Pyrazines

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. 179323-60-5, name is 1-(Pyrazin-2-yl)ethanamine, A new synthetic method of this compound is introduced below., Application In Synthesis of 1-(Pyrazin-2-yl)ethanamine

Step B: 2-[1-(Pyrazin-2-yl)ethylamino]-4-[benzimidazol-1-yl]pyrimidine The title compound was prepared from 1-(pyrazin-2-yl)ethylamine according to the procedure outlined in the EXAMPLE 1, Step C. Mass spectrum 318.2 (M+1).

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; Merck & Co., Inc.; US6498165; (2002); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 113305-94-5, 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. 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a stirred mixture of 5-aminopyrazine-2-carbonitrile (542 mg, 4.5 mmol) in THF (20 mL) was slowly added sodium hydride (240 mg, 6.02 mmol) below 15 C. The resulting mixture was stirred at room temperature for 1 hour and compound 106 (1 .0 g, 3.01 mmol) was added. The reaction mixture was stirred at 60 C for 4 hours, quenched with ice-water and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated to afford the title compound 107 (1.0 g, crude) as a yellow solid, which was used for the next step without further purification.

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

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

Application of 56423-63-3, These common heterocyclic compound, 56423-63-3, name is 2-Bromopyrazine, 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: Reactions were carried out in a Bohdan XT 24 position block using the appropriate halide indicated.2M Sodium carbonate (0.680 mL, 1.36 mmol) was added to a stirred mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (10, 151 mg, 0.62 mmol), the appropriate halide (0.74 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Pd(Amphos)Cl2) (26.3 mg, 0.04 mmol) in DME (4 mL) under nitrogen. The resulting mixture was stirred at 80 C for 4 h, allowed to cool, diluted with water (10 mL), extracted with EtOAc (2¡Á25 mL) and the organic layer was evaporated to afford crude products. Unless otherwise stated the crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5 mu silica, 19 mm diameter, 100 mm length, 5-95% MeCN/1% NH3 in H2O).

Statistics shows that 2-Bromopyrazine is playing an increasingly important role. we look forward to future research findings about 56423-63-3.

Reference:
Article; Bethel, Paul A.; Campbell, Andrew D.; Goldberg, Frederick W.; Kemmitt, Paul D.; Lamont, Gillian M.; Suleman, Abid; Tetrahedron; vol. 68; 27-28; (2012); p. 5434 – 5444;,
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. 54608-52-5, name is 2-Hydrazinopyrazine, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H6N4

Example 1. Preparation of Selinexor Lot No.1305365 (Form A). Selinexor for Lot No. 1305365 was made in accordance with the following reaction scheme: A solution of propane phosphonic acid anhydride (T3P, 50% in ethyl acetate, 35Kg) in THF (24.6Kg) was cooled to about -40 C. To this solution was added a solution of KG1 (13.8Kg) and diisopropylethylamine (12.4Kg) in tetrahydrofuran (THF, 24.6Kg). The resulting mixture was stirred at about -40C for approximately 2.5 hours. In a separate vessel, KJ8 (4.80Kg) was mixed with THF (122.7Kg), and the resulting mixture cooled to about -20C. The cold activated ester solution was then added to the KJ8 mixture with stirring, and the reaction was maintained at about -20C. The mixture was warmed to about 5C, water (138.1Kg) was added and the temperature adjusted to about 20C. After agitating for about an hour, the lower phase was allowed to separate from the mixture and discarded. The upper layer was diluted with ethyl acetate (EtOAc). The organic phase was then washed three times with potassium phosphate dibasic solution (~150Kg), then with water (138.6Kg). The resulting organic solution was concentrated under reduced pressure to 95L, EtOAc (186.6Kg) was added and the distillation repeated to a volume of 90L. Additional EtOAc (186.8Kg) was added and the distillation repeated a third time to a volume of 90L. The batch was filtered to clarify, further distilled to 70L, then heated to about 75C, and slowly cooled to 0 to 5C. The resulting slurry was filtered and the filter cake washed with a mixture of EtOAc (6.3Kg) and toluene (17.9Kg) before being dried in a vacuum oven to provide selinexor designated Lot No. 1305365 (Form A).

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KARYOPHARM THERAPEUTICS INC.; AUSTAD, Brian Clinton; ROE, David, G.; (140 pag.)WO2016/25904; (2016); 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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, A new synthetic method of this compound is introduced below., Safety of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

Intermediate 1 (0.030 g, 0.080 mmol) was diluted with THF (2.0 ml) then charged with 3-(trifluoromethyl)-5 ,6,7,8-tetrahydro-[ 1 ,2,4]triazolo [4,3-a]pyrazine (0.031 g, 0.161 mmol). Reaction was heated to 50 C and stirred for 1 hour. At this time, the LC/MS did not show product forming – therefore, at this time TEA (0.056 ml, 0.40 1 mmol) was added and the resulting reaction mixture was heated to 80 C overnight. In the morning, clean reaction was detected by LC/MS. The crude reaction was concentrated and purified using Si02 chromatography employing a 0-50% (7:1 ACN/MeOH) in DCM gradient to deliver the desired material as a white solid (32 mg, 72%).1H-NMR (400 MHz, DMSO-d6) oe 9.08 (d, 1H), 8.43 (d, 1H), 7.62 (s, 1H), 7.30 (dd, 1H), 7.23 (d, 1H), 7.19 (t, 1H), 7.07 (t, 1H), 6.81 (t, 1H), 5.89 (s, 2H), 5.24 (s, 2H), 4.33-4.25 (m, 4H).

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

Reference:
Patent; NAKAI, Takashi; MOORE, Joel; PERL, Nicholas Robert; IYENGAR, Rajesh R.; MERMERIAN, Ara; IM, G-Yoon Jamie; LEE, Thomas Wai-Ho; HUDSON, Colleen; RENNIE, Glen Robert; JIA, James; RENHOWE, Paul Allen; BARDEN, Timothy Claude; YU, Xiang Y; SHEPPECK, James Edward; IYER, Karthik; JUNG, Joon; WO2014/144100; (2014); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486424-37-7, 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 486424-37-7 as follows.

A mixture of 3-amino-6-bromopyrazine-2-carboxylic acid (3.90 mmol, 1.1 equiv), 3-(methylsulfonamido)phenylboronic acid (1.0 equiv), sodium carbonate (5.0 equiv) and Pd(PPh3)4 (10 mol %) were sequentially added in 30 mL 4:1 (v/v) degassed dioxane-water. The reddish brown mixture was stirred under Ar for 2 min at room temperature before heating to 88 C. for 2.5 hours. The mixture was slowly acidified by adding 30 mL of 10% citric acid until pH=4. The mixture was cooled to 25-30 C., diluted with 40 mL ethyl acetate, then 20 mL water and transferred to a separatory funnel. The aqueous layer was removed, extracted with ethyl acetate (3¡Á10 mL), the combined organic layers were washed with water (2¡Á20 mL) and brine (3¡Á20 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide compound 181 as yellow solid which was washed with methylene chloride and used directly in the next step. ESI-MS m/z: 309.3 [M+H]+.

According to the analysis of related databases, 486424-37-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Intellikine LLC; Infinity Pharmaceuticals, Inc.; CASTRO, Alfredo C.; CHAN, Katrina; EVANS, Catherine A.; JANARDANANNAIR, Somarajannair; LESCARBEAU, Andre; LI, Liansheng; LIU, Tao; LIU, Yi; REN, Pingda; SNYDER, Daniel A.; TREMBLAY, Martin R.; US2013/267521; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1209459-10-8, 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. 1209459-10-8, name is 2-Bromo-5-fluoropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: A suspension of 2-(4- cyclopropyl-1 H-imidazol-1-yl)-9-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-7,8-dihydro- [1 ,4]diazepino[7,1-a]isoquinolin-5(4H)-one (100 mg, 0.225 mmol), 2-bromo-5-fluoropyrazine (90 mg, 0.51 mmol) and Pd(PPh3)4 (39 mg, 0.034 mmol) in DME (2.8 mL) was treated with a 2M aq. solution of Na2C03 (0.6 mL, 1.12 mmol). The mixture was heated to 90 C for 2h, allowed to cool to RT and poured onto H20. The mixture was extracted with DCM and the combined org. layers were washed with brine, dried over Na2S04, filtered and concentrated in vacuo. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent: 25% EtOAc in heptane for 2 min, then from 25% EtOAc in heptane to 100% EtOAc in heptane in 10 min, 100% EtOAc in heptane for 5 min) to yield a solid which was crystallized from diethyl ether and afforded the title compound (57 mg). UPLC-MS: MS 415.2 (M+H+); UPLC rt 0.92 min. 1H NMR (400 MHz, DMSO-d6) 8 ppm 0.59 – 0.69 (m, 2 H), 0.72 – 0.82 (m, 2 H), 1.75 – 1.86 (m, 1 H), 2.97 (t, J=5.62 Hz, 2 H), 3.70 (t, J=6.1 1 Hz, 2 H), 4.24 (br. s., 2 H), 7.15 (s, 1 H), 7.43 (s, 1 H), 7.54 (t, J=7.82 Hz, 1 H), 7.69 (d, J=7.58 Hz, 1 H), 8.01 – 8.16 (m, 2 H), 8.58 (s, 1 H), 8.83 (d, J=8.31 Hz, 1 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-Bromo-5-fluoropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; BEHNKE, Dirk; CARCACHE, David; ERTL, Peter; KOLLER, Manuel; ORAIN, David; WO2014/30128; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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.

Intermediate Example 1 -1 :Preparation of 6,8-dibromo-imidazo[1 ,2-a]pyrazineTo a stirred suspension of 2-amino-3,5-dibrompyrazine (427 g, 1688mmol) in water (6.4 L) / THF (482 ml_), at rt was added bromacetaldehyde-diethylacetal (998 g, 5065 mmol) in one portion. After stirring under reflux for 4 h, the clear orange solution was stirred for an additional 15 h at rt. The suspension was filtered, and the remaining solid was washed with MeOH (2 L) and dried in vaccuo at 60 C to yield 6,8-dibromo-imidazo[1 ,2-a]pyrazine as an off-white solid (500 g, 107% with residual MeOH): 1H-NMR (300 MHz, d6-DMSO): delta =9.02 (s, 1 H), 8.23 (d, 1 H), 7.89 (d, 1 H) ppm. UPLC-MS: RT = 0.80 min; m/z 277.9 [MH+]; required MW = 276.9.

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

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80230; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 78342-42-4, A common heterocyclic compound, 78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, molecular formula is C9H16N2O2, 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.

To a solution of 3.32 g (18 mmol) of commercially available (2S)-2, 5- dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at-70 ¡ãC was added 12 mL (19 mmol) of a 1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (19.5 mmol) of 2-fluoro-4- trifluoromethylbenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3 h before warming the reaction to ambient temperature. The reaction was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-5percent ethyl acetate in hexanes) afforded 5.5 g of the title compound. [1H NMR] (500 MHz, [CDCL3)] [8] 7.33- 7.25 (m, 3H), 4.35-4. 31 (m, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.60 (t, [1H,] J = 3.4 Hz), 3.33 (dd, 1H, J = 4.6, 13.5 Hz), 3.03 (dd, [1H,] J = 7,13. 5 Hz), 2.25-2. 15 (m, [1H),] 1.0 (d, 3H, J = 7 Hz), 0.66 (d, 3H, J = 7 Hz).

The synthetic route of 78342-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2004/7468; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 5521-58-4, A common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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.

3-{[5-(Azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]-N-(5-methylpyrazin-2-yl)benzamide To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1.0 eq), and acetonitrile (10 vols) followed by pyridine (3 eq) under a nitrogen atmosphere. Thionyl chloride (1.2 eq) as a solution in acetonitrile (0.225 vols) was added slowly, drop-wise via syringe pump over at least 2 hours. 5-Methylpyrazin-2-amine (1.2 eq) was added to the mixture as a solid. After 2.5 hours the reaction was quenched by adding toluene (10 vols) and 1.0M sodium carbonate solution (2.5 eq). The layers were separated. The organic layer was retained in the flask, then 1.0M hydrochloric acid (1.94 eq) was added. The mixture was agitated for 15 minutes then separated. The organic layer was washed with two aliquots of water (5 vols) then the solvent was removed on the rotary evaporator. Toluene (5 vols) was added to the residue, and warmed to 45 C. Isohexane (1.7 vols) was added, the mixture was seeded, and allowed to cool to ambient temperature overnight. The mixture was cooled to 0 C. for 4 hours, and then cooled to -10 C. for 3 hours. The solid was isolated by filtration then washed with isohexane (2.5 vols). After drying in the vacuum oven at 40 C. overnight, the desired product was obtained as a solid (corrected yield 85%).

The synthetic route of 5521-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AstraZeneca AB; US2010/210621; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem