Month: September 2021

Application of 75907-74-3, A common heterocyclic compound, 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, molecular formula is C8H12N2O, 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.

Take Ligustrazine 2· 176g (16mmol) dissolved into 20ml glacial acetic acid, add 1.8ml (16mmol) of 30% hydrogen peroxide at 90 C for 4h, and then supplement 1.8ml (16mmol) 30% hydrogen peroxide to continue the reaction for 2h, TLC monitoring reaction is complete, add an appropriate amount of sodium sulfite to neutralize excess hydrogen peroxide, the reaction solution was filtered, and the filtrate was cooled at room temperature, adjust the pH at 10 with 50% sodium hydroxide, extract with dichloromethane, collect the organic layer, dehydrate the saturated brine, dry over anhydrous sodium sulfate, and recover the solvent under reduced pressure, obtained white Ligustrazine mono-nitroxide compound crude (2). The crude product is added into 1.51ml (16mmol) of acetic anhydride, heating at 105 C for 2.5 h, after TLC was monitored until the reaction has completed, it was evaporated to get dryness under reduced pressure, obtained black slurry of ligustrazine acetylate (3). The next black slurry was placed in a solution of 20 ml (THF: Me0H: H20 = 3:1:1), add 1.92g (48mmol) sodium hydroxide in batches, the reaction was stirred for 2 h, extracted with dichloromethane and organic layer was collected, dehydrated with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent is recovered under reduced pressure and then obtained a crude hydroxyl Ligustrazine, that is re-crystallized from n-hexane, obtained 1.85g of yellow needle crystals (4), the yellow crystal of TMP-0H prepared in the previous step was dissolved into 20 ml of anhydrous tetrahydrofuran, after that add 3.03 g (15.9mmol) Tscl, 2.464 g (24.4mmol) TEA, 0.15 g (12.2mmol) DMAP, stir overnight, extract with methylene chloride, dehydrate the saturated brine, dry over anhydrous sodium sulfate, filter, recover solvent, obtained light yellow chloro-Ligustrazine crude product, appropriate amount of silica gel sample, separation on silica gel column [V (petroleum ether): V (ethyl acetate) = 10:1] and then obtained colorless and transparent chloro- Ligustrazine 1.86g, yield 90.3%.

The synthetic route of 75907-74-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Lei Pengcheng; Xu Bing; Wang Penglong; (31 pag.)CN108456239; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 33332-28-4, 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. 33332-28-4 name is 2-Amino-6-chloropyrazine, 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.

Following a literature procedure (Walters, I.A.S. Tetrahedron Lett. 2006, 47, 341), a solution of dimethylzinc (2.0 M in toluene, 75.0 mL, 150.0 mmol) was carefully added in 25 mL portions to a solution of 2-amino-6-chloropyrazine (10.0 g, 77.0 mmol) and l ,3-bis(diphenylphosphino)propane-nickel (II) chloride (4.2 g, 7.8 mmol) were dry in dioxane (400 mL) under a nitrogen atmosphere. The reaction was stirred at rt for 2 h and then heated to 50 0C for 1 h and 95 0C overnight. The reaction was allowed to cool to rt and an additional charge of dimethylzinc was added (22 mL, 44 mmol) and the reaction was then maintained at 95 0C overnight. The reaction was cooled to rt, quenched over 15 min with MeOH and then concentrated to a brown solid. Water and EtOAc were added to the solid, and the mixture was sonicated. The solid was removed by filtration and brine was added to the EtO Ac-water mixture. The layers were separated, and the organic layer was dried (Na2SO^, and concentrated to give 9.72 g (~70 purity) of 6-methylpyrazin-2-amine, which was carried forward without further purification: LCMS (m/z): 110.0 (MH+), R = 0.21 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; WO2009/115572; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, 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: C5H3ClN2O2

Preparation of (5-chloropyrazin-2-yl)(pyrrolidin-1-yl)methanone (SM-1):(SM-1 ) delta-chloropyrazine^-carboxylic acid (1 .00 gram, 6.31 mmol) in dichloromethane (30 ml_) was treated with catalytic amount of dimethylformamide, followed by (COCI)2 (0.85 ml_, 9.46 mmol). The resulting mixture was stirred over night. The reaction was concentrated and dried under vacuum to give desired delta-chloropyrazine^-carbonyl chloride as a solid (1 .05 g, 100%). delta-chloropyrazine^-carbonyl chloride (670mg, 3.79mmol) was dissolved in dichloromethane (1 OmL) and cooled to O0C. Thethylamine (1 .58ml_, 1 1 .4mmol) and pyrrolidine (0.32ml_, 3.79mmol) were then added successively drop-wise. Following the addition, the ice bath was removed and the reaction was allowed to warm to room temperature and stir for 1 hour. The reaction was then diluted with dichloromethane and washed with 1 N HCI, water, and brine. The organics were dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography eluting with 30 – 80% ethyl acetate in hexane afforded the desired (5-chloropyrazin- 2-yl)(pyrrolidin-1 -yl)methanone (SM-1 : 677.0mg, 84.5%). 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1 .86 – 1 .99 (m, 4 H),3.65 – 3.71 (m, 2 H), 3.73 – 3.79 (m, 2 H), 8.52 (d, J=1 .37 Hz, 1 H), 8.93 (d, J=1 .37 Hz, 1 H).

The synthetic route of 36070-80-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; CORBETT, Jeffrey Wayne; GUZMAN-PEREZ, Angel; PFEFFERKORN, Jeffrey Allen; TU, Meihua Mike; WO2010/103438; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, A new synthetic method of this compound is introduced below., HPLC of Formula: C5H4N4

To a suspension of 5-aminopyrazine-2-carbonitrile (414 mg, 3.44 mmol) in THF (10 mL) was added sodium hydride (230 mg, 5.73 mmol) at 0 C and the resulting mixture was then stirred at ambient temperature for 1 h. Compound 305-4 (1.0 g, 2.87 mmol) was added and stirred at 60 C for 4 h. The reaction mixture was quenched with ice water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated to afford the title compound 306-4 as a yellow solid (500 mg, 42% yield). LCMS:420.9 [M+1]. ?H NIVIR (400 1VIFIz, DMSO-d6): 2.36 (s, 3H), 3.35 (s, 3H), 3.77 (s, 3H), 5.21 (s, 2H), 5.68 (s, 1H), 6.86-6.88 (m, 2H), 8.63 (d, J 1.2 Hz, 1H), 8.86 (d, J1.2 Hz, 1H), 13.89 (s, 1H).

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; PHARMAENGINE, INC.; CAI, Xiong; QIAN, Changgeng; WANG, Yanong Daniel; (98 pag.)WO2017/132928; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 23611-75-8, 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. 23611-75-8, name is Methyl 6-chloropyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Example 15; 6-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-N-m-tolylpyrazine-2-carboxamide; Example 15A; 6-chloropyrazine-2-carboxylic Acid; The product from Example 1E (1.78 g, 10.3 mmol) was dissolved in EtOH (25 mL). 1M NaOH (25 mL) was added, and the reaction stirred at ambient temperature for 2 h. The reaction mixture was acidified to pH?3 with 1M HCl (aq). The mixture was then diluted with water (150 mL) and extracted with EtOAc (4×100 mL). The organic extracts were combined, washed with brine (100 mL), dried over Na2SO4, filtered and concentrated under vacuum to provide the title compound as a white solid (1.54 g, 94%). MS (DCI/NH3) m/z 176 (M+NH4)+.

The synthetic route of Methyl 6-chloropyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Abbott Laboratories; US2009/281118; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 32974-92-8, name is 1-(3-Ethylpyrazin-2-yl)ethanone, A new synthetic method of this compound is introduced below., name: 1-(3-Ethylpyrazin-2-yl)ethanone

(1) 2-acetyl-3-ethylpyrazine (420 ul, 3 mmol) was dissolved in methanol (20 ml).After dissolution,Add 4,4-dimethyl-3-thiosemicarbazide (360 mg, 3 mmol),well mixed,The mixed solution was refluxed at 65 C for 4 h.filter,The filtrate is volatilized at room temperature.There are pale yellow crystals,Filter again,Wash 2-3 times with absolute ethanol,Obtaining a ligand L4;

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; Guangxi Normal University; Yang Feng; Sun Zewen; Zhao Lei; Liang Hong; (16 pag.)CN109796501; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 36070-75-4, name is 5-Chloropyrazine-2-carbonitrile, 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 36070-75-4, COA of Formula: C5H2ClN3

1-((2S,4/?)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1 (2/-/)-yl)ethanone (for a preparation, see Intermediate 1 ) (50 mg, 0.177 mmol), 5-chloropyrazine-2-carbonitrile (37.0 mg, 0.265 mmol) and DIPEA (0.123 mL, 0.706 mmol) were combined in NMP (1 .5 mL) and heated in a sealed flask under microwave irradiation to 200C for 1 h. The mixture was partitioned between water (150 mL) and EtOAc (4×100 mL). The organic layers were combined, washed with brine (2×100 mL), dried by passing through a hydrophobic frit, and concentrated in vacuo. The resulting residue was purified by chromatography (25 g column, EtOAc/cyclohexane gradient) to give 5-(((2S,4/?)-1-acetyl- 6-bromo-2-methyl-1 ,2,3,4-tetrahydroquinolin-4-yl)amino)pyrazine-2-carbonitrile (61 mg, 0.158 mmol, 89 % yield) as a brown gum.LCMS (Formate, 2 min), Rt = 0.94 mins, MH+ = 386/388.

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-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXOSMITHKLINE LLC; AMANS, Dominique; DEMONT, Emmanuel Hubert; MITCHELL, Darren Jason; SEAL, Jonathan Thomas; WO2012/143415; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 63744-22-9, 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. 63744-22-9 name is 6,8-Dibromoimidazo[1,2-a]pyrazine, 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 mixture of 3,4-dimethoxyaniline (18.0 g, 118 mmol), 6,8- dibromoimidazo[1 ,2-a]pyrazine (25.0 g, 90.4 mmol), and Lambda/,Lambda/-diisopropylethylamine (11.7 g, 90.4 mmol) in DMF (500 ml_) was stirred at 120 0C overnight. After this time, the reaction was cooled to room temperature and concentrated to approximately 100 ml_ under reduced pressure. The dark brown reaction mixture was poured into ice-cold water (300 ml_) and stirred for 10 min. The resulting brown precipitate was filtered and the filter cake washed with water (100 ml_). The filter cake was dried under vacuum and recrystallization from methanol (-800 ml_) to afford 6-bromo-Lambda/-(3,4,5- trimethoxyphenyl)imidazo[1 ,2-a]pyrazin-8-amine (2) (23.3 g, 74%) as a light brown needle-shaped solid: 1H NMR (300 MHz, DMSO-Gf6) 9.81 (s, 1 H), 8.22 (s, 1 H), 7.93 (s, 1 H), 7.75 (d, J = 2.4 Hz, 1 H), 7.62 (s, 1 H), 7.53 (dd, J= 8.7, 2.4, 1 H), 6.94 (d, J= 8.7 Hz, 1 H), 3.77 (s, 3H), 3.75 (s, 3H); ESI MS m/z 349.2 [M + H]+; HPLC, 6.92 min, >99% (AUC).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6,8-Dibromoimidazo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; CGI PHARMACEUTICALS, INC.; MITCHELL, Scott A.; CURRIE, Kevin S.; BLOMGREN, Peter A.; KROPF, Jeffrey E.; LEE, Seung H.; XU, Jianjun; STAFFORD, Douglas G.; HARDING, James P.; BARBOSA, Jr., Antonio J.; ZHAO, Zhongdong; WO2010/68257; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 14508-49-7, name is 2-Chloropyrazine, 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 14508-49-7, category: Pyrazines

The product of preparation 16 (83mg, 0.32mmol), 2-chloropyrazine (36mg, 0.31 mmol), sodium tert-butoxide, (36mg, 0.37mmol), Pd2(dba)3 (7mg, 8mumol) and BINAP (22mg, 35mumol) were suspended in tert-butanol (2mL) and the mixture was heated at 110C in the microwave for 3 hours. The mixture was replenished with further amounts of 2-chloropyrazine (36mg, 0.31 mmol), sodium tert-butoxide (36mg, 0.37mmol), Pd2(dba)3 (7mg, 8mumol) and BINAP (22mg, 30mumol) at hourly intervals. The reaction mixture was then azeotroped with methanol and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate:methanol: 0.88 ammonia, 100:0:0 to 90:10:1. This was followed by further purification by column chromatography on Biotage amino silica gel, eluting with pentane:ethyl acetate, 100:0 to 0:100, to afford the title compound as a colourless oil in 76% yield, 80mg. 1HNMR(CDCl3, 400MHz) delta: 1.70-1.90(m, 4H), 1.91-2.04(m, 2H), 2.47-2.63(m, 6H), 2.93-3.02(m, 2H), 3.90-3.98(m, 2H) 4.28-4.35(m, 2H), 4.63(s, 2H), 6.60(d, 1H), 7.37(d, 1H), 7.85(m, 1H), 8.10(m, 1H), 8.21(m,1H) MS APCI+ m/z 340 [MH]+ Micro analysis found (%); C(67.21), H(7.46), N(20.60); C19H25N5NO requires (%); C(67.31), H(7.42), N(20.63)

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

Reference:
Patent; Pfizer Limited; EP1595881; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H3Br2N3

A solution of intermediate 1-01(15 g, 59.3 mmol) inmorpholine (15 ml, 178 mmol) was heated at 120 C. in a Parr reactor for 48 h. A brown solid appears. The solid was suspended in DCM and washed with NaHCO3 aq. sat (twice). The organic phase was dried (NaSO4), filtered and evaporated to dryness to obtain 1-02, 14.8 g of a brown solid(Y: 96%)

The synthetic route of 24241-18-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO); Serrano Marugan, Manuel; Pastor Fernandez, Joaquin; Martinez Gonzalez, Sonia; Ortega Molina, Ana; Bischoff, James R.; Oyarzabal Santamarina, Julen; (220 pag.)US9993554; (2018); B2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem