Month: April 2021

These common heterocyclic compound, 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, 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 2-Bromo-5H-pyrrolo[2,3-b]pyrazine

To a solution of 2-bromo-5H-pyrrolo[3,2-Z?]pyrazine (0.68 g, 3.4 mmol) in acetone (17 mL) was added N-iodosuccinimide (0.82 g, 3.6 mmol) and the resulting mixture was stirred for 4 h at rt. The mixture was evaporated in vacuo to yield a residue that was purified via silica gel chromatography eluting with 40% THF in hexanes to give the title compound as a yellow solid (0.99 g, 89%). NMR (DMSO-i , 300 MHz): delta 12.82 (s, 1H), 8.42 (s, 1 H), 8.20 (s, 1 H). HPLC retention time: 2.23 minutes. MS ESI (m/z): 324.0, 326.0 (M+H)+, calc. 323.

The synthetic route of 2-Bromo-5H-pyrrolo[2,3-b]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNIVERSITY OF ROCHESTER; BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA; GELBARD, Harris A.; DEWHURST, Stephen; GENDELMAN, Howard E.; WO2014/85795; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 63744-22-9, name is 6,8-Dibromoimidazo[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 63744-22-9, Product Details of 63744-22-9

To a solution of 4-(4- (oxetan-3-yl)piperazin- l-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)aniline XXIV (619 mg, 2.17 mmol) and 6,8-dibromoimidazo[l,2-a]pyrazine (601 mg, 2.2 mmol) in IPA (15 mL) was added N,N-Diisopropylethylamine (0.95 ml, 5.43 mmol). The mixture was stirred at 110 C for 16 h. After this time, DCM (10 mL) and sat aqueous NaHC03 (15 mL) were added. The aqueous layer was separated and extracted with DCM (2 x 10 mL). The combined organic extracts were washed with brine (10 mL) and dried over sodium sulfate. The resulting residue was purified by column chromatography ISCO Rf (24 g column) eluting with a gradient of 100% DCM – 60:35:5 DCM : Et20 : MeOH to provide 6-bromo-N- (4-(4-(oxetan-3-yl)piperazin-l-yl)-3-(2-((tetrahydro-2H-pyran-2- yl) oxy)ethoxy)phenyl)imidazo [ 1 ,2- a] pyrazin- 8 -amine XXV .

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, 6,8-Dibromoimidazo[1,2-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GILEAD SCIENCES, INC.; BLOMGREN, Peter, A.; CURRIE, Kevin, S.; KROPF, Jeffrey E.; LEE, Seung H.; LO, Jennifer R.; MITCHELL, Scott A.; SCHMITT, Aaron C.; XIONG, Jin-Ming; XU, Jiangjun; ZHAO, Zhongdong; WO2015/100217; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

54608-52-5, name is 2-Hydrazinopyrazine, 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. HPLC of Formula: C4H6N4

In a 8 mL vial with magnetic stirrer and screw cap, ethyl 4-chloro-7- methoxyquinoline-3-carboxylate (70 mg, 0.26 mmol, 1 equiv.) and 2-hydrazinopyrazine (32 mg, 0.29 mmol, 1.1 equiv.) were dispersed in 1.5 mL ethanol, triethylamine (40 muL, 0.29 mmol, 1.1 eq.) was added and the reaction mixture was heated to reflux under argon atmosphere. After 20 h the reaction mixture was rinsed with 4 mL water, filtered and the precipitate was washed with 15 mL EtOAc/PE (1/1). The yellow solid was dried under reduced pressure to give the desired product. Yield: 58% (0.15 mmol, 45 mg), Appearance: yellow solid, TLC: 0.38 (10% MeOH in CH2Cl2), M.p.: >300 C, 1H NMR (400 MHz, DMSO- d6) delta 3.88 (s, 3H), 7.16- 7.23 (m, 2H), 8.13 (dd, J = 8.5, 0.8 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 2.5, 1.5 Hz, 1H), 8.75 (s, 1H), 9.51 (d, J = 1.4 Hz, 1H), 12.74 (br s, 1H).13C NMR (101 MHz, DMSO-d6) delta 55.6 (q), 102.1 (d), 105.0 (s), 112.2 (s), 115.5 (d), 123.9 (d), 136.6 (d), 137.3 (s), 140.0 (d), 140.1 (d), 142.8 (d), 144.9 (s), 148.0 (s), 160.8 (s), 162.4 (s). HR-MS: Calc.[M+H]+ m/z (predicted) = 294.0992, m/z (measured) = 294.0992, difference = 0.00 ppm.

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UWM RESEARCH FOUNDATION, INC.; MEDICAL UNIVERSITY OF VIENNA; NATIONAL TAIWAN UNIVERSITY; UNIVERSITY OF BELGRADE-FACULTY OF PHARMACY; CHIOU, Lih-Chu; COOK, James; ERNST, Margot; FAN, Pi-Chuan; KNUTSON, Daniel; MEIRELLES, Matheus; MIHOVILOVIC, Marko; SIEGHART, Werner; VARAGIC, Zdravko; VERMA, Ranjit; WIMMER, Laurin; WITZIGMANN, Christopher; SIEBERT, David, Chan Bodin; SAVIC, Miroslav, M.; (170 pag.)WO2016/196961; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 113305-94-5,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.

2-Amino 5-cyano pyrazine (0.25 g, 2.08 mmol) was dissolved in THF and DCM (3:1 , 40 ml_) and pyridine (0.49 g, 6.2 mmol) was added. The mixture was stirred for 15 minutes. Phenylchloroformate (0.97 g, 6.2 mmol) was added and the reaction mixture was heated at 50C for 2 hours. The reaction mixture was cooled to RT and DCM (40 mL) and water (25 mL) were added. The separated organic layer was washed with water (2 x 25 mL), brine (25 mL), dried (Na2S04) and the solvents evaporated under reduced pressure. The product was purified by column chromatography on neutral silica gel using 15-20% EtOAc in hexane to give the title compound (0.29g, 54%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Aminopyrazine-2-carbonitrile, its application will become more common.

Reference:
Patent; SENTINEL ONCOLOGY LIMITED; BOYLE, Robert George; WALKER, David Winter; BOYCE, Richard Justin; WO2011/141716; (2011); A2;,
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.

This compound was prepared by following Suzuki coupling mechanism where methyl 5-(chloropyrazine)-2-carboxylate, a commercially available starting material 36 7 (2g, 0.0115mmol) was reacted with 44 phenyl boronic acid (1.4g, 0.0115mmol) using 45 bis(triphenylphosphine) palladium(II)dichloride (0.163g, 0.0002mmol) as catalyst, 146 potassium carbonate (2.4g, 0.01737mmol) as base and 1,4-dioxane as solvent for 12h at 100C. After completion of the reaction, the solvent was evaporated and crude was extracted in 106 ethyl acetate and washed with water. The organic layer was dried over sodium sulfate and crude was purified by column chromatography (hexane: EtOAc; 9:1) to get 1g of pure white crystalline solid intermediate 47 19 (yield 40.16%). 1H NMR (400MHz, DMSO-d6) delta 9.42 (d, J=1.4Hz, 1H), 9.25 (d, J=1.4Hz, 1H), 8.27-8.23 (m, 2H), 7.62-7.57 (m, 3H), 3.95 (s, 3H). C12H12N2O2 [M]: 214.22; MS (ESI) m/z: [M+H]+: 215.10.

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

Reference:
Article; Trivedi, Prakruti; Adhikari, Nilanjan; Amin, Sk. Abdul; Jha, Tarun; Ghosh, Balaram; European Journal of Pharmaceutical Sciences; vol. 124; (2018); p. 165 – 181;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 36070-80-1, 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of lenalidomide (0.2g, 0.77 mmol) in DMF (4 mL) was added 5-chloropyrazine-2-carboxylic acid (0.15g, 0.95 mmol), HATU, (0.29g, 0.77 mmol), and DIPEA (0.27mL, 1.54 mmol). The reaction was stirred at room temperature for 1 hr before it was quenched with saturated NH4C1 (5 mL). The mixture was extracted with EtOAc (10 mLx3), and the combined organic phase was dried over Na2S04 and concentrated. Column chromatography gave 5-chloro-N- (2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl)pyrazine-2-carboxamide (0.1 g, 33%).

The chemical industry reduces the impact on the environment during synthesis 5-Chloropyrazine-2-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SYNTA PHARMACEUTICALS CORP.; CHIMMANAMADA, Dinesh, U.; YING, Weiwen; ZHANG, Junyi; KOWALCZYK-PRZEWLOKA, Teresa; JIANG, Jun; OSMAN, Sami; LU, Genliang; VUTUKURI, Dharma; LOCH, James; CHEN, Shoujun; WO2015/38649; (2015); 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 33332-28-4 as follows. category: Pyrazines

p. N-(6-Chloro-2-pyrazinyl)-4-hydroxy-2-methyl-2H-naphtho[2, 1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide, m.p. 209¡ã-210¡ã C (from ethanol), from 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1 -e]-1,2-thiazine-3-carboxylic acid chloride-1,1-dioxide and 2-amino-6-chloro-pyrazine.

According to the analysis of related databases, 33332-28-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Boehringer Ingelheim GmbH; US3992535; (1976); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, 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 33332-25-1, Product Details of 33332-25-1

Example 2[6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin- 1-yl)-pyrazin-2-yl] -((R)-2-methyl- pyrrolidin- 1-yl)-methanonea) 5- (3 ,3-Difluoro-azetidin- 1 -yl)-pyrazine-2-carboxylic acid methyl ester 5-Chloro-pyrazine-2-carboxylic acid methyl ester (CAN 33332-25-1; 15 g, 86.92 mmol) was dissolved in dioxane (100 mL). To this solution was added 3,3-difluoroazetidine hydrochloride (CAN 288315-03-7; 13.51 g, 104.31 mmol), and triethyl amine (31.3 mL,226 mmol). The mixture was stirred 22 hours at 45C and afterwards cooled to room temperature. Brine (100 mL) was added and the mixture was extracted with ethyl acetate. The organic phases were washed successively with sodium bicarbonate solution (10%, 300 mL) and brine (200 mL); dried with Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 200g, 30% to 50% ethyl acetatein hexane) to give the desired product (15 g, 75.3%) as white solid; LC-MS (UV peak area, ESI) 98.6%, 230.4 [MH?i.

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DHURWASULU, Baledi; GRETHER, Uwe; NETTEKOVEN, Matthias; ROEVER, Stephan; ROGERS-EVANS, Mark; SCHULZ-GASCH, Tanja; WO2014/86807; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 41110-28-5, name is 3-Methylpyrazine-2-carboxylic acid, 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 41110-28-5, Product Details of 41110-28-5

In a 2-L flask, 3-methylpyrazine-2-carboxylic acid (Matrix, 19.95 g, 144 mmol) was suspended in MeOH (500 mL). The suspension was cooled in an ice-water bath, and concentrated sulfuric acid (Fluka, 27.3 mL, 506 mmol) was added over a time period of 5 min. The reaction mixture was heated to 80 C for 5 h. The reaction mixture was concentrated under reduced pressure and the residue was taken up in DCM (750 mL). The excess acid was neutralized carefully with of aqueous NaOH (5 M, 200 mL). The aqueous layer was separated and extracted with DCM (250 mL). The combined organic layers were combined, dried over MgSO4 and concentrated to afford 16.15 g of methyl 3-methylpyrazine-2-carboxylate (265A, 106 mmol, 73%). MS m/z=153 [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; AMGEN INC.; ALLEN, Jennifer R.; AMEGADZIE, Albert; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Jian J.; CHENG, Yuan; FROHN, Michael J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul E.; LIU, Longbin; LIU, Qingyian; LOW, Jonathan D.; MA, Vu Van; MANNING, James; MINATTI, Ana Elena; NGUYEN, Thomas T.; NISHMURA, Nobuko; NORMAN, Mark H.; PETTUS, Liping H.; PICKRELL, Alexander J.; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; SIEGMUND, Aaron C.; STEC, Markian M.; WHITE, Ryan; XUE, Qiufen; (759 pag.)WO2016/22724; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 6863-74-7, These common heterocyclic compound, 6863-74-7, name is 6-Chloropyrazine-2-carbonitrile, 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.

Reference Example 109 2-Cyano-6-[2-(dimethylamino)ethylthio]pyrazine 2-Dimethylaminoethanethiol hydrochloride salt (1.46 g, 10.0 mmol) and sodium hydride (60 % in oil, 0.88 g, 22.0 mmol) were added to THF (50 ml), and 2-chloro-6-cyanopyrazine (1.40 g, 10.0 mmol) was added thereto.. The mixture was stirred at room temperature for 18 hrs.. The reaction mixture was combined with ethyl acetate and water.. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate.. The solvent was evaporated, and the residue was recrystallized from n-hexane-ethyl acetate to give the titled compound (1.00 g, 48 %) as pale yellow crystals.1H-NMR (CDCl3) delta: 2.32 (6H, s), 2.62-2.67 (2H, m), 3.31-3.38 (2H, m), 8.48 (1H, s), 8.58 (1H, s). IR(KBr): 2233, 1576, 1549, 1456, 1143, 794 cm-1.

The synthetic route of 6863-74-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Chemical Industries, Ltd.; EP1424336; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem