (3 mL) for 15 min. After this time, the solution was treated with dichlorobis (triphenylphosphine) palladium (II) (121 mg, 0.17 mmol), and the resulting reaction mixture was heated at 90C for 2 days. The reaction was then poured into water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 40/60 hexanes/ethyl acetate) afforded 5- (3-METHOXY-PHENYL)-PYRAZIN-2-YLAMINE (218 mg, 63%) as a light yellow solid: mp 113.2-115. 5C ; EI-HRMS m/e calcd for CLLHIIN3O (M+) 201.0902, found 201.0905.

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2004/52869; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem