Month: June 2021

Synthetic Route of 136927-64-5, These common heterocyclic compound, 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, 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 the product of Example 4A in dioxane (1mL) were added 1- chloropyrrolo[1,2-a]pyrazine (64.3 mg, 0.421 mmol), palladium(II) acetate (7.89 mg, 0.035 mmol), xantphos (20.3 mg, 0.035 mmol), and potassium carbonate (146 mg, 1.05 mmol). The reaction mixture was heated at 80 C for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified with flash column chromatography (SiO2, heptane:ethyl acetate 0~100%) followed by preparative HPLC [Waters XBridge C185 mum OBD column, 30 × 100 mm, flow rate 40 mL/minute, 5-100% gradient of acetonitrile in buffer (0.1 % trifluoroacetic acid)] to give the title compound (8 mg, 0.020 mmol, 6% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 8.92 (s, 1H), 7.88 (d, J = 5.7 Hz, 1H), 7.86 – 7.82 (m, 1H), 7.52 (d, J = 4.3 Hz, 1H), 7.47 (t, J = 8.8 Hz, 1H), 7.05 (dd, J = 11.3, 2.9 Hz, 1H), 7.00 (d, J = 5.7 Hz, 1H), 6.87 – 6.81 (m, 2H), 4.51 (s, 2H), 2.57 (s, 6H); MS (ESI+) m/z 401 (M+H)+.

The synthetic route of 136927-64-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 109-08-0, name is 2-Methylpyrazine, 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 109-08-0, Application In Synthesis of 2-Methylpyrazine

100L enamel reaction kettle, equipped with material dropping pipe (connected with metering pump), equipped with chlorine gas introduction pipe (connected with chlorine gas automatic control system), automatic pressure control system, temperature detection chain control system. Add 96kg of solvent dichloroethane and 1kg of triethylamine to the reaction kettle and start stirring, then pass chlorine gas, and set the pressure in the kettle to be automatically controlled at 0.02-0.03MPa for 20-30 minutes. Then start feeding with a metering pump at a rate of 5kg/h (according to 10kg of methylpyrazine mixed with 10kg of dichloroethane to be used evenly), the reaction exotherm is obvious, the reaction temperature is controlled at 45 ~ 60 C , the temperature is higher than 60C. The feeding system is automatically cut off at (if necessary, the water flow can be manually controlled to lower the temperature), the beating is completed in about 4 hours, and then the reaction is continued for 30 minutes at a pressure of 0.02 ~ 0.03MPa. Then lower the temperature to 30-40C, introduce the residual chlorine gas in the reaction kettle into the lye spray absorption tower to absorb, the remaining reaction liquid in the kettle is pressed into the dichloroethane turnover tank with nitrogen through the pipeline filter (containing chlorine gas for recycling), the reaction kettle The remaining chloropyrazine hydrochloride solid is dissolved in 30Kg of water first, and then neutralized with 30% alkaline solution to pH 6-7, and then separated into layers to obtain crude chloropyrazine, about 12Kg, content about 92 % Is directly used for the next reaction.

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

Reference:
Patent; Shandong Jitian Biological Technology Co., Ltd.; Shandong Jitian Flavors Co., Ltd.; Yang Weixiang; Ren Wei; Yang Liang; Liu Shuzeng; Zhang Hongkui; Zhao Bin; Sun Yicheng; (6 pag.)CN110963974; (2020); A;,
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

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;,
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

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

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;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem