Category: Pyrazines

These common heterocyclic compound, 5049-61-6, name is Pyrazin-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. 5049-61-6

Stage 1. 3, 5-Dibromopyrazin-2-amine To a solution of aminopyrazine (11.36 g, 0.12 mol) in DCM (700 mL) at 0C was added N-bromosuccinimide (44.64 g, 0.25 mol) portion-wise. The reaction was stirred for 2 hrs. The reaction was washed with sat Na2CO3 (3 x 200 mL), dried over Mg504, filtered and concentrated in vacuo before purification by column chromatography (20% EtOAc/heptane) to give the title compound as a yellow solid (15.9 g, 53%). LCMS: m/z 252/254/256 [M+H].

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 5049-61-6.

Reference:
Patent; CHROMA THERAPEUTICS LTD; DAVIES, Stephen John; PINTAT, Stephane; NORTH, Carl Leslie; MOFFAT, David Festus Charles; WO2014/1802; (2014); 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. 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., 1458-18-0

Under an argon atmosphere,Isoamyl nitrite (26.6 mL, 200 mmol) was added to a THF solution of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate (4.44 g, 20.0 mmol) in THF (30 mL). The reaction mixture was stirred at 80 C. for 17 hours. After standing to cool, the low boiling point compound was distilled off to obtain a crude product. This crude product was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 100/0 to 90/10) to obtain methyl 5,6-dichloropyrazine-2-carboxylate (2.29 g, 55% ) As a white solid.

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; TOSOH CORPORATION; SAGAMI CHEMICAL RESEARCH INSTITUTE; AIHARA, HIDENORI; SHONO, TOMOHIRO; (23 pag.)JP2015/140319; (2015); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, 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. 4858-85-9

To a 1.0 M solution of LiHMDS in toluene (14.8 mL, 14.8 mmol) under nitrogen at 0 C was added 2,3-dichloropyrazine (0.699 mL, 6.71 mmol) and ethyl acetate (0.725 mL, 7.38 mmol). The mixture was stirred overnight for 18 hours, allowing the ice bath to warm to room temperature. The mixture was poured into saturated ammonium chloride (100 mL), and extracted with diethyl ether (3×100 mL). The combined ether extracts were washed with brine, dried (sodium sulphate) and evaporated. The residue was chromatographed (40 g silica cartridge, 0-25% ethyl acetate/petroleum benzine 40-60 C) to give the title compound (199) (0.414 g, 31 % yield) as a pale yellow oil; 1 H NMR (400 MHz, CDCI3) delta 8.46 (d, J = 2.5 Hz, 1 H), 8.31 (d, J = 2.5 Hz, 1 H), 4.22 (q, J = 7.1 Hz, 2H), 4.03 (s, 2H), 1.27 (t, J = 7.1 Hz, 3H). LCMS Method C: rt 5.16 min.

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 4858-85-9.

Reference:
Patent; CANCER THERAPEUTICS CRC PTY LTD; DEVLIN, Mark Graeme; STREET, Ian Philip; TONG, Warwick Bonner; WO2014/27199; (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. 98-97-5, name is Pyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., 98-97-5

? Charged MeOH (8.8 L) and OT-1 (1758 g) at RT. (0129) ? Charged H2S04 (69.5 g) in one portion (21-22 C exotherm). Heated to (60-65 C) and stirred at 55-65 C for 19 hours. (0130) 19 h, 96.0% OT-2 and 4.0% OT-1 by HPLC (0131) ? Reaction was cooled to 15/30 C. No precipitate formed. (0132) ? NaHC03 (180 g) was charged in lots. The solution bubbled slightly and quickly went from yellow to pink. The mixture was stirred for 5 min at 15/30 C. (0133) ? The mixture was then concentrated to 1.5-2.5 vol at (0134) ? Charged NaCl (.700 g) in water (2.5 vol). Upon stirring, solution became clear. (0135) ? Stirred for 15 min at 15/30 C. After stirring, the aqueous layer became slightly cloudy. The solids were filtered off and the layers were separated. (0136) ? The aqueous layer was extracted with DCM (3×2 vol.). TLC indicated that extraction was complete after 3rd extraction. (0137) ? Organic layers were dried over anhydrous Na2S04 (.4g/g SM) . (0138) ? Concentrated to 1.5-2.5 vol under vacuum at (0139) ? Charged heptanes (8 vol) over a minimum of 30 min. Pale white slurry. Let stir overnight. ? Stirred at -5/- 15 C for a minimum of 1 hr. Solids were filtered off and rinsed with cold heptanes (0140) ? (2×1 vol.) Pulled solids dry on filter for 10 min. Dried in vacuum oven at (0141) Color changed, but no degradation was observed . (0142) Output material: ST-601 (0143) Lot No.: 2463-24- 1 (0144) Appearance: light Brown Solids (0145) Yield: 1721 g (91.0%) (0146) HPLC purity: 98.9% (0147) 1 NMR- Conforms to structure

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; ST IP HOLDING AG; FRAMROZE, Bomi P.; (65 pag.)WO2016/207914; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6270-63-9, 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. 6270-63-9 name is Pyrazin-2(1H)-one, 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.

Using the same procedure described in example 1 using 1-(4-amino-3-fluoro-phenyl)-1H-pyrazin-2-one (prepared from 2-fluoro-4-iodoaniline by reaction with 1H-pyrazin-2-one, Cu(I)I, N,N’-dimethylethylenediamine and cesium carbonate in dioxane at 120 C.), the title compound was obtained as a white solid (15 mg). MS: 508.0 (M+H)+

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Pyrazin-2(1H)-one, and friends who are interested can also refer to it.

Reference:
Patent; Boehringer, Markus; Zbinden, Katrin Groebke; Haap, Wolfgang; Hilpert, Hans; Panday, Narendra; Ricklin, Fabienne; US2007/15812; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

19745-07-4, 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. 19745-07-4, name is 2,5-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Description 6 1,1-Dimethylethyl 7-[(5-ch loro-2-pyrazi nyl)oxy]-1,2,4,5-tetrahyd ro-3H-3-benzazepi ne- 3-carboxylate (D6); 1,1-Dimethylethyl 7-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (182 mg, 0.69 mmol: obtainable by the process described in Description 3 from WO 02/40471) was dissolved in dry dimethylformamide (3 ml), cooled in an ice bath and treated with sodium hydride (60 percent in mineral oil, 29 mg, 0.72 mmol). The mixture was allowed to warm to room temperature over 1 hour. A solution of 2,5-dichloropyrazine (D5) (112 mg, 0.76 mmol) in dimethylformamide was added and the mixture stirred at room temperature for 2 hours and left to stand overnight under argon. The mixture was diluted with water and extracted with ethyl acetate (x 2). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated. The residue was purified by Biotage column chromatography, eluting with 1: 4 ethyl acetate: pentane to afford the title compound (208 mg). MS (ES+) m/e 376 [M+H]+.

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

Reference:
Patent; GLAXO GROUP LIMITED; WO2005/123723; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 5780-66-5, name is Pyrazine-2-carbaldehyde, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 5780-66-5

Intermediate 85 Ethyl 1-phenyl-3- [ (2-pyrazinylmethyl) amino]-1 H-pyrazole-4-carboxylate To ethyl 3-amino-1-phenyl-1H-pyrazole-4-carboxylate (250 mg, 1.08 mmol) was added DCM (6 mL), pyrazine-2-carboxaldehyde (233 mg, 2.16 mmol), acetic acid (0.18 mL, 3.24 mmol) and sodium triacetoxyborohydride (0.46 g, 2.16 mmol). The reaction was stirred overnight at room temperature, partitioned between DCM and water, passed through a hydrophobic frit and the organic layer concentrated. Purified by MDAP HPLC to give the title compound. MS calcd for (C17H17N5O2+H)+ : 324 MS found (electrospray) : (M+H) + = 324

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, 5780-66-5, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; WO2005/92863; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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. 5521-58-4

Intermediate 19: 3-[(3S)-1-Methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)-5-phenylmethoxy-benzamide 1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.979 mL, 7.4 mmol) was added to a solution of 3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-phenylmethoxy-benzoic acid (Intermediate 20) (2.1 g, 6.2 mmol) in DCM (50 mL) and stirred at ambient temperature for 50 minutes. 5-Methylpyrazin-2-amine (CAS no. 5521-58-4) (1.35 g, 12.4 mmol) and pyridine (1.0 mL, 12 mmol) were added and the reaction stirred for a further 3 hours. The solvent was evaporated under reduced pressure and the residue taken up in ethyl acetate (50 mL), washed with water (2*10 mL), brine (10 mL), dried (MgSO4) and filtered. Evaporation under reduced pressure gave crude product which was purified by flash chromatography on silica, eluding with a gradient of 0-100% ethyl acetate in isohexane. This crystallized to afford the product (449 mg, 17%). To the filtrate was added saturated sodium bicarbonate (20 mL) and the mixture extracted with 2:1 ethyl acetate:DCM (3*45 mL), the organics were washed with brine (10 mL), dried (MgSO4), filtered and evaporated under reduced pressure to give further product (937 mg, 35%). 1H NMR delta (300 MHz, CDCl3) 2.09-2.24 (m, 1H), 2.53-2.66 (m, 4H), 2.94 (s, 3H), 3.33-3.57 (m, 2H), 4.89 (t, 1H), 5.10 (s, 2H), 6.91 (s, 1H), 7.15-7.20 (m, 2H), 7.30-7.48 (m, 5H), 8.13 (s, 1H), 8.40 (s, 1H), 9.54 (s, 1H); m/z 433 (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 5521-58-4, its application will become more common.

Reference:
Patent; AstraZeneca AB; US2008/171734; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5049-61-6, 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. 5049-61-6 name is Pyrazin-2-amine, 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 2-aminopyrazine 4 (3.81 g, 40.1 mmol) in DMSO (80 mL) and water (2 mL) was stirred at 0 C for 10 min. NBS (16.4 g, 92.2 mmol) was added portionwise to the solution over 50 min, keeping the temperature below 15 C. The reaction mixture was warmed to rt and stirred for 16 h. The solution was poured into ice-water (250 mL) and stirred. The orange solid was collected by filtration and dried. The filtrate was extracted with ethyl acetate (200 mL). The organic layer was washed with 5% aqueous sodium carbonate (50 mL) and water (50 mL), then dried, filtered and concentrated. The combined material was recrystallised from water (200 mL) to give 5 (7.80 g, 77%) as a brown solid. (Found: C, 19.33; H, 1.10; N, 16.68; C4H3N3Br2 requires C, 19.00; H, 1.20; N, 16.62%); deltaH (250 MHz; CDCl3) 5.08 (2H, br s, NH2), 8.07 (1H, s, 6-H); deltaC (125 MHz; CDCl3) 123.7, 123.9, 143.2, 151.9; LC-MS (15 min) m/z 256, 254, 252 (MH+); HPLC tR 4.45 min; purity 98%; (HRMS found: MH+ m/z 251.8776; requires 251.8766).

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

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

Some common heterocyclic compound, 113305-94-5, name is 5-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. 113305-94-5

Svnthesis 1-1 -B5-(4-(4~Methoxybenzylamino)-5-nitropyridin-2-ylamino)pyrazine-2-carbonitrile A mixture of palladium (II) acetate (38 mg, 0.17 mmol) and (+/-)-2,2″- bis(diphenylphosphino)-1 ,1″-binaphthalene (318 mg, 0.51 mmol) a mixture of toluene and DMF (1 :1, 10 ml_) was degassed under a stream of nitrogen gas with stirring for 30 minutes. After addition of 2-amino-5-cyanopyrazine (245 mg, 2.04 mmol), sodium tert- butoxide (196 mg, 2.04 mmol) and N-(4-methoxybenzyl)-2-bromo-5-nitropyridin-4-amine (575 mg, 1.70 mmol), the mixture was degassed for a further 5 minutes and then heated at 140C for 30 minutes in a microwave reactor. Upon cooling, the mixture was diluted with methanol and isolated by SPE using 3 x 2.5 g MP-TsOH cartridges, washing with methanol and then eluting with 2 M ammonia in methanol. The basic fractions were concentrated in vacuo to give the title compound (470 mg, 1.25 mmol, 73%) which was used without further purification. LCMS (2) Rt = 2.18min; m/z (ESI-) 376 (M-H); (ESI+) 378 (MH+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 113305-94-5, its application will become more common.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; WO2009/103966; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem