Month: June 2021

Reference of 123-32-0, A common heterocyclic compound, 123-32-0, name is 2,5-Dimethylpyrazine, molecular formula is C6H8N2, 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.

Preparation of 3,6-dimethyl-2- (2-thenoyl) pyrazine, comprising the steps of:(1) 2,5-dimethyl pyrazine take 0.2mmol, 2- benzoyl-carboxylic acid thiophene 0.4mmol, 0.02 mmol silver phosphate, potassium persulfate 5mL reaction tube was placed 0.4mmol, 1.4mL was added dichloro methane, 0.6 mL of distilled water was added, and the reaction mixture was placed in a 5mL tube and placed in an oil bath at 40 heated, reaction 24h, cooled to room temperature to obtain a reaction solution;(2) The step (1) the resulting reaction mixture was directly concentrated to give a concentrate, the concentrate with ethyl acetate / petroleum ether = 1/2 (v / v) as the developing solvent, separation by thin layer chromatography to give 30mg target The product, in 69% yield.

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; Henan Agricultural University; Wu Zhiyong; Zhao Mingqin; Li Yuan; (10 pag.)CN108101856; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4744-50-7, name is 2,3-Pyrazinecarboxylic anhydride, 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. Formula: C6H2N2O3

A solution of (S)-[1-(trans-4-amino-cyclohexyl)-2-oxo-2-pyrrolidin-1-yl-ethyl]-carbamic acid tert-butyl ester (176 mg, 0.5 mmol) and 2,3-pyrazinecarboxylic anhydride (75 mg, 0.5 mmol) in THF (5 mL) was stirred at reflux for 2 hours. The mixture was concentrated to dryness, treated with acetic anhydride (4 mL) and heated to reflux for 3 hours. The excess acetic anhydride was removed under high vacuum and the residue was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic phases were washed with water (3×) and brine, dried over magnesium sulfate and concentrated to dryness. The residue was triturated with ether and the light brown solid was isolated. This solid was dissolved in 4 N hydrogen chloride/dioxane (1 mL) and the solution was stirred at room temperature for 1 hour. Ether (2 mL) was added and the precipitate was collected and dried (17 mg, 8.6%). MS m/z 358 (MH+).

The synthetic route of 4744-50-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc; US2005/234065; (2005); 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., SDS of cas: 33332-25-1

Saturated aqueous sodium hydrogen carbonate solution (5.00 ml) was added to methyl 5-chloropyrazine-2-carboxylate (173 mg, 1.00 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (371 mg, 1.20 mmol), palladium(II) acetate (11 mg, 0.05 mmol) and triphenylphosphine (52 mg, 0.20 mmol) in 1,2-dimethoxyethane (5.00 ml) at 25 C. under nitrogen. The resulting mixture was stirred at 80 C. for 4 h. The reaction mixture was diluted with water (50 mL) and washed with EtOAc (50 mL). The aqueous layer was adjusted to pH 1 using HCl (2M aqueous solution) and extracted with EtOAc (2×50 mL). The combined organics were dried over MgSO4 and concentrated under reduced pressure to afford 5-[1-[(2-methylpropan-2-yl)oxycarbonyl]-3,6-dihydro-2H-pyridin-4-yl]pyrazine-2-carboxylic acid (305 mg, 100%) as a yellow solid. This was used directly in the next reaction, with no further purification. 1H NMR (DMSO, 399.9MHz) delta1.45 (9H, s), 2.64 (2H, d), 3.58 (2H, t), 4.13 (2H, d), 7.02 (1H, s), 9.01 (1H, d), 9.12 (1H, d), 13.40 (1H, br s). MS: m/z 306 (MH+).

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; US2008/153812; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 939412-86-9,Some common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, molecular formula is C5H7Cl2N3, 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 (trans)-6-oxooctahydro-l H-quinolizine-3 -carboxylic acid (520 mg, 2.64 mmol), (3-chloropyrazin-2-yl)methanamine hydrochloride (570 mg, 3.17 mmol), HATU (1.50 g, 3.95 mmol) and TEA (0.79 g, 7.91 mmol) in DCM (13 mL) was stirred at 25 C overnight. The mixture was quenched with H20 (40 mL) and extracted with DCM (15 mL*3).The combined organic layerswere dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product.The crude product was purified by column chromatography on silica gel eluting with PE / THF (0-60%) to give (trans)- N-((3-chloropyrazin-2-yl)methyl)-6-oxooctahydro-l H-quinolizine-3 -carboxamide (0.7 g, 82.35%) as a light yellow solid. 1H NMR (400MHz, CDC13) delta = 8.53 – 8.41 (m, 1H), 8.33 (d, J=2.5 Hz, 1H), 6.96 (br. s., 1H), 5.08 – 4.88 (m, 1H), 4.73 – 4.61 (m, 2H), 3.40 – 3.26 (m, 1H), 2.72 – 2.57 (m, 1H), 2.47 – 2.28 (m, 3H), 2.12 – 2.00 (m, 2H), 1.89 – 1.77 (m, 4H), 1.73 – 1.62 (m, 1H), 1.58 – 1.47 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (3-Chloropyrazin-2-yl)methanamine hydrochloride, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; KOZLOWSKI, Joseph; YU, Wensheng; ANAND, Rajan; YU, Younong; SELYUTIN, Oleg B.; GAO, Ying-Duo; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/114185; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 68774-77-6, A common heterocyclic compound, 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C5H3ClN4, 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.

To a solution of the product of Example 365A (70 mg, 0.153 mmol) in N,N- dimethylformamide (1 mL) was added 8-chloro-[l,2,4]triazolo[4,3-a]pyrazine (35.5 mg, 0.230 mmol) and N,N-diisopropylethylamine (0.080 mL, 0.460 mmol). The reaction mixture was stirred for 4 days at 70 C and then was purified by preparative HPLC [Waters XBridge CI 8 5 mupiiota OBD column, 30 x 100 mm, flow rate 40 mL/minute, 5-100% gradient of acetonitrile in buffer (0.1 % trifluoroacetic acid)] to give the title compound (15 mg, 0.026 mmol, 17% yield). JH NMR (400 MHz, DMSO-<) delta ppm 9.17 (s, IH), 7.75 (d, J = 4.8 Hz, IH), 7.54 (s, IH), 7.45 (t, J = 8.9 Hz, IH), 7.23 (d, J = 4.9 Hz, IH), 7.00 (dd, J = 11.4, 2.9 Hz, 2H), 6.79 (ddd, J = 9.0, 2.9, 1.2 Hz, IH), 4.42 (s, 2H), 4.17 - 4.14 (m, 2H), 2.64 - 2.50 (m, IH), 2.35 (ddd, J = 12.8, 9.4, 2.9 Hz, IH), 2.27 - 2.13 (m, IH), 2.04 - 1.77 (m, 8H); 19F NMR (376 MHz, DMSO-<) delta ppm - 75.00, -114.17; MS (ESI+) m/z 461 (M+H)+ . The synthetic route of 68774-77-6 has been constantly updated, and we look forward to future research findings. Reference:
Patent; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; FROST, Jennifer, M.; PLIUSHCHEV, Marina, A.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; SWEIS, Ramzi, Farah; DART, Michael, J.; RANDOLPH, John, T.; MURAUSKI, Kathleen; (674 pag.)WO2019/90076; (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. 5049-61-6, name is Pyrazin-2-amine, A new synthetic method of this compound is introduced below., Quality Control of Pyrazin-2-amine

Step 1: 2-amino-5-bromopyrazine. To a stirred, cooled (0 C) solution of amino pyrazine (5.0 g, 52.6 mmol) in methylene chloride (200 mL) was added N-bromosuccinimide (9.39 g, 52.8 mmol). After stirring for 24 hours, the reaction was washed with aqueous 10% sodium carbonate (3*50 mL), water (50 mL), then dried (MgSO4), and filtered. The filtered material was concentrated under reduced pressure, taken up in minimal ethyl acetate (5 mL) followed by hexanes (200 mL). Yellow crystals formed which were filtered and dried. (56 % yield).

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Keegan, Kathleen S.; Kesicki, Edward A.; Gaudino, John Joseph; Cook, Adam Wade; Cowen, Scott Douglas; Burgess, Laurence Edward; US2003/69284; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 solution of methyl 3-amino-6-bromopyrazine-2-carboxylate (500 mg, 2.16 mmol), tetrakis(triphenylphosphine)palladium(0) (124 mg, 0.108 mmol) and sodium methanethiolate (306 mg, 4.31 mmol) in DMF (10 ml) was sealed in a nitrogen flushed pressure tube. The pressure tube was heated at 50 C for 2 h then allowed to cool to RT. The reaction mixture was diluted with EtOAc (30 ml) then washed with hydrochloric acid (1 M, 2 x 25 ml). A precipitate formed, which was removed by filtration. The filtrate was dried over MgS04 and evaporated. The crude material thus obtained was purified by flash column chromatography on C18 (60 g). The column was eluted with MeC iHiO + 0.1% formic acid using the following gradient (%MeCN, column volumes): 10%, 2 CV; 10-100%, 20 CV; 100%, 2 CV. The desired fractions were combined and evaporated to yield the product as a dark yellow solid (77 mg, 19%).1H NMR (250 MHz, DMSO-de) delta 12.89 (s, 1 H), 8.24 (s, 1 H), 7.25 (s, 2H), 3.30 (s, 3H). LC/MS (System A): m/z (ESI+) = 186 [MH+], Rt = 0.72 min, UV purity = 98%.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ENTERPRISE THERAPEUTICS LIMITED; MCCARTHY, Clive; HARGRAVE, Jonathan David; HAY, Duncan Alexander; SCHOFIELD, Thomas Beauregard; WENT, Naomi; (111 pag.)WO2017/221008; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 14508-49-7, 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. 14508-49-7, name is 2-Chloropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 2-chloropyrazine 1 (0.8 mL, 8.96 mmol) in dry 1,2-dichloroethane (15 mL) was added 3-chloroperbenzoic acid (mCPBA, 2.47 g, 14.34 mmol, 1.6 equiv). The reaction mixture was stirred at 65 C for 30 h and then cooled to room temperature. The mixture was washed with a 1 M NaOH solution, a saturated Na2S2O3 solution, water and then dried over Na2SO4. The filtrate was concentrated under reduced pressure, to give the title compound as white solid (0.95 g, 81%). 1H NMR (300 MHz, CDCl3) delta 8.24 (d, J = 4.1 Hz, 1H, H-6), 8.18-8.10 (m, 1H, H-3), 8.01 (dd, J = 4.1, 1.5 Hz, 1H, H-5). 13C NMR (75 MHz, CDCl3) delta 151.9 (C-2), 146.1 (C-6), 133.6 (C-3), 133.3 (C-5).

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, 2-Chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Plebanek, Elzbieta; Lescrinier, Eveline; Andrei, Graciela; Snoeck, Robert; Herdewijn, Piet; De Jonghe, Steven; European Journal of Medicinal Chemistry; vol. 144; (2018); p. 93 – 103;,
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., Computed Properties of C9H16N2O2

Step 4: (2S,5R)-2-(3-(Benzyloxy)-5-bromopentyl)-5-isopropyl-3,6-dimethoxy-2,5- dihydropyrazine (S6) [0523] To a dry-ice / acetone cooled solution of scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), was dropwise added n-BuLi (2.5 M, 14.1 mL, 0.035 mol) for 30 min. After addition, the reaction was stirred at this temperature for 30 min, followed by dropwise addition of a solution of scheme 5-8 compound S4 (13.6 g, 0.04 mol) in THF (20 mL). The reaction mixture was stirred at this temperature for another 30 min and allowed to stir at room temperature for 16 h. Then the reaction was quenched with aq. H4CI (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic layers are washed with brine, dried over anhydrous Na2SC”4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10: 1) to give the title compound (6 g, yield 50.4%>) and scheme 5-8 compound S4 (4.8 g) was recovered.

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 109838-85-9.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (317 pag.)WO2017/35413; (2017); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5521-55-1,Some common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, molecular formula is C6H6N2O2, 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.

To the starting material 5-methylpyrazine-2-carboxylic acid (2.0 g 0.145 mmol), methanol(20.0 mL), sulfuric acid (0.2 mL) and molecular sieves 4 A (catalytic) was added and thereaction mixture was heated to reflux for 8 h. TLC revealed complete consumption ofstarting material after 8 h. The solvent was evaporated, EtOAC (25 mL) was added andwater (10 mL) was added and the layers were separated. The aqueous layer wasextracted twice with EtOAC (25 mL) and organic layers were pooled together, washedwith brine solution (25 mL). The organic layer was dried over sodium sulfate andevaporated under reduced pressure to dryness. The compound was purified and washedusing diethyl ether (10 mL). Yield: 81%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Methylpyrazine-2-carboxylic acid, its application will become more common.

Reference:
Article; Balasubramaniam, Sivaraman; Vijayan, Sajith; Goldman, Liam V.; May, Xavier A.; Dodson, Kyra; Adhikari, Sweta; Rivas, Fatima; Watkins, Davita L.; Stoddard, Shana V.; Beilstein Journal of Organic Chemistry; vol. 16; (2020); p. 628 – 637;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem