Category: Pyrazines

Synthetic Route of 98-97-5, The chemical industry reduces the impact on the environment during synthesis 98-97-5, name is Pyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

Step 1 (esterification of pyrazine-2-carboxylic acid to yield methyl-pyrazine-2-carboxylate): To a 1L single-neck round-bottomed flask fitted with condenser and drying tube filled with silica gel was charged methanol (400 mL) with agitation at room temperature. Pyrazine-2-carboxylic acid (50.00 g, 402.90 mmol) was charged to the flask in one portion and the resulting slurry was vigorously stirred. Conc. sulfuric acid (0.25 mL) was charged to the slurry. The slurry was heated to reflux temperature and stirred at this temperature for 2 days. The resulting pale yellow solution was allowed to cool to room temperature. This process takes 90 minutes. Solid sodium bicarbonate (4.00 g, 47.62 mmol) was added to the solution in one portion and the slurry was stirred vigorously for 30 minutes. The suspension was filtered and the filtrate was transferred to a 2L single-neck round-bottomed flask and concentrated to about half volume in vacuo a 35 C. Toluene (1200 mL) was added to the methanol solution and a Dean-Stark trap fitted with drying tube was attached. The solution was heated at atmospheric pressure (external oil bath a120 C.) and the first 300 mL solvent fraction was run off and discarded. The Dean-Stark trap was removed and the reaction solution was concentrated in vacuo a45 C. to a volume of 300 mL. The organic phase containing the desired methyl-pyrazine-2-carboxylate was filtered to remove solid particulates and used directly in the next step as a solution in toluene (a small analytical sample was removed and concentrated in vacuo a 35 C. to yield a pale brown solid, m.p. 60-61 C., structure confirmed by 1H NMR and 13C NMR).

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, Pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Patrick Prendergast; US2004/53989; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 75907-74-3, These common heterocyclic compound, 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, 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.

(4) In a round bottom flask, add formula (4) (1.0 equiv), using DCM as solvent.Add phosphorus tribromide (1.0-2.0 equiv) at 0 C, stir the reaction at 25 C for 1 h, TLC monitoring formula (4) disappeared, after the reaction was completed, water was added, dichloromethane was extracted, and the organic layer was collected.Drying and concentrating gave the compound of the formula (5) as a white solid.

Statistics shows that (3,5,6-Trimethylpyrazin-2-yl)methanol is playing an increasingly important role. we look forward to future research findings about 75907-74-3.

Reference:
Patent; Chengdu University; Zou Liang; Zhang Jinming; Li Junlong; Liu Xiaowei; Li Wei; Shen Xudong; Dai Liping; Zhuo Hongyi; (13 pag.)CN108440512; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6905-47-1, name is 2-Amino-6-methoxypyrazine, 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. Quality Control of 2-Amino-6-methoxypyrazine

The 3-amino-2-chloro-5-methoxypyrazine used as a starting material were prepared asfollows :-N-Chlorosuccinimide (1.7 g) was added portionwise to a solution of 2-amino-6-methoxypyrazine (S K Vohra et al, J. Org. Chem., 1979,44,1128; 1.6 g) in chloroform(26 ml) and the resultant mixture was stirred at ambient temperature for 3 hours. Silica gel(10 g) was added and the solvents were evaporated. The residue was purified by columnchromatography on silica gel using methylene chloride as eluent. There were thus obtained inturn :- 2-amino-3,5-dichloro-6-methoxypyrazine (0.253 g); NMR Spectrum: (CDC13) 3.95(s, 3H), 4.83 (m, 2H); Mass Spectrum: M+ET1″ 194; a sample of 3-amino-2-chloro-5-methoxypyrazine that was contaminated with succinimide and 5-amino-2-chloro-3-methoxypyrazine (0.339 g); NMR Spectrum: (CDC13) 3.95 (s, 3H), 4.27 (m, 2H), 7.32(s, 1H); Mass Spectrum: M+H* 160. The fraction containing 3-amino-2-chloro-5-methoxypyrazine was purified further by column chromatography on silica gel eluting with a10:1 mixture of petroleum ether (b.p. 40-60C) and ethyl acetate. There was thus obtainedpurified material (0.94 g); NMR Spectrum: (CDC13) 3.87 (s, 3H), 4.82 (m, 2H), 7.36 (s, 1H);Mass Spectrum: M+H+ 160.

The synthetic route of 6905-47-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/108711; (2004); 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. 4774-14-5, name is 2,6-Dichloropyrazine, A new synthetic method of this compound is introduced below., category: Pyrazines

-Chloro-N-phenylpyrazin^-amine. 2,6-Dichloropyrazine (510 mg,3.4 mmol), palladium acetate (75 mg, 0.33 mmol), 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (405 mg, 0.7 mmol), potassium carbonate (4.6 g, 33.3 mmol), and aniline (0.3 mL, 3.3 mmol) were suspended in anhydrous dioxane (23 mL). The resulting mixture was degassed with nitrogen for 5 minutes and stirred at 9O0C for one hour. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (3 x 50 mL), and the organic layers were combined and dried over magnesium sulfate. After filtration, the solvent was removed in vacuo. The residue was purified by silica gel chromatography (0-60% ethyl acetate in hexanes) to give the title compound as a white solid (88 mg, 0.43 mmol, 13% yield); 1H NMR (DMSO-^6) delta 9.86 (s, IH), 8.17 (s, IH), 7.98 (s, IH), 7.63 (d, J= 10.0 Hz, 2H), 7.35 (t, J= 7.2 Hz, 2H), 7.03 (t, J= 6.8 Hz, IH); MS (ESI) MS (ESI) m/z 206.0 [M+ 1]+.

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SIGNAL PHARMACEUTICALS, LLC; WO2009/89042; (2009); 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, Product Details of 486460-21-3

In 100 mL of tetrahydrofuran,4.11 g (41 mmol) of triethylamine was added,6.60g (20mmol) of compound IV and4.81 g (25 mmol) of 3-trifluoromethyl-1,2,4-triazolo[4,3-a]pyrazine was refluxed for 1 hour.TLC monitors the progress of the reaction,After the reaction is completed,Concentrated under reduced pressure,Purified by column chromatography,That is, the product sitagliptin 7.90g (19.4mmol),The yield was 97%, HPLC purity = 99.88%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Shenzhen The Second People Hospital; Yan Dewen; Tan Hui; Zuo Xin; (8 pag.)CN109761988; (2019); A;,
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. 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Formula: C6H6BrN3O2

Methyl 3-amino-6-bromopyrazine-2-carboxylate (10 g,1 eq) was suspended in concentrated H2SO4 (40 mL), andthen, NaNO2 (5.96 g, 2 eq) was added in batches at -5 to0 C, after which the reaction was stirred at 25 C for 2 huntil the solid was all dissolved. Then, the reaction solutionwas poured into ice water (400 mL) and vigorously stirredfor 1.5 h. Afterward, the solution was extracted with ethylacetate (3 9 50 mL). The organic layer was combined andwashed with water (3 9 30 mL). Then, it was dried withanhydrous Na2SO4 for 5 h and filtered to remove the dryingagent. The ethyl acetate was removed by distillation under reduced pressure to obtain methyl 3-hydroxy-6-bromopyrazine-2-carboxylate (9.3 g, 92.7%) (TLC,EA:MeOH = 1:1, v/v, Rf = 0.77).Methyl 3-hydroxy-6-bromopyrazine-2-carboxylate(4)Yield: 92.7%, gray solid, m.p.: 120-122 C (Lit.120.5-121.5 C) (Caldwell et al. 2012). 1H-NMR(400 MHz, DMSO-d6): d 8.40 (s, 1H), 3.85 (s, 3H). 13CNMR(101 MHz, DMSO-d6): d 163.20, 157.11, 143.89,134.81, 122.06, 52.43. MS (EI): m/z = 233.0 (M?, Br79,40), 235.0 (M?, Br81, 40), 202.0 (M?, -OCH3, Br79, 45),204.0 (M?, -OCH3, Br81, 25), 174.0 (M?, -COOCH3,Br79, 100), 176.0 (M?, -COOCH3, Br79, 60).

According to the analysis of related databases, 6966-01-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Liu, Feng-Liang; Li, Cui-Qin; Xiang, Hao-Yue; Feng, Si; Chemical Papers; vol. 71; 11; (2017); p. 2153 – 2158;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 63744-22-9, A common heterocyclic compound, 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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.

Example 10-1 :Preparation of 6,8-dibromo-3-iodo-imidazo[1 ,2-a]pyrazine To a stirred solution of intermediate example 1-1 (8.7 g g, 31.4 mmol) in DMF (210 mL) was added NIS (7.42 g, 33 mmol, 1.05 eq) in one portion at rt. After 18 h stirring at 60 C, the solvent was removed in vaccuo and the residue was taken up in DCM and washed with water and saturated sodium thiosulfate solution. The organic phase was dried over sodium sulphate, filtered and the solvent was evaporated to yield 9.46 g (74.8 %) 6,8-dibromo-3-iodo-imidazo[1,2-a]pyrazine: 1H-NMR (300 MHz, CDCb): delta = 8.22 (1H, s), 7.91 (1H, s) ppm.

The synthetic route of 63744-22-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80230; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 33332-28-4, 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. 33332-28-4 name is 2-Amino-6-chloropyrazine, 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.

EXAMPLE 7 N-(6-Chloro-pyrazin-2-yl)-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide A mixture of 5.1 g (20 mmols) of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide, 3.0 g (23 mmols) of 2-amino-6-chloropyrazine and 400 ml of xylene was refluxed for 12 hours in a nitrogen atmosphere. The methanol formed by the reaction was removed with the aid of a 4 A molecular sieve arranged in a Soxhlet attachment. After cooling, the reaction mixture was concentrated by evaporation, and the residue was purified by chromatography on a silicagel column, yielding 2.3 g (33percent of theory) of N-(6-chloro-pyrazin-2-yl)-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide. Melting point: 234¡ã-235¡ã C. (from ethanol). C13 H9 ClN4 O4 S (352.76): Calc.: C–44.26percent; H–2.57percent; N–15.88percent; Cl–10.05percent; S–9.09percent. Found: C–44.02percent; H–2.65percent; N–15.92percent; Cl–10.10percent; S–9.24percent.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Dr. Karl Thomae Gesellschaft mit beschrankter Haftung; US4533664; (1985); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 22047-25-2, The chemical industry reduces the impact on the environment during synthesis 22047-25-2, name is Acetylpyrazine, I believe this compound will play a more active role in future production and life.

A solution of 5.4 g (40 mmol) 1-Pyrazin-2yl-ethanone in 21 ml HBr (33%) and 7 ml methanol was treated with 2.05 ml (40 mmol) bromine and heated to 60 C. for 7 h.The precipitate was filtered off, washed with ethyl acetate/diethyl ether 1/1 and dried to obtain 8.3 g (55%) of the title compound as grey solid. 1-H-NMR (400 MHz, DMSO-d6) delta=8.78 (d, J=2 Hz, 1H, H-5), 8.66 ((d, J=2 Hz, 1H, H-6), 5.01 (s, 2H, CH2), 2.75 (s, 3H, CH3). MS (m/e): 215.0 (M+H, 100%).

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, Acetylpyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Mattei, Patrizio; Neidhart, Werner; Nettekoven, Matthias Heinrich; Pflieger, Philippe; Taylor, Sven; US2003/225141; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4744-50-7, These common heterocyclic compound, 4744-50-7, name is 2,3-Pyrazinecarboxylic anhydride, 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 3-(m-methylbenzoyl)-pyrazine-2-carboxylic acid The Grignard reagent from 8.5 g (50 mmol) 3-bromotoluene and 1.2 g magnesium in 50 ml ether was added dropwise at 0-10 C. to a solution of 7.5 g (50 mmol) pyrazine-2,3-dicarboxylic acid anhydride in 100 ml THF and after completed addition, the solution that formed was stirred for 4 hours at room temperature. 500 ml cold, saturated NH4 Cl solution was then added, it was extracted with ethyl acetate and the organic phase was dried, concentrated by evaporation and purified as in example 1a and 2a. Yield 4 g (32% of theoretical yield).

Statistics shows that 2,3-Pyrazinecarboxylic anhydride is playing an increasingly important role. we look forward to future research findings about 4744-50-7.

Reference:
Patent; Boehringer Mannheim GmbH; US5512564; (1996); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem