Tag: M.W=200-300

Reference of 1379338-74-5, A common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, molecular formula is C7H3Cl2N3, 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.

Intermediate 20: 1,1-Dimethylethyl (2S)-2-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)oxy]methyl}-4-morpholinecarboxylate 1,1-Dimethylethyl (2S)-2-(hydroxymethyl)-4-morpholinecarboxylate (Preparation reference: WO 2009/071658) (586 mg, 2.70 mmol) was dissolved in N,N-Dimethylformamide (7 mL) and cooled in an ice bath to 5 C. under a nitrogen atmosphere. Sodium hydride 60% in mineral oil (162 mg, 4.05 mmol) was added portionwise over 15 min. 5,7-dichloropyrido[3,4-b]pyrazine (647 mg, 3.24 mmol) was then added portionwise and the mixture stirred at 5 C. for 35 min and quenched by addition of saturated aqueous ammonium chloride solution (20 mL). The solution was partitioned between ethyl acetate and water. The aqueous was re-extracted with ethyl acetate and the combined organic layers were washed with water, separated using a phase separation cartridge and the solvent removed to give a brown solid. The crude residue was dissolved in DCM and purified by silica chromatography eluting with a 12-62% ethyl acetate in petroleum ether gradient. The appropriate fractions were combined and the solvent was evaporated to give the title compound as a brown solid (917 mg). LCMS (Method B): Rt=1.12 min, MH+=380.9

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; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Atkinson, Stephen John; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander G.; Shipley, Tracy Jane; Wilson, David Matthew; Watson, Robert J.; US2014/5188; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1458-01-1, The chemical industry reduces the impact on the environment during synthesis 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

Preparation 1 3-Chloro-pyrazine-2,6-diamine Lithium hydroxide (12.4 g, 0.30 mol) was added to a stirred suspension of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester (20 g, 99 mmol) in methanol (300 ml) and water (120 ml) and the reaction heated at 90¡ã C. for 1.5 hours before allowing to cool to room temperature. The reaction was concentrated in vacuo to afford a yellow slurry and this was suspended in 1,4-dioxane (350 ml) and 2M aqueous HCl solution (200 ml,) was added. The mixture was heated at 100¡ã C. for 2 hours and then allowed to cool before removing the 1,4-dioxane in vacuo. The resulting aqueous solution was taken to pH 8 using sodium carbonate (saturated aqueous) and extracted into ethyl acetate (3*300 ml). The combined organic layers were washed with brine (300 ml), dried (Na2SO4) and concentrated in vacuo to afford a yellow solid (11.7 g, 82percent). 1H-NMR (d6-DMSO): 5.95 (br s, 2H), 6.02 (br s, 2H), 6.82 (s, 1H). MS m/z 147 [MH]+

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, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Pfizer Limited; US2007/105872; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1458-18-0, 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. 1458-18-0 name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 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 1: Methyl 3-amino-6-chloro-5-(2-fluorophenyl)pyrazine-2-carboxylate A mixture of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate (10.0 g, 45 mmol, Ark Pharm, Inc., Arlington Heights, Ill.), (2-fluorophenyl)boronic acid (6.93 g, 49.5 mmol, Combi-Blocks, San Diego, Calif., USA) and potassium carbonate (13.1 g, 95 mmol) in a 10:1 mixture of DME/water (220 mL) was degassed with nitrogen for 5 min and then tetrakis(triphenylphosphine)palladium(0) (1.04 g, 0.90 mmol) was added. The reaction mixture was stirred at 90 C. for 16 h, then was allowed to cool to room temperature and partitioned between EtOAc (200 mL) and 1 N HCl (200 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to provide methyl 3-amino-6-chloro-5-(2-fluorophenyl)pyrazine-2-carboxylate. m/z (ESI, +ve): 282.1 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; Amgen Inc.; LANMAN, Brian Alan; CHEN, Jian; REED, Anthony B.; CEE, Victor J.; LIU, Longbin; KOPECKY, David John; LOPEZ, Patricia; WURZ, Ryan Paul; NGUYEN, Thomas T.; BOOKER, Shon; NISHIMURA, Nobuko; SHIN, Youngsook; TAMAYO, Nuria A.; ALLEN, John Gordon; ALLEN, Jennifer Rebecca; (266 pag.)US2018/334454; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 63744-22-9,Some common heterocyclic compound, 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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 250-mL 3 -necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, were placed 6,8-dibromoimidazo[l,2-a]pyrazine (5 g, 18.06 mmol, 1.00 equiv) and /V, /V-di methyl formam i dc (125 mL). This was followed by the addition of (0249) NIS (4.3 g, 19.11 mmol, 1.05 equiv), in portions at room temperature. The resulting solution was stirred overnight at 60 C in an oil bath. The reaction mixture was cooled to room temperature with a water/ice bath and then quenched with water. The resulting solution was extracted with ethyl acetate and the organic layers combined and concentrated under vacuum. Purification by flash chromatography (silica gel column with ethyl (0250) acetate/petroleum ether (1/2)) provided 2.8 g (38%) of 5-1 as a white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6,8-Dibromoimidazo[1,2-a]pyrazine, its application will become more common.

Reference:
Patent; IDEAYA BIOSCIENCES, INC.; BECK, Hilary, Plake; GONZALEZ-LOPEZ, Marcos; SUTTON, James, Clifford, Jr.; (86 pag.)WO2019/156989; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 144692-85-3, name is 2,3-Dichlorofuro[3,4-b]pyrazine-5,7-dione belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Formula: C6Cl2N2O3

To a solution of 5b (100mg, ca. 31mumol) and 4 (111mg, 10.2mumol) in dry DMF (5mL) was added DiPEA (91muL, 51.2mumol). The reaction was then stirred at 40C for 36h. The solvent was removed in vacuo and subsequently co-evaporated with toluene (3¡Á2mL). The crude material was purified by gradient column chromatography (SiO2; CH2Cl2/EtOAc 100:0?95:5) to afford analytically pure 1b as a white solid. Yield=95mg (59%). (0016) 1H NMR (500MHz, CDCl3): delta 8.17 (s, 4H, ArH), 7.92-7.94 (m, 4H, ArH), 7.45-7.49 (m, 4H, ArH), 7.23 (s, 4H, ArH), 5.65 (t, 3JHH=8.0, 2H, ArCH), 5.53 (t, 3JHH=8.4, 2H, ArCH), 4.12 (t, 3JHH=6.3, 4H, CH2), 3.46 (t, 3JHH=6.3, 4H, CH2), 2.21-2.31 (m, 8H, CHCH2), 1.25-1.50 (m, 32H, CH2), 0.90-0.95 (m, 12H, CH3). 13C{1H} NMR (126MHz, CDCl3): delta 162.2, 158.5, 153.1, 152.2, 141.5, 139.8, 136.8, 135.6, 129.7, 128.4, 123.8, 118.8, 39.8, 34.4, 32.7, 32.4, 32.0, 29.5, 29.5, 28.1, 27.8, 22.8, 14.2. HR ESI-MS positive ion: 1603.4086m/z [M+Na]+ (calc. 1603.4212). Anal. Calcd for C84H80Br2N10O12 (1581.43gmol-1): C, 63.80; H, 5.10; N, 8.86. Found: C, 63.83; H, 5.01; N, 8.80.

The synthetic route of 144692-85-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Knighton, Richard C.; Chaplin, Adrian B.; Tetrahedron; vol. 73; 31; (2017); p. 4591 – 4596;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 51171-02-9, A common heterocyclic compound, 51171-02-9, name is Methyl 3-Bromo-2-pyrazinecarboxylate, molecular formula is C6H5BrN2O2, 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.

(B) Methyl 2-phenylamino-3-pyrazine carboxylate: A mixture of 9.5 g. of methyl 2-bromo-3-pyrazine carboxylate, 8.2 g. of aniline, 0.5 g. of p-toluene sulfonic acid and 100 ml. of water is stirred and refluxed for two hours. The reaction mixture is poured on ice, extracted with ethyl acetate, the organic extracts are dried and concentrated to yield an oil. The crude residue is eluted on a silica gel column with ethylacetate-hexane (1:2) yielding the product of this example as a yellow solid, m.p. 72-75 C.

The synthetic route of 51171-02-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Schering Corporation; US4551463; (1985); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-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. HPLC of Formula: C7H3Cl2N3

Intermediate 18: 1,1-Dimethylethyl (3S)-3-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)oxy]methyl}-1-piperidinecarboxylate 1,1-Dimethylethyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate (129 mg, 0.600 mmol) (Apollo Scientific Limited) was taken up in N,N-dimethylformamide (DMF) (3 ml), treated with sodium hydride (23.99 mg, 0.600 mmol) and allowed to stir at room temperature for 20 min, a yellow solution resulted. 5,7-dichloropyrido[3,4-b]pyrazine (100 mg, 0.500 mmol) was added and the reaction was allowed to stir at room temperature for a further 1 h. The reaction was partitioned between EtOAc (50 ml) and NH4Cl (50 ml). The organic layer was dried using a hydrophobic frit and concentrated to give a brown oil. This oil was purified on silica (25 g) using a 0-40% EtOAc/cyclohexane gradient. The appropriate fractions were summed and concentrated to give the title compound as a yellow gum (91 mg). LCMS (Method B): Rt=1.26 min, MH+=378.88

The synthetic route of 5,7-Dichloropyrido[3,4-b]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Atkinson, Stephen John; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander G.; Shipley, Tracy Jane; Wilson, David Matthew; Watson, Robert J.; US2014/5188; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 41270-66-0, 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. 41270-66-0, name is 5-Chloro-2,3-diphenylpyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To the stirred mixture of 5-chloro 2-3 diphenyl pyrazine (100 g, 0.375 mol) & 4-lsopropylamino-butyric acid ethyl ester (257.97 g, 1.49 mol) was added at room temperature. Reaction mixture was stirred at 185-190C temperature for 24 hr. Reaction was monitored by HPLC analysis. After completion of reaction, charged purified Water and product extracted in Ethyl acetate, which was washed using 5% sodium bicarbonate to remove the hydroxyl impuritiy produced during the reaction. Then the ethyl acetate layer was concentrated to obtain the 4-[(5,6-diphenyl-pyrazin-2-yl)-isopropyl-amino]- butyric acid ethyl ester. [Yield = 90 g; Purity (HPLC) = 88.71 %]

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

Reference:
Patent; MEGAFINE PHARMA (P) LTD.; MATHAD VIJAYAVITTHAL THIPPANNACHAR; DODDAPPA PRALHAD ANEKAL; KARDILE PRITESH BHIMRAJ; PADAKI SANTHOSH AMBADAS; GAIKWAD BAPUSAHEB SHRIHARI; SHINDE GORAKSHANATH BALASAHEB; (63 pag.)WO2017/42828; (2017); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 622392-04-5, name is 2-Bromo-5-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 622392-04-5, category: Pyrazines

Add 30 g of 2-bromo-5-iodopyrazine, 300 ml of toluene to a 500 ml three-necked flask.Displace nitrogen protection and then add 26.7 ml of hexa-butyltin di-tin.After the reaction solution was stirred at room temperature for 3 hours,0.61 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 120 C and stirred for 8 hours.The TLC monitors the complete reaction of the starting material to stop the reaction.After the reaction solution is cooled to room temperature, the column removes insoluble impurities.The crude product obtained after concentration of the eluent was recrystallized from toluene to yield 12.6 g of white solid.The yield was 76.2%.

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

Reference:
Patent; Xi’an Ruilian New Materials Co., Ltd.; Zhang Hongke; Sun Jun; Liu Kaipeng; Wang Xiaowei; Liu Qianfeng; Gao Renxiao; Cai Liang; Yang Yan; (34 pag.)CN109053696; (2018); A;,
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 117719-17-2 as follows. SDS of cas: 117719-17-2

A mixture of 5-bromo-3-morpholin-4-yl-pyrazin-2-ylamine (1.4 g, 4.1 mmol) and 2- bromo-5,5-dimethylcyclohexane-1 ,3-dione (0.9 g, 6.1 mmol; intermediate I-09) in DME (4 mL) was heated at 120 C for 16 h. The reaction mixture was cooled to rt, diluted with DCM (20 mL), washed with aqueous saturated NaHC03 (2 x 30 mL), brine (20 mL), dried over Na2S04 and concentrated in vauco. The dark crude was purified by Biotage flash column chromatography, eluting with a solvent system of EtOAc/cyclohexane (from 20% to 75% on EtOAc), yielding the required product, intermediate I-08, as a pale yellow solid (430 mg, 22%).

According to the analysis of related databases, 117719-17-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONC&Oacgr;LOGICAS (CNIO); PASTOR FERNANDEZ, Joaquin; MARTINEZ GONZALEZ, Sonia; ALVAREZ ESCOBAR, Rosa Maria; RODRIGUEZ ARISTEGUI, Sonsoles; GONZALES CANTALAPIEDRA, Esther; HERNANDEZ HIGUERAS, Ana Isabel; VARELA BUSTO, Carmen; WO2011/36461; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem