Month: May 2021

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., name: 3,5-Dichloropyrazine-2-carbonitrile

To a solution of 3,5-dichloropyrazine-2-carbonitrile (7.00 g, 40.23 mmol) in DMF (50 mL) was added (R)-(3-BOC-amino)piperidine (8.64 g, 44.25 mmol) and DIPEA (14.0 mL, 5.74 mmol) in a dropwise manner. The mixture was stirred at room temperature for 90 min. The mixture was diluted with ethyl acetate (500 mL), washed with water (x2), dried, and concentrated in vacuo. The residue was purified by flash chromatography with 0 to 20% ethyl acetate in DCM to isolate tert-butyl N-[(3R)-1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3- yl]carbamate (12.59 g, 93% 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; PHARMACYCLICS LLC.; ATALLAH, Gordana, Babic; CHEN, Wei; JIA, Zhaozhong, J.; POZZAN, Alfonso; RAVEGLIA, Lucal, Francesco; ZANALETTI, Riccardo; (815 pag.)WO2016/196776; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 6905-47-1, name is 2-Amino-6-methoxypyrazine, molecular formula is C5H7N3O, 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: C5H7N3O

2-Amino-6-methoxy-pyrazine (1.00 g, 8 mmol; CASNo. 6905-47-1 ) was dissolved in a mix of 1 :2 THF:MeCN (30 ml.), cooled to 0 0C, and treated with pyridine (0.664 g, 8.3 mmol) followed by the dropwise addition oi phenylchloroformate (1.3 g, 8.3 mmol) in THF (10 ml_). After stirring for 18 h, the resulting white solid was collected by filtration (1.3 g, 68%) and was used without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6905-47-1, its application will become more common.

Reference:
Patent; PFIZER INC.; WO2009/127948; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 55557-52-3,Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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.

EXAMPLE 13.1 (+-)-3-[(6R,8aS)[[(3-chlorophenyl)ethynyl]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl] pyrazine-2-carbonitrile A mixture of (+-)-(6R,8aS)-6-[(3-chlorophenyl)ethynyl]octahydropyrrolo[1,2-a]pyrazine (40 mg, 0.15 mmol), 2-chloro-3-cyanopyrazine(30 mg, 0.22 mmol), Et3N (0.1 mL) and THF (1.5 mL) was stirred at 80 C. for 4 h. The resulting mixture was concentrated and purified on silica gel column to provide product (44 mg, 81%). 1H NMR (300 MHz, CDCl3): delta (ppm) 1.62 (m, 1H), 1.85-2.25 (m, 5H), 3.02 (dd, 1H), 3.24-3.48 (m, 3H), 4.61 (dt, 2H), 7.29 (m, 3H), 7.45 (s, 1H), 8.02 (d, 1H), 8.27 (d, 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-Chloropyrazine-2-carbonitrile, its application will become more common.

Reference:
Patent; AstraZeneca AB; NPS PHARMACEUTICALS; US2007/37817; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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 486460-21-3, Formula: C6H7F3N4

To a solution of the acid (VII?) (300 mg, 0.90 mmol) and triazolopiperazine (VIII) (170 mg, 0.90 mmol) in CH2Cl2 (10 mL) is added N-hydroxybenzotriazole (150 mg, 1.08 mmol), and 10 minutes later, EDC (260 mg, 1.35 mmol). The mixture, under an inert atmosphere of N2, is magnetically stirred for 4 hours until completion, then a saturated solution of sodium bicarbonate (5 mL) is added and the mixture is extracted with dichloromethane. The combined organic phases are dried and evaporated under reduced pressure. The product is purified by flash chromatography, obtaining 406 mg (86% yield) of a crystalline white solid, compound (IX?). 1H NMR (300 MHz, d6-dmso, 100 C.) delta 7.4-7.2 (m, 7H), 6.90 (bs, 1H) 4.97 & 4.90 (AB system, J=12.9 Hz, 2×1H), 4.92 (s, 2H), 4.26-4.14 (m, 3H), 3.97 (t, J=5.5 Hz, 2H), 2.92 & 2.67 (2×dd, J=14.1, 4.9 Hz, 2×1H), 2.83-2.72 (m, 2H).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; CHEMO IBERICA S.A.; Rasparini, Marcello; Tufaro, Roberto Rocco; Minelli, Cosima; US2014/81026; (2014); 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 32974-92-8 as follows. Recommanded Product: 1-(3-Ethylpyrazin-2-yl)ethanone

Example 1882-(N-t-butylbenzyl)aminoethyl-2-(3-ethyl)-pyrazylketone 8658 2-acetyl-3-ethylpyrazine (151 mg), benzyl-t-butyl amine (149 mg), and paraformaldehyde (40 mg) were reacted in dioxane (0.2 ml) at 130 C. for 2 hours.NMR (CDCl3) 1.1 (m, 9H), 2.7 (m, 1H), 3.1 (m, 4H), 3.7 (m, 2H), 7-7.1 (m, 1H), 8.5-8.6 (m, 1H)TG 42 (3 mumol) 22 (10 mumol) 10 (30 mumol)SOCE 0 (10 mumol) 0 (30 mumol) 20 (100 mumol)IICR 50 (10 mumol) 90 (30 mumol) 100 (100 mumol)

According to the analysis of related databases, 32974-92-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Japan Science and Technology Agency; US2012/277423; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 5521-55-1, 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. 5521-55-1 name is 5-Methylpyrazine-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.

Step 1: To a solution of 2-methylpyrazine-5-carboxylic acid (10 g, 72.4 mmol) and TEA (20 mL, 108 mmol) in t-butanol (156 mL) and dioxanes (100 mL) was added diphenyl phosphorylazide (23.4 mL, 108 mmol) and the resulting solution was warmed at 100 C. for 3 hours and then cooled to room temperature overnight. The crude reaction mixture was concentrated in vacuo. Purification by chromatography (silica 0-15% ethyl acetate/hexanes) following trituration of impure fractions with ether afforded (5-methyl-pyrazin-2-yl)-carbamic acid tert-butyl ester (10.6 g, 70%): 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 1.56 (s, 9H) 2.51 (s, 3H) 8.02 (br. s., 1H) 8.07-8.14 (m, 1H) 9.18 (d, J=1.13 Hz, 1H).

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

Reference:
Patent; Brotherton-Pleiss, Christine E.; Walker, Keith A. M.; US2012/149718; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 312736-50-8, name is 3,5-Dichloropyrazine-2-carboxamide, 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 3,5-Dichloropyrazine-2-carboxamide

A mixture of 3,5-dichloropyrazine-2-carboxamide (3b, 450 mg, 2.34 mmol), 3-(methanesulfonyl)aniline (441 mg, 2.58 mmol), DIPEA (408 muL, 2.34 mmol) and 1,4-dioxane (20 mL) was stirred 110 C for 60 h. After the mixture was cooled, water was added, and the resulting slurry was extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (CHCl3/MeOH=100:0 to 50:1).The resulting product was washed with EtOAc to give 4b (425 mg,55%) as a pale yellow solid. 1H NMR (DMSO-d6): delta 3.24 (3H, s),7.55-7.77 (2H, m), 7.90-8.04 (1H, m), 8.06-8.36 (3H, m), 8.50 (1H, s),11.73 (1H, s); MS (FAB) m/z [M+H]+ 327.

The synthetic route of 3,5-Dichloropyrazine-2-carboxamide has been constantly updated, and we look forward to future research findings.

Reference:
Article; Iikubo, Kazuhiko; Kurosawa, Kazuo; Matsuya, Takahiro; Kondoh, Yutaka; Kamikawa, Akio; Moritomo, Ayako; Iwai, Yoshinori; Tomiyama, Hiroshi; Shimada, Itsuro; Bioorganic and Medicinal Chemistry; vol. 27; 8; (2019); p. 1683 – 1692;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 13924-94-2,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.

a. Methyl 5-((3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yI)amino)pyrazine-2- carboxylate (93). To a solution of 77 (1.1303 g, 4.02 mmol), 92 (0.5969 g, 3.90 mmol), CsCO3 (3.12 g, 9.58 mmol), rac-B1NAP (0.1868 g, 0.30 mmol) in toluene (4.5 mL) in a 100 mL round-bottomed flask was added Pd2(dba)3 (0.1780 g, 0.19 mmol). The solution was sparged with nitrogen for 5 mm., then a reflux condenser was fitted to the flask, the atmosphere was evacuated and back-filled with nitrogen (three times), and the reaction was heated to reflux with stirring in an oil bath (125- 120 C) for 22h. After cooling the reaction to room temperature, excess cesium carbonate and other solid particulates were filtered and washed with ethyl acetate, and the organic filtrate was concentrated in vacuo to give a crude product that was purified by column chromatography (150 mL Si02, 20% ethyl acetate:hexanes to 25% ethyl acetate: hexanes) to give 93 (0.8727 g, 63%) as a crystalline solid, m.p. 134.9-137.1 C: ?H NMR (400 MHz, CDC13)6 8.81 (d,J= 1.2, 1H), 8.08 (d,J = 1.6, 1H), 7.32 (s, 1H), 7.20 (s, 1H), 7.03 (br s, 1H), 3.95 (s, 3H), 2.22 (s, 3H), 1.68 (s, 4H), 1.28 (s, 6H), 1.24 (s, 6H); ?3C NMR (100.6 MHz, CDC13) 164.8, 154.3, 145.4, 144.1, 143.6, 132.8, 130.7,129.5, 129.3, 122.2, 52.3, 34.9, 34.8, 34.1, 33.9, 31.8, 31.7, 17.6; IR(neat) 3162, 2961, 1712, 1542, 1306, 1271, 1129 cm1 ES-MS (M+Na)+ calcd for C21H27N3O2Na 376.2001, found 376.2006.

The synthetic route of 13924-94-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY; WAGNER, Carl; MARSHALL, Pamela; JURUTKA, Peter; WO2015/130973; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 622392-04-5, A common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, molecular formula is C4H2BrIN2, 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 slurry of [1-BENZYL-4- [4- (4,] 4,5, [5-TETRAMETHYL- [1,] 3,2] dioxaborolan-2-yl) – benzenesulfonyl]-piperidine-4-carboxylic acid tert-butyl ester (1) (12.0 g, 22.2 mmol) in toluene (40 mL) was added solid 2-bromo-5-iodo-pyrazine (2) (6.98 g, 24.5 mmol, prepared in accordance with Example 21, Part B), 2 N [NA2C03] (25 mL), ethanol (2.5 mL), and Pd (dppf) Cl2 (0.90 [G,] 1.1 mmol). The resulting mixture was heated at [60C] for 16 hr. Afterward, the mixture was partitioned between EtOAc and water, and then filtered to remove insolubles. The organic layer was separated, washed with brine, dried over [MGS04,] and evaporated to a brown solid. The crude material was purified by flash column chromatography on silica gel (eluting with 5-80% ethyl acetate in hexane) to . afford 6.60 g (52% yield) of the desired product (3) as an off-white solid. LCMS: m/z =572.3, 574.3.

The synthetic route of 622392-04-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PHARMACIA CORPORATION; WO2004/811; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 19847-12-2,Some common heterocyclic compound, 19847-12-2, name is Pyrazinecarbonitrile, molecular formula is C5H3N3, 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: Synthesis of 5-(thiophen-3-yl)-1H-tetrazole (2a). 3-Thiophenecarbonitrile 1a (218 mg, 2 mmol), NaN3 (260 mg,4 mmol), CeCl3·7H2O (75 mg, 0.2 mmol), and 8 mL of a 3:1isopropanol/water mixture were added to a 30-mL Pyrexmicrowave vessel and capped. The microwave vessel wasthen placed in a multi-mode microwave reactor. The reactionwas magnetically stirred and heated for 1 hour at 160 C.The pressure in the vessel was not determined. The reactionwas monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reactionmixture was diluted with saturated aqueous sodium bicarbonate(20 mL) and washed with ethyl acetate (2 x 15 mL).The aqueous sodium bicarbonate layer was cooled with iceand acidified to a pH of 2 or less with concentrated hydrochloricacid, which was added drop-wise. The precipitateformed was extracted with ethyl acetate (3 x 15 mL). Thecombined organic layers were dried over anhydrous sodiumsulfate and decanted into a tared round bottom flask. Theorganic layer was concentrated under reduced pressure. Thetetrazole product was recrystallized from ethyl acetate andhexane. All reagents mentioned above were used unpurified.

The synthetic route of 19847-12-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Dudley, Joshua; Feinn, Liana; Defrancesco, Heather; Lindsay, Erica; Coca, Adiel; Roberts, Elizabeth Lewis; Medicinal Chemistry; vol. 14; 6; (2018); p. 550 – 555;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem