Month: April 2021

Application of 312736-49-5, 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. 312736-49-5 name is 3,5-Dichloropyrazine-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.

To a solution of 3,5-dichloropyrazine-2-carboxylic acid (0.304 g, 1.58 mmol) in MeOH (5 mL) and diethyl ether (5 mL) at room temperature was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 4.00 mL, 8.00 mmol). The reaction mixture was stirred at RT for 30 min and concentrated. Purification by flash column chromatography on silica gel (5% to 20% EtOAc in hexanes) gave methyl 3,5- dichloropyrazine-2-carboxylate (0.312 g, 1.51 mmol, 96%o yield) as a white solid. LC/MS (ESf) m/z = 207.0 (M+H) +

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dichloropyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; AMGEN INC.; MINATTI, Ana Elena; LOW, Jonathan, D.; ALLEN, Jennifer, R.; AMEGADZIE, Albert; BROWN, James; FROHN, Michael, J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul, E.; LOPEZ, Patricia; MA, Vu Van; NISHIMURA, Nobuko; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert, M.; SHAM, Kelvin; SMITH, Adrian, L.; WHITE, Ryan; XUE, Qiufen; WO2014/138484; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 38557-72-1, A common heterocyclic compound, 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, molecular formula is C6H7ClN2, 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.

[0450] Preparation Example 104: Preparation of (3,5-dimethylpyrazin-2-yl)piperazine hydrochloride[0451][0452] Under a nitrogen stream, to a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium(II) acetate (225 mg), 2-(dicyclohexylphosphino)-2?,4?,6?-triisopropyl-1,1?-biphenyl (953 mg) and sodium tert-butoxide(2.7 g) was added toluene (40 mL), and the mixture was stirred with heating under reflux for 8 hr. After cooling,the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent wasevaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g). The obtained (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL)was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added ethyl acetate(100 mL), and the precipitate was collected by filtration to give the title compound (3.3 g).

The synthetic route of 38557-72-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; MAEDA, Kazuhiro; ENDOH, Jun-ichi; TARAO, Akiko; TASHIRO, Kaoru; ISHIBUCHI, Seigo; HIKAWA, Hidemasa; EP2565182; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, 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 87486-34-8, SDS of cas: 87486-34-8

A solution of tert-butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate (2d, 1.7 g, 5.7 mmol, 1 equiv.), 3,5-dibromo-1-methylpyrazin-2(1H)-one (2e, 1.8 g, 6.8 mmol, 1.2 equiv.)and N,N-diisopropylethylamine (1.48 mL, 8.5 mmol, 1.5 equiv.) in N,N-dimethylacetamide (5 mL) was stirred in a sealed vial at 105 C for 30 h. The reaction was cooled to room temperature and EtOAc (20 mL) was then added. The solid precipitate was filtered and dried on high vacuum overnight to provide tert-butyl 4-(4-((6-bromo-4-methyl-3-oxo-3 ,4- dihydropyrazin-2-yl)amino)benzoyl)piperazine- 1 -carboxylate 2f. The product was carriedonto the next step without further purification.

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; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael S.; DOBROVOLSKY, Dennis; HUANG, Hai-Tsang; (152 pag.)WO2018/98275; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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.

To a solution of 3-chloropyrazine-2-carbonitrile 14 (4.60 g,32.96 mmol) in EtOH (120 mL) was added NaSH (3.94 g,42.79mmol), and themixture was stirred at roomtemperature for 3 h (TLC monitoring). EtOH was evaporated under reduced pressure,and the residue was dissolved in H2O and 2 M HCl was carefully added to neutralize the suspension. After evaporation of the solvent, the residue was dissolved in acetone (48 mL) and ClCH2CN (2.29 mL, 32.96 mmol), K2CO3 (4.55 g, 32.96 mmol), and a catalytic amount of KI were added. The resulting mixture was stirred at room temperature for 3 h, and then the resulting residue was separated by filtration and washed with acetone (3 30 mL). The filtrate was evaporated under reduced pressure, the resulting residue was dissolved in THF (240 mL), piperidine (3.26 mL, 32.96 mmol) was added, and the mixture was stirred at reflux for 5 h. After cooling, the solution was concentrated to dryness, and the residual material was purified by column chromatography (eluent: 100% dichloromethane) to give 7-aminothieno[2,3-b]pyrazine-6-carbonitrile 1d as a yellow powder (3.66 g, 63%); Rf ? 0.18 (dichloromethane); mp 205e207 C (lit. [8b]: 205e 206 C); IR (KBr) nmax (cm 1): 3383, 3329, 3231 and 3204 (nNH2), 2197 (nCN), 1643, 1566 and 1529 (nC]C); 1H NMR (400 MHz, DMSO-d6): d 8.86 (d, 1H, J ? 2.4 Hz), 8.84 (d, 1H, J ? 2.4 Hz), 7.45 (br s, 2H, NH2); 13C NMR (100 MHz, DMSO-d6):d 154.55 (C), 149.15 (C), 145.26 (CH), 142.36 (CH), 139.76 (C), 115.37 (CN), 74.27 (C); MS (ESI) m/z (%): 177.0 (100) [M th H]th. Anal. Calcd for C7H4N4S: C, 47.72; H, 2.29; N, 31.80; S, 18.20. Found: C, 47.84; H,2.30; N, 31.86.

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:
Article; Loidreau, Yvonnick; Marchand, Pascal; Dubouilh-Benard, Carole; Nourrisson, Marie-Renee; Duflos, Muriel; Lozach, Olivier; Loaec, Nadege; Meijer, Laurent; Besson, Thierry; European Journal of Medicinal Chemistry; vol. 58; (2012); p. 171 – 183;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.

Step A – Preparation of Compound Int- 13cA 5 L- 3 necked round bottomed flask, equipped with a mechanical stirrer, temperature probe, addition funnel and N2 inlet, was charged with the Schollkopf chiral auxiliary-(Int-13a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-13b, 256 g, 1.63 mol, 1.5 eq), and THF (2 L, Aldrich anhydrous). The flask was cooled in a dry ice/ 2- propanol bath until the internal temperature reached -75 ¡ãC. n-Butyllithium (Aldrich 2.5 M in hexanes , 478 mL, 1.19 mol, 1.09 eq) was added via a dropping funnel over 1 hour while maintaining the internal reaction temperature between -67 ¡ãC and -76 ¡ãC. The resulting orange-red solution was allowed to gradually warm to room temperature for about 15 hours. The reaction mixture was then re-cooled to 0 ¡ãC and quenched with 500 mL of water.Diethyl ether (2L) was added and the layers were separated. The aqueous layer was extracted with 1 L of diethyl ether. The combined organic layers was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to dryness, giving 480 g of orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil. The crude product was split into two batches and purified via silica gel chromatography on a 1.6 kg flash column. The column was eluted with gradient of 0-4percent Et20 in hexanes. The product fractions were concentrated in vacuo at a bath temperature at or below 40 ¡ãC giving 190 grams of Int-13c-(60percentyield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DWYER, Michael P; KEERTIKAR, Kartik M; COBURN, Craig A; WU, Hao; HU, Bin; ZHONG, Bin; ZHANG, Chengren; DAN, Zhigang; WO2012/40924; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 762240-92-6,Some common heterocyclic compound, 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, molecular formula is C6H8ClF3N4, 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.

Into a 50 mL round-bottom flask was added 20 mL dichloromethane, followed by the addition of phenyl-butyric acid derivative (3.23 g, 0.01 mol) and triazolopyrazine hydrochloride (228 g, 0.01 mol). The temperature of the reaction mixture was cooled down to 0 C. in an ice-salt bath. 1-Hydroxylbenzotriazole (1.62 g, 0.012 mol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.29 g, 0.012 mol) were further added. 3 g Triethylamine was then added dropwise and the mixture was stirred at room temperature for 24 h. The reaction solution was washed with 3¡Á20 mL distilled water. The obtained organic layers were collected and dried over anhydrous magnesium sulfate for 1 h. Then, the desiccant was filtered off and the resulting reactant was concentrated to 4.67 g. The yield was 94%.

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ZHEJIANG HISOAR PHARMACEUTICAL CO., LTD.; Pan, Xianhua; Li, Weijin; Zhang, Qunhui; Ruan, Libo; Yu, Wansheng; Deng, Fei; Ma, Tianhua; Huang, Mingwang; He, Minhuan; US2013/281695; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 69816-35-9, 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. 69816-35-9 name is 6-(Trifluoromethyl)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) 2-Iodo-6-trifluoromethylpyrazine A three litre flask was charged with a solution of 2-amino-6-trifluoromethylpyrazine (obtained by the method of J.L. Miesel, U.S. Patent 4293552, 95% pure by HPLC analysis, 32.6g, 0.20mol) in chloroform (1000mL). Freshly ground iodine (101g. 0.40mol) was added to give a dark purple solution. After 40 min, a solution of t-butyl nitrite (22.9g, 0.20mol) in chloroform (300mL) was added dropwise over 1h. During the addition, slow gas evolution was observed together with a mild exotherm (< 10C) which was moderated with a cold water bath. After an additional 1h at room temperature the reaction mixture was washed with saturated aqueous sodium sulfite (3 x 500mL) to remove the excess iodine. The chloroform solution was dried over magnesium sulphate, filtered and concentrated on a Buchi to give 23g of an orange oil. The crude product was purified by distillation from copper (40-80 mesh, 200mg) to give 19. 5g of the title compound as a yellow oil; b.p. 50-56C/0.6mmHg; delta (360MHz, CDCl3) 9.06 (1H, s, pyrazine-H), 8.86 (1H, s, pyrazine-H); m/e 274 (M+). At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-(Trifluoromethyl)pyrazin-2-amine, and friends who are interested can also refer to it. Reference:
Patent; MERCK SHARP & DOHME LTD.; EP473442; (1992); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 22047-25-2, A common heterocyclic compound, 22047-25-2, name is Acetylpyrazine, molecular formula is C6H6N2O, 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.

S (346 mg, 10.8mol) and morpholine (2 mL, 20 mmol) were added to a solution of 23 (664 mg, 5.4 mmol) and 24 (1 mL, 6.5 mmol) in t-BuOH (20 mL). The mixture was heated to 60 0C for 18 h. After evaporating t-BuOH, the residue was purified by column chromatography (PE/EtO Ac=I 00: 1) to give 25 (545 mg, 36 % yield).

The synthetic route of 22047-25-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CALCIMEDICA INC.; VELICELEBI, Gonul; STAUDERMAN, Kenneth A.; WHITTEN, Jeffrey P.; PEI, Yazhong; CAO, Jianguo; WANG, Zhijun; ROGERS, Evan; DYCK, Brian; GREY, Jonathan; WO2010/25295; (2010); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 36070-80-1, The chemical industry reduces the impact on the environment during synthesis 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

Using general method 3 (step 1), trans intermediate 19 (150 mg, 0.354 mmol) and 5-chloropyrazine-2-carboxylic acid (67.4 mg, 0.425 mmol) were combined to afford the title compound (140 mg, 0.248 mmol, 70.1%) as a white solid. MS m/z=564.0 (M+H). To the crude tert-butyl ((11bR)-10-amino-3,3,11b-trimethyl-4,4-dioxido-4-a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (190 mg, 0.449 mmol) from Step 4 (-2:1 trans/cis mixture) dissolved in DMF (2 ml), was added 5-chloro-3-methylpyridine-2-carboxylic acid (92 mg, 0.538 mmol), pyridine (0.109 ml, 1.346 mmol) and HATU (256 mg, 0.673 mmol) and resulting solution was stirred for 1 hr at RT. The mixture was diluted with EtOAc (8 ml) and saturated NaHCO3 solution (3 ml). Water was added to dissolve precipitated solids. The organic layer was separated, washed with water, brine and concentrated. The residue was and purified by silica gel chromatography on 12 g RediSep Gold column using 10-70% EtOAc in heptane to afford major less polar trans-isomer tert-butyl ((4aR,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4-a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (110 mg, 0.191 mmol, 42.5% yield and more polar minor cis-isomer tert-butyl ((4aS,11bR)-10-(5-chloro-3-methylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4-a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (70 mg, 0.121 mmol, 27% yield).

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

Reference:
Patent; WHITE, Ryan; ALLEN, Jennifer R.; EPSTEIN, Oleg; HONG, Fang-Tsao; HUA, Zihao; HUMAN, Jason Brooks; LOPEZ, Patricia; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; TAMAYO, Nuria A.; ZHENG, Xiao Mei; US2014/213581; (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. 122-05-4, name is Pyrazine-2,5-dicarboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 122-05-4

5 mmol of (PBTZ)2Ir(Cl)2Ir(PBTZ)2, 25 mmol of pyrazine-2,5-dicarboxylic acid (Py2CA), and 50 mmol of potassium carbonate were mixed in 100 mL of 1,2-dichloroethane, and refluxed for 24 hours under a nitrogen atmosphere. After the reaction was complete, the solution was cooled down to about 50 C. and filtrated. The filtrate solution was purified by using column chromatography to thereby produce (PBTZ)2Ir(Py2CA)Ir(PBTZ)2 at a yield of 82%.

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 122-05-4.

Reference:
Patent; SAMSUNG ELECTRONICS CO., LTD.,; US2008/269484; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem