Author: Jessica.F

Synthetic Route of 313339-92-3, 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. 313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

A solution of BnOH (30.8 g, 0.285 mol, 29.6 mL, 1.1 eq) in THF (450 mL) was cooled to 0 C. NaH (12.4 g, 0.311 mol, 60% oil dispersion, 1.2 eq) was added slowly to the mixture at 0 C. After addition, the mixture was stirred at 25C for 1 hr. The resultant solution was added a solution of 3,5-dichloropyrazine-2-carbonitrile (45.0 g, 258.64 mmol, 1.0 eq) in THF (450 mL) at -78 C and the mixture was stirred at -78 C for 0.5 hr. The reaction was then poured into water (1.00 L) and extracted with EtOAc (1.00 L*3). The combined organic layer was washed with brine (500 mL), dried over Na2S04, filtered and concentrated. The residue was slurryed in petroleum ether/EtOAc = 10: 1 (1.50 L) at 25 C for 0.5 hr. The mixture was filtered and the filter cake was washed with petroleum ether (200 mL). The filter cake was dried under reduced pressure to give 5-(benzyloxy)-3- chloropyrazine-2-carbonitrile (79.3 g, 300 mmol, 58% yield, 93% purity) as a white solid. LCMS m/z [M+H]+ = 245.9. 1H NMR (400MHz CDCl3) d 8.23 (s, 1H), 7.51 – 7.39 (m, 5H), 5.48 (s, 2H).

The synthetic route of 3,5-Dichloropyrazine-2-carbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RELAY THERAPEUTICS, INC.; D.E. SHAW RESEARCH, LLC; TAYLOR, Alexander, M.; LESCARBEAU, Andre; KELLEY, Elizabeth, H.; SHORTSLEEVES, Kelley, C.; WALTERS, W., Patrick; MURCKO, Mark, Andrew; MCLEAN, Thomas, H.; GUNAYDIN, Hakan; GIORDANETTO, Fabrizio; THERRIEN, Eric; (607 pag.)WO2019/183367; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 6863-73-6, name is 3-Chloropyrazin-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. Quality Control of 3-Chloropyrazin-2-amine

Bromoacetaldehyde diethyl acetal (17.4 ml, 115.8 mmol) was added dropwise to a 48% aqueous solution of hydrobromic acid (4.45 ml, 38.6 mmol) at RT. The mixture was stirred at reflux temperature for 2 h. and then poured onto a suspension of sodium hydrogen carbonate (74.5 g, 0.88 mol) in isopropanol (220 ml). The mixture was stirred for a further 30 min. and then filtered off. 3-Chloro-pyrazin-2-ylamine (5 g, 38.6 mmol) was added to the filtrate and the mixture was stirred at 85 C for 4 h. The solvent was evaporated in vacuo and the crude product suspended in a saturated solution of sodium hydrogen carbonate and extracted with DCM. The organic layer was dried (Na2S04), filtered and the solvents evaporated in vacuo. The crude product was precipitated from Et20 to yield intermediate 3 (4.1 g, 70%) as a brown solid which was used in the next step without further purification.

The synthetic route of 3-Chloropyrazin-2-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BARTOLOME-NEBREDA, Jose, Manuel; CONDE-CEIDE, Susana; MACDONALD, Gregor, James; PASTOR-FERNANDEZ, Joaquin; VAN GOOL, Michiel, Luc, Maria; MARTIN-MARTIN, Maria, Luz; VANHOOF, Greta, Constantia, Peter; WO2011/110545; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 24241-18-7, 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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Preparation of Intermediate I-02. A solution of intermediate I-01(15 g, 59.3 mmol) in morpholine (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 2-Amino-3,5-dibromopyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Centro Nacional De Investigaciones Oncologicas (CNIO); US2012/83492; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 13924-95-3, name is Methyl 5-hydroxypyrazine-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. Recommanded Product: 13924-95-3

Fluoromethyl toluene-4-sulfonate (Journal of Labelled Compounds & Radiopharmaceuticals, 46 (6), 555-566; 2003) (344 mg) and cesium carbonate (824 mg) were added to a solution of methyl 5-hydroxypyrazine-2-carboxylate (130 mg) in N,N-dimethylformamide (2.0 mL). The reaction solution was stirred at 70 C. for five hours and 30 minutes and then cooled to room temperature. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography to obtain the title compound (18.0 mg).1H-NMR (400 MHz, CDCl3) delta (ppm): 4.03 (s, 3H), 6.14 (d, J=51.2 Hz, 2H), 8.42 (d, J=1.2 Hz, 1H), 8.94 (d, J=1.2 Hz, 1H).

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

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD.; US2010/93999; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 41110-28-5,Some common heterocyclic compound, 41110-28-5, name is 3-Methylpyrazine-2-carboxylic acid, molecular formula is C6H6N2O2, 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 3-methylpyrazinecarboxylic acid (Vishweshar, J. Org. Chem. 2002, 67, 556) (3.2 mL, 30 mmol) in ethanol (20 mL) was saturated with hydrogen chloride and stirred at 70 C. for 16 hours. The solution was concentrated, the residue was taken up in chloroform and the solution was washed with 1 N sodium hydroxide and brine, dried over magnesium sulfate and concentrated to dryness, leaving a brown solid (828 mg, 66%)

The synthetic route of 41110-28-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc; US2005/234065; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1111638-10-8, name is 3-Chloro-5H-pyrrolo[2,3-b]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. Quality Control of 3-Chloro-5H-pyrrolo[2,3-b]pyrazine

A solution of 3-chloro-5H-pyrrolo[2,3-b]pyrazine (20 g, 131 mmol) and DIPEA (37 mL, 212 mmol) in NMP (100 mL) was stirred with cooling provided by a salt/ice-bath. 2-(Trimethylsilyl)ethoxymethyl chloride (28.3 mL, 160 mmol) in NMP (40 mL) was added over a period of 5-10 mm. The cooling bathwas removed, and the mixture stirred overnight at RT. A 5% aq. LiCI solution (100 mL) was added. EtOAc (400 mL) was added and the mixture transferred to a 2 L separating funnel. The aqueous layer was removed and the EtOAc layer was washed with further 5% aq. LiCI solution (3 x 100 mL). The EtOAc layer was then washed successively with 0.5 M aq. KHSO4 (2 x 100 mL), sat. aq. Na2CO3 (50 mL), 5% aq. LiCI (50 mL) and sat. brine solution (100 mL). The EtOAc layer was dried (MgSO4), filteredand evaporated, to give a dark oil. The residue was purified by column chromatography on silica gel (gradient elution, 0-50%, EtOAc/petrol), to give the title compound (31.8 g), MS: [M+H] = 284.

The synthetic route of 1111638-10-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; TAIHO PHARMACEUTICAL CO., LTD.; JOHNSON, Christopher Norbert; BUCK, Ildiko Maria; CHESSARI, Gianni; DAY, James Edward Harvey; FUJIWARA, Hideto; HAMLETT, Christopher Charles Frederick; HISCOCK, Steven Douglas; HOLVEY, Rhian Sara; HOWARD, Steven; LIEBESCHUETZ, John Walter; PALMER, Nicholas John; ST DENIS, Jeffrey David; TWIGG, David Geoffrey; WOODHEAD, Andrew James; (377 pag.)WO2019/167000; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 61655-77-4, name is 2-Chloro-6-(4-methylpiperazin-1-yl)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 61655-77-4, HPLC of Formula: C9H13ClN4

EXAMPLE 87: 5-(6-(4-methylpiperazin-l-yl)pyrazin-2-yl)-lH-pyrrolor2,3-b1pyridineThe starting material 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrrolo[2,3-b]pyridine (124) (50 mg, 0.2 mmol, 1 eq) and 2-chloro-6-(4-methylpiperazin-l-yl)pyrazine (63) (44 mg, 0.2 mmol, 1 eq) in DMF (5 mL) was degassed and purged under argon atmosphere for 10 min. To this reaction mixture was charged Cs2C03 (133 mg, 0.4 mmol, 2 eq) followed by addition of Pd(PPh3)4 (0.01 mg, 0.04 mmol) and degassing and purging under argon for an additional 10 min. The reaction mixture was heated at 100C for 12 h in a sealed tube. After completion of the reaction, the reaction mixture was diluted with CHC13 and filtered through Celite. The solvents were distilled off and the crude material was submitted for flash column purification in neutral alumina using 2% MeOH/CHCl3 to obtain pale yellow solid compound 5-(6-(4- methylpiperazin-l-yl)pyrazin-2-yl)-lH-pyrrolo[2,3-b]pyridine 125 in 20 mg quantity. The compound 125 was confirmed by 1HNMR and LCMS. 1H NMR (400 MHz, CDC13) delta: 8.96 (d, J=1.5Hz 1H), 8.55 (d, J=1.70Hz, 1H), 8.30 (s, 1H), 8.08 (s,lH), 7.35 (m, J=3.04, 1H), 6.60(m, J=1.95 1H), 3.75 (m, J=5.00, 4H), 2.58 (m, J=5.12, 4H), 2.38 (s , 3H); MS m/z 294.9 (M+H)+.

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, 2-Chloro-6-(4-methylpiperazin-1-yl)pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARRIEN PHARMAEUTICALS LLC; VANKAYALAPATI, Hariprasad; APPALANENI, Rajendra, P.; REDDY, Y., Venkata Krishna; WO2012/135631; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 32111-21-0, 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. 32111-21-0, name is 2-Iodopyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Pd2(dba)3 -CHCl3 (5 mg, 0.5 mol %), 2′-(dicyclohexylphosphino)biphenyl-2-amine (8 mg, 2 mol %) and sodium tert-butoxide (13 mg, 0.14 mmol) were weighed in air and transferred into flask, followed by dioxane (750 muL), 1 ‘-(piperidin-4- yl)spiro[benzo[d][l,3]oxazine-4,4’-piperidin]-2(lH)-one bis-hydrochloride (compound no. 49) (37 mg, 0.10 mmol) and iodopyrazine (viia). (20.6 mg, 0.10 mmol). The flask was flushed with nitrogen and stirred at 800C for 16 hours. The reaction mixture was diluted with methanol (500 muL), filtered (Whatman 0.45 mum PTFE) and subjected to reverse-phase HPLC purification (2-25% CH3CN gradient [w/ 0.1% TFA (aq)] over 10 minutes, 1.0 mL injected, 35 mL/min) to provide l’-(l-(pyrazin-2-yl)piperidin-4- yl)spiro[benzo[d][l,3]oxazine-4,4′-pirhoeridin]-2(lH)-one (compound no. 74). LC/MS m/z 380.2 [M+H]+, retention time 1.35 min (RP-Cl 8, 10-99% CH3CN/0.05% TFA).

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

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/21375; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1082843-70-6, name is 3,5-Dibromo-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 1082843-70-6, Product Details of 1082843-70-6

[0955] Into a 250 mL sealed tube was placed compound90d (50.0 g, 184 mmol) andNH40H (150mL). The resultingmixture was stirred overnight at 100 C. Uponcooling, a solidwas collected by filtration and dried in an oven under reducedpressure to obtain the compound 90e as a grey solid (28.0 g,66% yield), which was used in next step without furtherpurification.

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; JANSSEN PHARMACEUTICA, NV; Player, Mark R.; Meegalla, Sanath K.; Illig, Carl R.; Chen, Jinsheng; Wilson, Kenneth J.; Lee, Yu-Kai; Parks, Daniel J.; Huang, Hui; Patel, Sharmila; Lu, Tianbao; US2014/364414; (2014); 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. 56423-63-3, name is 2-Bromopyrazine, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Bromopyrazine

Crystals of 2 were obtained by the slow-diffusion method between 3 layers: 1st layer is a solution of Fe(OTs)2*6H2O(0.096 g, 0.2 mmol, 1 equiv.) and NH4SCN (0.030 g, 0.4 mmol, 1 equiv.) in a water/methanol mixture (1/1, 10 ml); 2nd one is a water/methanol mixture (1/1, 10 ml); 3rd one is a solution of 2-bromopyrazine (0.127 g, 0.8 mmol, 1 equiv.) in methanol (3 ml). After 2 weeks red plates grew in the second layer; they were collected, washed with water and dried in air. Yield is 0.050 g (50%). Anal. Calc. for Fe1C18H16O2N10S2Br4: C, 25.59; H, 1.90; N, 16.58; S,7.58. Found: C, 24.91; H, 1.77; N, 16.42; S, 7.67%. Principal IR absorption bands for 2 (cm-1): 2080 (s), 1510 (m), 1456 (m),1381 (s), 1130 (s), 1057 (m), 1056 (m), 1020 (s).

The synthetic route of 56423-63-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Shylin; Gural Skiy; Bykov; Demeshko; Dechert; Meyer; Hauka; Fritsky; Polyhedron; vol. 87; (2015); p. 147 – 155;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem