Month: April 2021

Electric Literature of 22047-25-2, These common heterocyclic compound, 22047-25-2, name is Acetylpyrazine, 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.

General procedure: 1-(Pyrazin-2-yl)ethan-1-one or 1-(5-alkylpyrazin-2-yl)ethan-1-one (0.01 mol) and thecorresponding halogenated benzaldehyde (0.01 mol) were dissolved in pyridine (4.4 mL).Diethylamine (0.01 mol) was added, and the reaction mixture was stirred at 80-120 C for 1 h. Aftercooling, the mixture was poured into ice water (200 mL), acidified to pH 3 with a few drops of aceticacid, and then refrigerated for 24 h. The separation of crude products from water depended on theircharacter. Solids were filtered off and crystallized from anhydrous ethanol, while oily mixtures wereextracted with diethyl ether and subjected to flash chromatography on silica gel. Hexane-ethyl acetatewas used as the eluent in an appropriate ratio (70:30 (v/v), 80:20 (v/v) or 90:10 (v/v)). The fractionscontaining the desired compounds were combined and crystallized from absolute ethanol to obtainanalytically pure crystals.

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

Reference:
Article; Kucerova-Chlupacova, Marta; Vyskovska-Tyllova, Veronika; Richterova-Finkova, Lenka; Kunes, Jiri; Buchta, Vladimir; Vejsova, Marcela; Paterova, Pavla; Semelkova, Lucia; Jandourek, Ondrej; Opletalova, Veronika; Molecules; vol. 21; 11; (2016);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1209646-17-2, A common heterocyclic compound, 1209646-17-2, name is 5-(4-(tert-Butoxycarbonyl)piperazin-1-yl)pyrazine-2-carboxylic acid, molecular formula is C14H20N4O4, 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.

Step 4: synthesis of 5-[5-(l-{5-[5-(piperazin-l-yl)pyrazin-2-yl]-l,2,4-oxadiazol-3- yl}cyclobutyl)pyridin-2-yl]pyrimidin-2-amine (Example 60).Methanol (10.0 mL) is cooled to -5 C and treated with acetyl chloride (1.00 mL). To this mixture is added R51 (0.50 g, 0.90 mmol) and the resulting mixture is stirred for 16 hours. The resulting mixture is treated with 7N ammonia in methanol until basic by pH paper and concentrated in vacuo. The resulting solid is treated with acetonitrile and diluted with water. The mixture is filtered and the filtrate is treated with saturated NaHC03 (3 mL) and the solid is collected by filtration to afford the title compound (90.00 mg). m/z 457.3 [M+H].

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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; BARTOLOZZI, Alessandra; BOSANAC, Todd; CHEN, Zhidong; DE LOMBAERT, Stephane; DINES, Jonathon, Alan; HUBER, John, D.; LIU, Weimin; LOKE, Pui Leng; MORWICK, Tina, Marie; OLAGUE, Alan; RIETHER, Doris; TYE, Heather; WU, Lifen; ZINDELL, Renee, M.; WO2012/40139; (2012); 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 27398-39-6 as follows. Recommanded Product: 3-Chloropyrazine-2-carboxylic acid

Intermediate Y 3-(Pyridin-2-yl)pyrazine-2-carboxylic acid Step 1 : methyl 3-chloropyrazine-2-carboxylate (YD To a solution of 3-chloropyrazine-2-carboxylic acid (100 mg, 0.63 mmol) in DCM/MeOH (2 mL : 0.2 mL) was added TMSCHN2 (0.47 mL, 0.95 mmol) at RT and the resulting mixture was stirred at RT for 2 h. Acetic acid (0.2 mL) was added and the mixture was diluted with water (2 mL) and extracted with DCM (4 mL x 3). The combined organic layers were washed with brine, dried over Na2S04, filtered, and concentrated in vacuo to give the title compound. LRMS m/z (M+H) 173.0 found, 173.0 required.

According to the analysis of related databases, 27398-39-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KIM, Ronald; KUDUK, Scott, D.; LIVERTON, Nigel; ZHUO, Gang; (116 pag.)WO2016/100161; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 32111-21-0, name is 2-Iodopyrazine, 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 32111-21-0, Quality Control of 2-Iodopyrazine

Example 55; N-(3-(5-(4-chlorophenyl’>-4-oxo-6-f4-fpyrazin-2-vDphenyl’)-4.5-dihvdro- 1 H-pyrazolof 3.4- d]p yrirnidin- 1 -yDphenyPmethanesulfonamide; [00189] A solution of N-(3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[ 1 ,3,2]dioxa-borolan-2-yl)phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyriinidin-l -yl} -phenyl)- methane sulfonamide (prepared as described in example 35, 0.50 g, 0.81 mmol) in N,N- dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (0.25 g, 1.21 mmol), cesium carbonate (0.527 g, 1.61 mmol), Pd(dppf)2Cl2 (0.06 g, 0.082 mmol) are added and the resulting solution is degassed with argon for 0.5 h. The reaction mixture is then heated at 100 0C for 3 h. The reaction mixture is cooled to it and diluted with water and extracted with ethyl acetate (3 *). The combined organic layer is washed with brine, dried over Na2SO-I, concentrated, and purified by column chromatography to afford N-{3-[5-(4- chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pytauazolo[3 ,4-d]pyrimidin- 1 -yl]- phenyl} -methane sulfonamide. 1H NMR (DMSO-d6, 400 MHz) delta 10.15 (br, 1 H), 9.26 (d, IH), 8.71 (d, IH), 8.62 (d, IH), 8.52 (s, IH), 8.06 (m, 3H), 7.82 (m, IH), 7.60 (m, 2H), 7.52 (m, IH), 7.40 (m, 4H), 7.18 (m, IH), 3.02 (s, 3H); LC-MS calculated for C28H20ClN7O3S (M+H+) 570.1, found 570.0.

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; IRM LLC; WO2007/120454; (2007); 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. 91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., name: 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine

Step A: To a solution of NaH (60% dispersion in mineral oil, 0.130 g, 3.25 mmol) in THF (10 mL) was added 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.33 g, 2.71 mmol) and the reaction mixture stirred for 10 min. Methyl 2-chlorobenzoxazole-4-carboxylate (478 mg, 2.26 mmol), in THF (10 mL) was added and the reaction mixture was allowed to stir at room temperature 17 h. The reaction mixture was quenched with CH3OH (3 mL), and adsorbed onto silica gel (2 g). The crude product was purified by column chromatography (silica gel, 0.5 to 10% CH3OH in CH2Cl2) to afford methyl 2-(5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)benzoxazole-4-carboxylate (251 mg, 37%) as an orange oil. 1H NMR and MS consistent.

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 91476-80-1.

Reference:
Patent; AMR TECHNOLOGY, INC.; US2008/255114; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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. category: Pyrazines

Select the above embodiment 1The corresponding enamine key intermediate compound of formula II (3.4 mmol)Join the reaction flask, thenAdding the corresponding compound of formula III3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (3.4 mmol)a solution of dichloromethane (50 mL),Control temperature is added at about 0CHOBT (545 mg, 4.2 mmol),Stir for 10 minutes,Then add EDC (1.9g, 10.0mmol),After removing the ice bath,Under stirring, the mixture was slowly heated to room temperature and stirred for 14 hours.After the reaction is over,The reaction solution is concentrated to remove the solvent,Get the corresponding residue,After silica gel column chromatography,The pure fractions are combined and then concentrated to dryness under reduced pressure.This afforded 1.3 g of compound of formula IV-1 as an off-white solid.

The synthetic route of 486460-21-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhejiang Xin Donggang Pharmaceutical Co., Ltd.; Cheng Die; Lin Yi; Yan Jianbo; Hong Huabin; (23 pag.)CN107540677; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 32111-21-0,Some common heterocyclic compound, 32111-21-0, name is 2-Iodopyrazine, molecular formula is C4H3IN2, 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 solution of N- (5-chloro-7-ethynyl-1, 3-benzodioxol-4-yl)-6-methoxy-7- (3- morpholin-4-ylpropoxy) quinazolin-4-amine (0.12g, 0. 24mmol), 3-iodopyrazine (O. lg, 0. 48mmol) and diisopropylamine (0. 066ml, 0. 48mmol) in ethyl acetate (3ml) was cooled to- 20 C under a nitrogen atmosphere. To this was added copper (I) iodide (0.014g, 0.072mmol) and bis (triphenylphospine) palladium (It) chloride (0.034g, 0. 048mmol). The reaction mixture was allowed to warm to ambient temperature and then stirred overnight. The mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 0-10% methanol in dichloromethane to give the product as a light yellow solid (0.052g, 38%). NMR Spectrum: (DMSOd6) 1.99 (t, 2H), 2.40 (brs, 4H), 2.50 (t, 2H) partially obscured by DMSO peak, 3.59 (s, 4H), 3.97 (s, 3H), 4.23 (t, 2H), 6.27 (s, 2H), 7.19 (s, 1H), 7.35 (s, 1H), 7.89 (s, 1H), 8.42 (s, 1H), 8.74 (s, 1H), 8.78 (s, 1H), 8.96 (s, 1H), 9.66 (s, 1H). Mass Spectrum: M+H+ 575 and M+H-573.

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

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/4732; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 17890-77-6, 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 17890-77-6 as follows.

To a solution of 3-amino-6-bromopyrazine-2-carboxamide (200 mg, 0.92 mmol) in triethoxymethane (10 mL) was added Ac20 (2 mL). The mixture was stirred at 130C for 1 h and 90C for 3 h. After being cooled to RT and extracted with EtOAc, the combined organic phaseswere basified to pH = 8 with a.q. NaHCO3, washed with brine, dried over Na2504, filtered andevaporated. The crude product was purified by prep-TLC (DCM : MeOH = 50: 1) to give theproduct of 6-bromopteridin-4(3H)-one (100 mg, yield: 48%). ?H-NMR (DMSO-d6, 400 MHz)8.59 (s, 1H), 7.89 (s, 1H). MS (M+H): 227 / 229.

According to the analysis of related databases, 17890-77-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DAI, Xing; LIU, Hong; PALANI, Anandan; HE, Shuwen; NARGUND, Ravi; XIAO, Dong; ZORN, Nicolas; DANG, Qun; MCCOMAS, Casey C.; PENG, Xuanjia; LI, Peng; SOLL, Richard; WO2014/205593; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 54608-52-5, These common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, 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 mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), prepared from 2-chloropyrazine and hydrazine using a procedure analogous to that described in the literature (P. J. Nelson and K. T. Potts, J. Org. Chem. 1962, 27, 3243, except that the crude product was extracted into 10% methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate followed by 10% methanol in dichloromethane), TFA (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140 C. with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted with ethyl acetate (3¡Á), washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexane:ethyl acetate, then 100% ethyl acetate) afforded the title compound as a solid (861 mg). 1H NMR (500 MHz, CDCl3) delta 8.17-8.20 (m, 2H), 9.54 (s, 1H). LC/MS (M+1) 189

Statistics shows that 2-Hydrazinopyrazine is playing an increasingly important role. we look forward to future research findings about 54608-52-5.

Reference:
Patent; Merck Sharp & Dohme Corp.; Edmondson, Scott D.; Fisher, Michael H.; Kim, Dooseop; Maccoss, Malcolm; Parmee, Emma R.; Weber, Ann E.; Xu, Jinyou; US2015/359793; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 41270-66-0, 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. 41270-66-0 name is 5-Chloro-2,3-diphenylpyrazine, 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.

Step 3: 2-Azido-5,6-diphenylpyrazine. To a stirred solution of 2-Chloro-5,6-diphenylpyrazine (45 mg, 0.17 mmol) in 500 muL DMF at room temperature under nitrogen was added sodium azide (11 mg, 0.17 mmol) and the reaction was warmed to 100 C. After stirring overnight, the reaction was cooled to room temperature, diluted with EtOAc (30 mL) and washed 4*30 mL with H2O and 1*30 mL with saturated NaCl. The organics were islolated, dried (MgSO4), filtered and concentrated to the 2-azidopyrazine, which exists as a yellow solid (45 mg, quantitative). 1H-NMR (400 MHz, CDCl3) delta9.73 (s, 1H), 7.58-7.42 (m, 6H), 7.36-7.23 (m, 4H).

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

Reference:
Patent; Keegan, Kathleen S.; Kesicki, Edward A.; Gaudino, John Joseph; Cook, Adam Wade; Cowen, Scott Douglas; Burgess, Laurence Edward; US2003/69284; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem