Month: April 2021

Reference of 14508-49-7, These common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, 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.

The starting compound 3-chloropyrazine-2-carboxamide was synthesized using two published procedures. The first method was classified as less effective and was based on the homolytic amidation of 2-chloropyrazine. Thus, 2-chloropyrazine (0.17 mol) was dissolved in formamide (3.7 mol), heated to 90 C and ammonium peroxodisulphate (0.18 mol) was added portionwise over one hour period. This mixture reacted for another one hour at 90 C and then it was left to stand for 24 h at laboratory temperature. Dilution with 100 mL of water was followed by filtration and this filtrate was extracted continuously with chloroform for 16 h [34,42]. The mixture of three positional isomers was separated by flash chromatography using silica gel as stationary phase. The second process used 3-chloropyrazine-2-carbonitrile, which was submitted to partial hydrolysis of the nitrile group. The powdered carbonitrile (0.104 mol) was added little by little into the reaction mixture of concentrated hydrogen peroxide (0.95 mol) and water (195 mL) heated to 50 C. The pH was adjusted and regulated around a value of 9 using an 8% solution of sodium hydroxide and the temperature of the reaction was regulated between 55 and 60 C. The reaction was stopped after 2.5 h and was cooled to 5 C. Newly-emerged crystals were removed by suction and recrystallized from ethanol [42].

Statistics shows that 2-Chloropyrazine is playing an increasingly important role. we look forward to future research findings about 14508-49-7.

Reference:
Article; Jandourek, Ondrej; Dolezal, Martin; Kunes, Jiri; Kubicek, Vladimir; Paterova, Pavla; Pesko, Matus; Buchta, Vladimir; Kralova, Katarina; Zitko, Jan; Molecules; vol. 19; 7; (2014); p. 9318 – 9338;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 19847-12-2, 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 19847-12-2 as follows.

General procedure: Sodium metal (23 mg) was dissolved in absolute methanol (20 ml) and was labeled as sodium methoxide solution in methanol. 2-Cyanopyridine (0.210 ml, 2 mmol) was dissolved in absolute methanol (10 ml) and to it was added sodium methoxide solution (0.5 ml) prepared above, the reaction contents were stirred at room temperature for 2 h. 4-(2-Aminoethyl) morpholine (0.26 ml, 2 mmol) was added to the reaction mixture. The reaction contents were heated under reflux for 8 h. Solvent was removed under reduced pressure and to the residue left behind was added diethyl ether, solid so obtained was filtered and washed with diethyl ether to give crude product. This crude product was purified by crystallization from ethyl acetate/methanol to give pure N-(2-morpholin-4-yl-ethyl)-pyridine-2-carboxamidine (3a).

According to the analysis of related databases, 19847-12-2, the application of this compound in the production field has become more and more popular.

Reference:
Article; Arya, Surbhi; Kumar, Nikhil; Roy, Partha; Sondhi; European Journal of Medicinal Chemistry; vol. 59; (2013); p. 7 – 14;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5049-61-6, These common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, 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.

Stage preparation of imidazo[1,2-a]pyrazine A mixture of 34 g (0.2 mol) of bromoacetaldehyde dimethyl acetal, 6,6 ml of concentrated aqueous HBr solution and 28 ml of distilled water is brought to reflux for one hour. After reaction, the mixture is alkalinized and extracted with ether. This organic phase is added to a solution of 19 g (0.2 mol) of aminopyrazine in 50 ml of dimethylformamide (DMF). The ether is removed by distillation and the mixture is maintained with stirring and under a stream of nitrogen for 12 hours. After reaction, the DMF is distilled off; the reaction medium is dissolved in 150 ml of anhydrous ethanol, and then brought to reflux for one hour. The alcohol is then removed by distillation; the residue is dissolved in water, alkalinized with Na2 CO3 and extracted using dichloromethane. After chromatography on a neutral alumina column (eluant =anhydrous ether), 10.7 g (Yld=45%) of imidazo[1,2-a]pyrazine (m.p. 84 C.). are obtained.

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; l’Universite de Montpellier I; US5028605; (1991); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 723286-80-4, 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 723286-80-4 as follows.

A mixture of tert-butyl 3-bromo-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carboxylate (1.65 mmol, 500 mg), 1-chloro-3-ethynyl-benzene ( 3.3 mmol, 450.5 mg, 0.406 mL), Pd tetrakis (0.083 mmol, 95.3 mg) and sodium acetate (3.3 mmol, 448.9 mg) in DMF anhydrous (10 mL) was stirred at 120C in a MW Biotage Robot 8 oven for 10 minutes, cooled to r.t., poured into water and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed in vacuo and the crude residue was purified via automated flash chromatography (Biotage Isolera, SNAP25 cartridge) eluted with Petroleum ether/EtOAc gradient from 30% to 100% of EtOAc. (0197) The title product (280 mg, 47 % yield) was isolated as a pale yellow solid.

According to the analysis of related databases, 723286-80-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.P.A; GRAZIANI, Davide; RIVA, Carlo; MENEGON, Sergio; TAZZARI, Valerio; (98 pag.)WO2019/145214; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 221136-66-9, 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. 221136-66-9, name is Ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Example 8 r3-(2,2-Difluoro-2-phenyl-ethylamino)-6-methyl-2-oxo-2H-pyrazin-1-vn- acetic acid ethyl ester(3-Bromo-6-methyl-2-oxo-2H-pyrazin-1 -yl)-acetic acid ethyl ester was reacted with 2,2-difluoro-2-phenyl-ethylamine in the presence of a base, at elevated temperature, to yield the title compound as shown in the Scheme above. Table 5 below lists the reagent amounts, base and temperature combinations applied to this reaction, as well as 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, Ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JANSSEN PHARMACEUTICA, N.V.; WO2007/146553; (2007); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 193966-70-0, name is Methyl 5-(bromomethyl)pyrazine-2-carboxylate, 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. Computed Properties of C7H7BrN2O2

[0116j To a solution of methyl 5-(bromomethyl)pyrazine-2-carboxylate (0.15 g, 0.65 mmol) in chloroform (10 mL) was added hexamethylene tetramine (0.093 g, 0.66 mmol) and the reaction mixture was stirred at room temperature for 18 h. The solid formed was filtered and dried. The solid was suspended in methanol (10 mL), concentrated hydrochloric acid (0.3 ml) was added and the reaction mixture was heated at 75 C for 3 h. The reaction mixture was concentrated, the residue was triturated with diethyl ether and dried to afford the title compound methyl 5-(aminomethyl)pyrazine-2-carboxylate hydrochloride (0.15 g, crude) as a brownish solid. Calculated M+H: 168.07; Found M+H: 168.1.

The synthetic route of Methyl 5-(bromomethyl)pyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MNEMOSYNE PHARMACEUTICALS, INC.; ANDERSON, David R.; VOLKMANN, Robert A.; WO2015/48503; (2015); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 5049-61-6, 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 5049-61-6 as follows.

A mixture of 2-aminopyrazin (25 g, 262.9 mmole), chloroacetaldehyde (50% in water, 50 ml, 394 mmole) and NaHCO3 (33.1 g, 394 mmole) was heated for 2 days at 100 C. The reaction mixture was then cooled to RT, satd. K2CO3 solution (100 ml) was added, and the mixture was washed with DCM. The organic phase was dried over Na2SO4 and then concentrated by evaporation to dryness. Purification was carried out by column chromatography on silica gel (DCM/methanol, 95:5+5% NH4OH [35%].

According to the analysis of related databases, 5049-61-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GRUENENTHAL GmbH; US2009/186899; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 848841-62-3, A common heterocyclic compound, 848841-62-3, name is 4-(6-Bromopyrazin-2-yl)morpholine, molecular formula is C8H10BrN3O, 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.

19b) 1-CHLORO-4- (6-MORPHOLIN-4-VL-PVRAZIN-2-YL)-ISOQUINOLINE A solution of 4-BROMO-1-CHLORO-ISOQUINOLINE (400 mg, 1.65 MMOL) in THF (20 mL) is cooled TO-72¡ãC. A solution of n-BuLi (2.5 M in hexanes) (0.80 mL, 2 MMOL) is added dropwise and the reaction temperature maintained AT-70 ¡ãC~-68¡ãC FOR 30min. ZnBr2 (408 mg, 1.91 MMOL) is dissolved in THF (6 mL) and is transferred to above mixture slowly at-70 ¡ãC. The solution is stirred 40 min at-70 ¡ãC, then warmed to room temperature by removing the cooling bath. Pd (PPh3) 4 (190 mg, 0.164 MMOL) in 6ML THF and 4-(6-BROMO-PYRAZIN-2-YL)- morpholine (400 mg, 1.65 MMOL) in THF (4 mL) are added to the reaction mixture dropwise, then the solution is heated to 60 ¡ãC for 30 min and then kept at rt overnight. The reaction mixture is diluted with ethyl acetate, washed with sat. NH4CI . then brine, and dried over sodium sulfate. The solution is concentrated until white solid came out from solution. The solid is collected by filtration, washed with ether and dried under vacuum. 300 mg of 1- CHLORO-4- (6-MORPHOLIN-4-YL-PYRAZIN-2-YL)-ISOQUINOLINE IS obtained. Yield was 56percent. MS/ESI+, M+1 = 327

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; NOVARTIS PHARMA GMBH; WO2005/28444; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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 – Synthesis of Intermediate Compound Int-6cA 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-6a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-6b, 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-Butyl lithium (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 provide 480 g of an orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil (mixture of Int-6c and Int-6c’). 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 to provide 190 grams of Compound Int-6c (60percent yield).

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.; ZENG, Qingbei; MAZZOLA, Robert, D., Jr.; YU, Wensheng; TANG, Haiqun; KIM, Seong Heon; TONG, Ling; ROSENBLUM, Stuart, B.; KOZLOWSKI, Joseph, A.; NAIR, Anilkumar Gopinadhan; WO2013/39876; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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. Computed Properties of C6H5Cl2N3O2

Example 3A – Synthesis of Synthesis of 3-amino-6-[4-(dimethylamino)phenyl]-5-{4- (methylsulfony.)phenyl]pyrazine-2-carboxylic acid; [00171] Step 1 : A mixture of methyl 3-amino-5, 6-dichloro-2-pyrazi?ecarboxylate (1.0 mmol, 222.0 mg), 4-(methyisulfo?yl) phenyl boronic acid (1.2 mmol, 240.0 mg), and tetrakis (triphenylphosphine) Pd (0) (0.12 mmol, 138.7 mg) in 50 ml of anhydrous dimethylformamide was mixed via inert conditions. A solution of potassium carbonate (5 mmoles, 691.1 mg) in deionized water (3 ml) was added to the reaction mixture and heated at 75 0C overnight under an argon atmosphere. The product was purified by reversed phase HPLC (5-75 acetonitrile with 0.1% trifluoroacetic acid at 50 mi/min on XBridge Prep C18 OBD 5um 30 x 150 mm. Retention time 5.9 min) and characterized by 1H and 13C NMR. 1 H NMR (500 MHz, DMSO-d6) delta 8.08 (dt apparent, J = 9.0 Hz1 2.0 Hz, 2H)1 delta 7.99 (dt apparent, J = 8.5 Hz1 1.5 Hz, 2H), delta 7.66 (bs, 2H), delta 3.30 (s, 3H). 13C NMR (125 MHz, DMSO-d6) delta 43.8 (s), delta 122.5 (s), delta 127.2 (s), delta 130.7 (s), delta 130.9 (s), delta 141.1 (s), delta 142.1 (s), delta 153.3 (s), delta 154.9 (S), delta 167.2 (s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1458-18-0, its application will become more common.

Reference:
Patent; MALLINCKRODT INC.; NEUMANN, William, L.; FRESKOS, John, N.; DORSHOW, Richard, B.; WO2010/121003; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem