Pyrazines

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;,
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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

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

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;,
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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;,
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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;,
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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 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;,
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Pyrazine | C4H4N2 – PubChem

Electric Literature of 21279-64-1, 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. 21279-64-1 name is 5-Chloropyrazine-2-carboxamide, 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.

5-[18F]F-PZA was synthesized via a halogen exchange reaction, similar to the method used tosynthesize 5-F-PZA (Fig 2). 2960 MBq (80 mCi) of aqueous [18F]fluoride in ddH2O was purchasedfrom PETNET Solutions Inc. The [18F]fluoride was placed in a vial containing Kryptofix2.2.2 (5 mg, 13 mumol) and potassium carbonate (1 mg, 7 mumol) and the solution was thendried by azeotropic distillation. The solid residue was then re-solubilized with 0.2±0.3 mL ofacetonitrile containing 1±2 mg 5-chloropyrazinamide (5-Cl-PZA). The reaction mixture washeated in a securely capped 2 mL reaction vial at 105C for 8 min, and subsequently quenchedwith 0.8 mL water. The reaction mixture was filtered through a vented 0.22 um Millipore filterusing a 1 mL syringe and then purified by HPLC with an isocratic mobile phase of 8% acetonitrile/92% 0.02Maqueous ammonium acetate with 5% acetic acid (Phenomenex Luna PFP,250 × 10, 5 mum, 4 mL/min). The radioactive product eluted at the same retention time as the5-F-PZA standard (10 to 12 min). The solvent was removed by rotary evaporation. The residuewas re-solubilized in sterile phosphate buffered saline and the pH of the solution was adjustedto 7.4 by the addition of 2M NaOH. The solution was filtered through an Acrodisc 13 mmsyringe filter equipped with a 0.2 mum Supor membrane (Pall Corporation) into a sterile vial.Radiochemical purity was determined by reverse-phase analytical HPLC (Phenomenex PFP,250 × 4.6, 5 mum, 1 mL/min, 8% acetonitrile/92% 0.02Maqueous ammonium acetate with 5%acetic acid mobile phase).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloropyrazine-2-carboxamide, and friends who are interested can also refer to it.

Reference:
Article; Zhang, Zhuo; Ordonez, Alvaro A.; Smith-Jones, Peter; Wang, Hui; Gogarty, Kayla R.; Daryaee, Fereidoon; Bambarger, Lauren E.; Chang, Yong S.; Jain, Sanjay K.; Tonge, Peter J.; PLoS ONE; vol. 12; 2; (2017);,
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Synthetic Route of 98-97-5,Some common heterocyclic compound, 98-97-5, name is Pyrazine-2-carboxylic acid, molecular formula is C5H4N2O2, 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.

Pyrazinecarboxylic acid (2.72 g, 21.9 mmol) was added to a solution of L- cyclohexylglycine methyl ester (4.13 g, 19.9 mmol) in CH2CI2 (100 ml) at room temperature under N2, forming a white suspension. Triethylamine (6.33 ml, 4.62 g, 45.8 mmol) was added, followed by benzotriazol-l-yloxy-tris-(dimethylamino)- phosphonium hexafluorophosphate (BOP; 9.69 g, 21.9 mmol), which turned the reaction mixture from purple to an orange solution. After two days of stirring at room temperature the reaction mixture was washed two times with 50 ml saturated Na2CC>3, followed by the washing of the aqueous layers with CH2CI2 (2 chi 50 ml). The organic layers were collected and dried with MgSC , followed by concentration in vacuo. Purification by silica gel flash chromatography (c-Hex:EtOAc = 2: 1 with 0.5% triethylamine) afforded 9 (5.28 g, 19.03 mmol, 96%) as a yellow oil that solidified upon standing to give a white solid.[a f = +42.5 (c= 1.13, CHC13); *H NMR (250.13 MHz, CDCI3) delta = 9.39 (d, J= 1.25 Hz, 1H), 8.76 (d, J = 2.5 Hz, 1H), 8.57 (t, J = 1.5 Hz, 1H), 8.25 (d, J = 8.8 Hz, 1H), 4.74 (dd, J= 5.5, 9.3 Hz, 1H), 3.78 (s, 3H), 1.96 (m, 1H), 1.77 (m, 5H), 1.24 (m, 5H); 13C NMR (62.90 MHz, CDCI3): delta= 172.0 (C), 162.8 (C), 147.4 (CH), 144.5 (CH), 144.1 (C), 142.7(CH), 57.0 (CH), 52.3 (CH3), 41.2 (CH), 29.7 (CH2), 28.4 (CH2), 26.0 (CH2); IR (neat): v^cm ) = 3374 (m), 2920 (s), 2845 (w), 1740 (s), 1665 (s); HRMS (ESI, 4500 V): m/z calcd. for Ci4Hi9N303Na+ ([M + Na]+) 300.1319, found 300.1319.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Pyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; VERENIGING VOOR CHRISTELIJK HOGER ONDERWIJS, WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG; RUIJTER, Eelco; ORRU, Romano; ZNABET, Anass; POLAK, Marloes; TURNER, Nicholas; WO2011/103932; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem