Category: Pyrazines

Electric Literature of 4745-93-1, The chemical industry reduces the impact on the environment during synthesis 4745-93-1, name is 5H-Pyrrolo[2,3-b]pyrazine, I believe this compound will play a more active role in future production and life.

Example 4; Synthesis of propane-1-sulfonic acid [2,4-difluoro-3-(5H-pyrrolo[2,3-b]pyrazine-7-carbonyl)-phenyl]-amide P-0001; Propane-1-sulfonic acid [2,4-difluoro-3-(5H-pyrrolo[2,3-b]-pyrazine-7-carbonyl)-phenyl]-amide P-0001 was prepared in two steps from 5H-pyrrolo[2,3-b]pyrazine 3 as shown in Scheme 2.; Step 1-Preparation of propane-1-sulfonic acid 2,4-difluoro-3-[hydroxy-(5H-pyrrolo[2,3-b]pyrazin-7-yl)-methyl]-phenyl-amide (9); To 5H-pyrrolo[2,3-b]pyrazine (3, 0.150 g, 1.26 mmol) and propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (8, 0.388 g, 1.47 mmol), 2.2 mL of methanol was added. This suspension was allowed to stir for 10 minutes, followed by the addition of potassium hydroxide (0.230 g, 4.10 mmol). The reaction was allowed to stir at room temperature for 7 hours, then poured into 5 mL of water and 5 mL of saturated ammonium chloride and extracted with 5 mL of ethyl acetate. The organic layer was separated and concentrated under vacuum, and the resulting residue was purified by silica gel column chromatography eluting with a gradient of 10 to 100% ethyl acetate in hexanes. Appropriate fractions were combined and concentrated under vacuum to give the desired compound (9, 243 mg). MS (ESI)[(M-18)+H+]+=365.1.

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, 5H-Pyrrolo[2,3-b]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Ibrahim, Prabha N.; Spevak, Wayne; Cho, Hanna; US2009/306087; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 33332-25-1, 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of methyl 5-chloropyrazine-2-carboxylate (8.00 g, 46.40 mmol) in THF (100 mL) was added NaBH4 (3.51 g, 93.00 mmol) under nitrogen atmosphere and the reaction mixture was stirred at 0 C for 5 h. The reaction was quenched with water (200 mL) and extracted with ethyl acetate ( 3 x 200 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Redisep-40 g, 30-40% EtOAc/n-hexane) to obtain Intermediate 112A (2.00 g, 29.80%) as a yellow solid.1H NMR (300 MHz, DMSO-d6) delta ppm 4.64 (d, J = 5.67 Hz, 2 H), 5.68 (t, J = 5.85 Hz, 1 H), 8.53 (s, 1 H), 8.72 (d, J = 1.13 Hz, 1 H). LCMS (Method-H ): retention time 0.476 min, [M+H] 145.2.

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; GUNAGA, Prashantha; BHIDE, Rajeev S.; BORA, Rajesh Onkardas; PANDA, Manoranjan; YADAV, Navnath Dnyanoba; PRIESTLEY, Eldon Scott; RICHTER, Jeremy; (321 pag.)WO2018/93569; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 36070-80-1, 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

In a 2L stainless steel autoclave,Add 317 g (2.0 mol) of 5-chloropyrazine-2-carboxylic acid, cooling to 0 ~ 10 C, adding anhydrous hydrogen fluoride 480g (24mol),The temperature was further lowered to -40 C, and sulfur tetrafluoride 476 (4.4 mol) was introduced.Then, the temperature was slowly raised to 75 to 80 C, and the reaction was kept for 6 hours.At the end of the reaction, the reaction hydraulic pressure is poured into the ice water.Neutralize to pH=7 with 10% aqueous sodium carbonate solution.The organic layer is separated and steamed,The obtained product was subjected to rectification to obtain 329 g of 2-chloro-5-trifluoromethylpyrazine in an amount of 99%.The yield was 90%.

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

Reference:
Patent; Jinkai (Liaoning) Chemical Co., Ltd.; Li Degang; Wang Yongcan; Fu Limin; Tang Xiaofeng; Qi Yue; Sun Jie; Yang Yang; Zhang Wei; (6 pag.)CN107840828; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 274-79-3, A common heterocyclic compound, 274-79-3, name is Imidazo[1,2-a]pyrazine, molecular formula is C6H5N3, 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: Imidazo[1,2-a]pyrazines (0.3 mmol), 2-chlorobenzaldehyde (0.33 mmol, 1.1 equiv.), K2CO3 (0.9 mmol, 3 equiv.), PivOH (30 mol%), Pd(OAc)2 (7.5 mol %), and Xantphos (15 mol %) were added to a 10 mL round-bottomed flask, and then a mixed solvent of 3 mL of DMF and 30 uL of H2O was added. The mixture was stirred under air at 110 C for 24 h. After the reaction was complete, the mixture was washed with water and extracted with ethyl acetate three times. The combined organic layer was dried with anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using dichloromethane/methanol as the eluent to give the pure product.

The synthetic route of 274-79-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Mu, Bing; Li, Jingya; Zou, Dapeng; Wu, Yusheng; Chang, Junbiao; Wu, Yangjie; Tetrahedron Letters; vol. 58; 52; (2017); p. 4816 – 4821;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 486424-37-7, The chemical industry reduces the impact on the environment during synthesis 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

To 3-amino-6-bromo-pyrazine-2-carboxylic acid (5.0g, 22.9mmol), HOBt (3.867g, 22.9mmol), EDCI (9.15g, 47.62mmol) and NEt3 (8mL, 58mmol) in DMF (80mL) was added C-((R)-1-Isopropyl-piperidin-3-yl)-methylamine (2.98g, 19.08mmol) in DMF (20mL). The reaction mixture was heated at 45oC for 18h before the volume reduced by half in vacuo and water was added. The aqueous phase was extracted with EtOAc and the combined organic phase was washed with sat. NaHCO3, brine, dried (MgSO4) and the solvent was removed in vacuo. The residue was purified by column chromatography (NEt3:THF 5:95) to give, after removal of the solvent in vacuo, the title compound: RT = 1.92 min; m/z (ES+) = 356.1, 358.1 [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, 3-Amino-6-bromopyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Hanrahan, Patrick; Bell, James; Bottomley, Gillian; Bradley, Stuart; Clarke, Phillip; Curtis, Eleanor; Davis, Susan; Dawson, Graham; Horswill, James; Keily, John; Moore, Gary; Rasamison, Chrystelle; Bloxham, Jason; Bioorganic and Medicinal Chemistry Letters; vol. 22; 6; (2012); p. 2271 – 2278;,
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. 767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, A new synthetic method of this compound is introduced below., COA of Formula: C16H13F6N5O

Example 2: (0128) Preparation of (R)-3-amino-l-(3-(trifluoromethyl)-5,6-dihvdro-ri,2,41triazolor4,3-alpyrazin- 7(8H)-yl)-4-(2A5-trifluorophenyl)butan-l-one (S)-3-(2-amino-2-oxoethyl)-5-methyl hexanoate (Sitagliptin diastereomeric salt). (0129) Mixture of (Z)-3-amino-l-(3-(trifluoromethyl)-5,6-dihydro-[l,2,4]triazolo[4,3-a]pyrazin- 7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-l-one (100. Og) and Monochlorobenzene (750.0ml) was cooled to 0-5°C. Sodium borohydride (24.4g; 2.66eq) followed by formic acid (330.0ml; 35.5eq) was added to the reaction mass at 0-5°C and maintained the reaction mass until the completion of the reaction i.e, until the TLC complies at the same temperature. Water (1600.0ml) was added after TLC complies and raised the temperature of the reaction mass to 50-55°C. Separated the aqueous & organic layers and washed the aqueous layer with Monochlorobenzene (200ml). To the aqueous layer Methelenedichloride (300ml) was added and adjusted the pH of the reaction mass to 10-11 with 48percent caustic lye. Separated the aqueous & organic layers and extracted the aqueous layer with Methelenedichloride (MDC). Combined all the organic layers and washed with 20percent sodium chloride solution, followed by water. Distilled off the Organic layer and co-distilled with isopropyl alcohol (100.0ml). To the obtained racemic Sitagliptin crude was added isopropyl alcohol (500.0ml) and (S)-3-(2- amino-2-oxoethyl)-5-methylhexanoicacid (28.0g), heated the mixture to reflux and slowly cooled to room temperature. Filtered the precipitated solid and washed with Isopropyl alcohol (100.0ml). To the wet cake isopropyl alcohol (200.0ml) was added and heated to reflux. Cooled the reaction mixture to room temperature filtered the product and washed with isopropyl alcohol (75.0ml). The wet cake was dried under vacuum at 50-55°C to obtain 57. Og of Sitagliptin diastereomeric salt. Molar yield: 38.7percent; Chiral HPLC: Desired product: 99.78percent; Isomer: 0.22percent, Purity by HPLC >99.0percent; SOR:-20.0°; Melting range: 168-172°C.

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; LEE PHARMA LIMITED; ALLA, Venkat Reddy; ALLA, Raghumitra; MALLEPALLI, Srinivas Reddy; NANDAM, Suresh Babu; GUDA, Madhukar Reddy; ALLURI, Raja Reddy; (33 pag.)WO2016/110750; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 20737-42-2, name is 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid, 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. name: 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid

Preparation of methyl (S)-3-(4-cyanophenyl)-2-((4-((3-((4-(3-hydroxypyrazine-2- carbonyl)piperazin-1-yl)methyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)propanoate (TA1026). HATU (1.2 equiv., 45 mg, 0.12 mmol) was added to a solution of 3- hydroxypyrazine-2-carboxylic acid (I-6, 1.1equiv., 15 mg, 0.11 mmol) in anhydrous DCM (1.5 mL) and DIPEA (3equiv., 0.040 mL, 0.23 mmol). After being stirred at r.t.10 minutes, TA1047 (1equiv., 46 mg, 0.098 mmol) was added. The resulting suspension was stirred at r.t. 1 h, followed by DMF (0.1 mL). Then the reaction was stirred for another 2 h until the LCMS analysis showed complete consumption of the starting material. The crude residue was then purified by reverse phase preparative HPLC (XBridge BEH, 19×150 mm, 5mum, C18 column; ACN/water with 0.1% formic acid modifier, 20mL/min), affording Compound TA1026 (15.1 mg, 25%) as a yellow solid.1H NMR (400 MHz, Methanol-d4) d 8.12 (d, J = 10.2 Hz, 1H), 7.71 – 7.65 (m, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.49 (s, 2H), 7.43 (d, J = 7.9 Hz, 3H), 7.34- 7.27 (m, 1H), 7.08 (dd, J = 17.7, 7.0 Hz, 1H), 4.96 (dd, J = 8.6, 5.8 Hz, 1H), 3.83- 3.77 (m, 2H), 3.71 (s, 2H), 3.60 (s, 2H), 3.43- 3.39 (m, 3H), 3.25- 3.14 (m, 3H), 2.58 (dt, J = 36.9, 4.7 Hz, 5H). MS (m/z): 595 [M+1]+, LCMS purity: 99%.

The synthetic route of 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ADURO BIOTECH, INC.; KATIBAH, George Edwin; KIM, Jung Yun; NDUBAKU, Chudi Obioma; ROBERTS, Tucker Curran; TJANDRA, Meiliana; (165 pag.)WO2019/245910; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5049-61-6, name is Pyrazin-2-amine, 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 5049-61-6, Safety of Pyrazin-2-amine

Step 1 ethyl imidazo[1,2-c]pyrazine-3-carboxylate Pyrazin-2-amine 4a (1 g, 10 mmol) was dissolved in 50 mL of ethylene glycol dimethyl ether, followed by addition of 50 mL of methanol and 3-bromo-2-oxo-propionate (2.30 g, 12 mmol). After stirring for 4 hours at room temperature, the reaction mixture was cooled to 0 C. and stirred for 30 minutes until a solid precipitated. The reaction mixture was filtered, and the filter cake was washed with ether (10 mL*3). The solid was dissolved in 50 mL of anhydrous ethanol and the solution was refluxed for 4 hours. The reaction mixture was concentrated under reduced pressure, added with 100 mL of dichloromethane, washed successively with saturated sodium carbonate solution (40 mL) and saturated sodium chloride solution (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain ethyl imidazo[1,2-a]pyrazine-3-carboxylate 14a (0.55 g, yield 28.9%) as a brown solid. MS m/z (ESI): 192.1 [M+1]

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, Pyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JIANGSU HANSOH PHARMACEUTICAL CO., LTD.; Tang, Peng Cho; Li, Xin; Li, Xiangqin; Chen, Yang; Wang, Bin; Zhu, Zhe; US2013/131068; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 723286-80-4,Some common heterocyclic compound, 723286-80-4, name is tert-Butyl 3-bromo-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate, molecular formula is C10H15BrN4O2, 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 0.173 g (0.571 mmol) OF 3-BROMO-7- (TERT-BUTOXYCARBONYL)- 5,6, 7,8-tetrahydro [1, 2, 4] triazolo [4, 3-a] pyrazine in 6 ML of methanol was added 0. 39 ML of 25% w/w solution of sodium methoxide in methanol. The reaction was heated at 65 C for 1 d. The reaction was diluted with ethyl acetate and washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate, and concentrated in vacuo. The crude product was purified by flash chromatography on a BIOTAGE system (silica gel, 5% methanol/ethyl acetate) to yield the title compound. LC/MS 255.1 (M+1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route tert-Butyl 3-bromo-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate, its application will become more common.

Reference:
Patent; MERCK & CO., INC.; WO2004/58266; (2004); 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 2,6-Dichloropyrazine

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXIII) (2 g,9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9 mmol). To this mixture wasadded 2,6-dichloropyrazine (LXIV) (1.428 g, 9.58 mmol) and the reaction was stirred at 95C for3 h. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layerwas dried over anhydrous Na2504, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes-*hexanes:EtOAc 1:1) to yield tert-butyl (1-(6- chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXV) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C,2H,7C1N402 mlz 285.1 (M+H).

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; HOOD, John; (240 pag.)WO2017/23975; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem