Month: June 2021

These common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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. HPLC of Formula: C6H6N2O2

5-Methylpyrazin-2-carboxylic acid (13.81 g, 0.1 mol), tert-butanol (95 mL, 1 mol), triethylamine (27.9 mL, 0.2 mol) and diphenylphosphoryl azide (30.27 g, 0.11 mol) were mixed in 300 mL toluene, heated to reflux and reacted for 8 hours, and chromatographed on a silica gel column (petroleum ether – petroleum ether:ethyl acetate=20:1) to obtain a light yellow solid 15.2 g, at a yield of 72.7%.

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

Reference:
Patent; KBP Biosciences Co., Ltd.; ZHANG, Yan; ZHANG, Min; LO, HoYin; (52 pag.)EP2781508; (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. 28643-16-5, name is Methyl 3-amino-5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: Methyl 3-amino-5-chloropyrazine-2-carboxylate

a) 3-Amino-5-vinyl-pyrazine-2-carboxylic acid methyl ester To a mixture of 3-amino-5-chloro-pyrazine-2-carboxylic acid methyl ester (GB 1248146, 161 mg 0.86 mmol), tributyl(vinyl)tin (0.352 ml, 1.204 mmol) and lithium chloride (102 mg, 2.498 mmol) in DMF (4 ml) was added PdCI2(PPh3)2 (30.2 mg, 0.043 mmol) and the mixture was heated to 85 C for 2.5 h. After cooling to room temperature water was added and the mixture was extracted with EtOAc, the combined organic layers were washed with water and half saturated aq. NaCI, dried with Na2S04 and evaporated. The residue was purified by chromatography on silica gel (cyclohexane to cyclohexane/EtOAc 1 :9) to provide the title compound as yellow solid. HPLC: RtH4= 0.71 min; ESIMS [M+H]+ = 179.9; 1H-NMR (600 MHz, DMSO-c 6): delta 8.04 (s, 1 H), 7.35 (br. s, 1 H), 6.75 (dd, 1 H), 6.38 (d, 1 H), 5.70 (d, 1 H), 3.84 (s, 3H).

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; NOVARTIS AG; LUEOEND, Rainer Martin; MACHAUER, Rainer; RUEEGER, Heinrich; VEENSTRA, Siem Jacob; WO2013/27188; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 91476-80-1, 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. 91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To (3R)-tert-butyl 3-(2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-4-iodo-3-(1-(4- methoxybenzyl)-1H-tetrazol-5-yl)phenylsulfonamido)pyrrolidine-1-carboxylate (REFERENCE EXAMPLE 5) (120 mg, 0.125 mmol) and 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (30.8 mg, 0.250 mmol), Cs2CO3 (122 mg, 0.375 mmol), and RAC-BINAP-Pd-G3 precatalyst (25 mg, 0.025 mmol) were added to DME (2.5 mL) at RT and the mixture was degassed for 10 min under nitrogen, stirred at 80 C overnight. The mixture was diluted with water (50 mL), extracted with EtOAc (2 x 50 mL). The combined organic phases were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a gradient of 0 – 25% heptane/ethanol over 20 min to give the title product. LC/MS [M+H]: 955.

The synthetic route of 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DONG, Shuzhi; SCOTT, Jack, D.; TANG, Haiqun; ZHAO, Zhiqiang; YANG, Dexi; XIAO, Li; GU, Xin; JIANG, Jinlong; (85 pag.)WO2019/135920; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 33332-25-1, A common heterocyclic compound, 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, molecular formula is C6H5ClN2O2, 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 26 2-Ethyl-2-{[5-morpholin-4-yl-6-(2,2,2-trifluoro-ethoxy)-pyrazine-2-carbonyl]-amino}-butyric acid methyl ester a) 5-Morpholin-4-yl-pyrazine-2-carboxylic acid methyl ester; A mixture of 4.9 g (28 mmol) 5-chloro-pyrazine-2-carboxylic acid methyl ester (commercially available), 3.2 g (37 mmol) morpholine and 7.37 g (73 mmol) NEt3 in 50 mL dioxane was heated to 45 C. for 16 h. Water and NaCl aq. was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with NaCl aq., dried with MgSO4, filtered and evaporated. The residue was recrystallized from ethyl acetate to yield 5.65 g (89%) of the title compound as white solid. m/z (ES+): 224.3 (M+H).

The synthetic route of 33332-25-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dietz, Michel; Gruener, Sabine; Hebeisen, Paul; Meyer Reigner, Sylvie C.; Nettekoven, Matthias; Puellmann, Bernd; Roever, Stephan; Ullmer, Christoph; US2008/85905; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 32974-92-8,Some common heterocyclic compound, 32974-92-8, name is 1-(3-Ethylpyrazin-2-yl)ethanone, molecular formula is C8H10N2O, 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.

(1) Dissolving 10 mmol of 2-acetyl-3-ethylpyrazine in 20 mL of methanol,Stir at 60 C for 15 min,Will then20 mL, 10 mmol of thiosemicarbazide in methanol was added dropwise to the above solution.After refluxing at 60 C for 12 h,After cooling to room temperature, pour into the beaker and evaporate.The pale yellow crystal obtained above was filtered and washed with methanol three times.Get ligand (L1);

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-(3-Ethylpyrazin-2-yl)ethanone, its application will become more common.

Reference:
Patent; Guangxi Normal University; Yang Feng; Yu Ping; Wang Jun; Liang Hong; (14 pag.)CN108912149; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 13134-31-1, 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. 13134-31-1, name is 2,3-Diaminopyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 7 2-(2-Methoxy-4-methanesulfonylamino-phenyl)-imidazo[4,5-b]-pyrazine This compound was prepared analogous to Example 2 from 2,3-diamino-pyrazine and 2-methoxy-4-methanesulfonylaminobenzoic acid. M.p. 263-265 C.

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, 2,3-Diaminopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Dr. Karl Thomae GmbH; US4656171; (1987); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1174321-06-2,Some common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H4F2N2O2, 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 Example 130E (0.05 g, 0.146 mmol), 5-(difluoromethyl)pyrazine-2- carboxylic acid (0.029 g, 0.168 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.102 mL, 0.583 mmol) in N,N-dimethylformamide (1.5 mL) was treated with 2-(3H-[l ,2,3]triazolo[4,5- Z?]pyridin-3-yl)- l ,l ,3,3-tetramethylisouronium hexafluorophosphate(V) (0.083 g, 0.219 mmol), and the reaction was stirred at ambient temperature for 30 minutes. Volatiles were removed under high vacuum, and the residue was purified by HPLC (10-95% acetonitrile in 0.1% trifluoroacetic acid/water on Phenomenex CI 8 5 mupiiota (250 mm x 21.2 mm) column at a flowrate of 25 mL/minute) to give 43 mg of the title compound as a solid. JH NMR (400 MHz, DMSO- ) delta ppm 9.19 (d, J = 1.4 Hz, 1H), 8.94 (d, J = 1.2 Hz, 1H), 8.03 (s, 1H), 7.45 (t, J = 8.9 Hz, 1H), 7.28 (d, J = 6.0 Hz, 1H), 7.16 (m, 1H), 7.07 6.98 (m, 1H), 6.80 (ddd, J = 9.0, 2.9, 1.2 Hz, 1H), 5.13 (d, J = 4.4 Hz, 1H), 4.44 (s, 2H), 4.08 (ddd, J = 9.9, 5.4, 3.1 Hz, 1H), 2.39 (ddd, J = 12.6, 9.5, 2.5 Hz, 1H), 2.13 2.01 (m, 2H), 1.95 (q, J = 4.8, 2.6 Hz, 1H), 1.94 1.76 (m, 6H); MS (ESI+) m/z 499.1 (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 5-(Difluoromethyl)pyrazine-2-carboxylic acid, its application will become more common.

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

Application of 28643-16-5,Some common heterocyclic compound, 28643-16-5, name is Methyl 3-amino-5-chloropyrazine-2-carboxylate, molecular formula is C6H6ClN3O2, 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-Amino-5-((Z)-2-ethoxy-vinyl)-pyrazine-2-carboxylic acid methyl ester A mixture of 3-amino-5-chloro-pyrazine-2-carboxylic acid methyl ester [28643-16-5] (2 g, 10.66 mmol), lithium chloride (1.582 g, 37.3 mmol), Pd(PPh3)2CI2 (0.748 g, 1.066 mmol) and tributyl- ((Z)-2-ethoxy-vinyl)-stannane (6.42 ml, 19.19 mmol) in DMF (104 ml) under argon was heated at 80 C bath temperature for 1.5 h. A saturated, aq. NH4CI was added and the mixture was extracted with MTBE, then once with EtOAc/THF 3/1. The combined organic layer was washed with brine, dried with Na2S04, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane to cyclohexane/EtOAc 1 :9) to provide the title compound as yellow oil (1.96 g). HPLC: RtH2= 0.69 min; ESIMS [M+H]+ = 225.1 ; 1H-NMR (400 MHz, DMSO-c 6): delta 8.42 (s, 1 H), 7.18 (br. s, 2H), 6.88 (d, 1 H), 5.23 (d, 1 H), 4.15 (q, 2H), 3.82 (s, 3H), 1.32 (t, 3H).

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-chloropyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; NOVARTIS AG; LUEOEND, Rainer Martin; MACHAUER, Rainer; RUEEGER, Heinrich; VEENSTRA, Siem Jacob; WO2013/27188; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 19745-07-4,Some common heterocyclic compound, 19745-07-4, name is 2,5-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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.

3-CYCLOBUTYL-2, 3,4, 5-TETRAHYDRO-1H-BENZO [d] azepin-7-ol (E3) (184 mg, 0.85 MMOL) was dissolved in dry dimethylformamide (3 ml), cooled to 0 °C and treated with sodium hydride (60 percent in mineral oil, 36 mg, 0.89 MMOL). The mixture was allowed to warm to room temperature over 30 minutes. A solution of 2, 5-dichloropyrazine (D47) (139 mg, 0.94 MMOL) in dry dimethylformamide (1 ml) was added and the mixture stirred at room temperature for 5 hours. The mixture was applied to a SCX column and washed with methanol then a mixture of. 880 ammonia/methanol (1: 9). The basic fractions were combined and concentrated in vacuo to afford the title compound (268 mg); MS (ES+) m/e 330 [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 2,5-Dichloropyrazine, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2004/56369; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 136927-64-5, name is 1-Chloropyrrolo[1,2-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 136927-64-5, Computed Properties of C7H5ClN2

4-Bromo-3-methylphenol (0.26 g, 1.4 mmol), 1-chloropyrrolo[1,2- a]pyrazine (0.16 g, 1.1 mmol), and cesium carbonate (0.69 g, 2.14 mmol) were combined in dimethyl sulfoxide (5 mL), and the reaction mixture was degassed withnitrogen for 5 minutes. After it had been heated to 120 00 for 3 hours, the reaction mixture was cooled to room temperature and allowed to stand for 12 hours, whereupon it was diluted with ethyl acetate, then filtered through diatomaceous earth. The filter pad was rinsed with ethyl acetate, and the combined filtrates were washed with 1:1 water I saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, andconcentrated in vacuo. Purification using silica gel chromatography afforded the product (344 mg) containing some impurities (-60% purity). This material was used without further purification. LCMS m/z 303.0 [M+H].

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; PFIZER INC.; GRAY, David Lawrence Firman; DAVOREN, Jennifer Elizabeth; DOUNAY, Amy Beth; EFREMOV, Ivan Viktorovich; MENTE, Scot Richard; SUBRAMANYAM, Chakrapani; WO2015/166370; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem