Category: 486460-21-3

Application of 486460-21-3,Some common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C6H7F3N4, 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 (R) -3- [N- (tert- butoxycarbony1) amino] -4- (2, 4, 5-trifluoro-phenyl) butanoic acid ( 0.333 g, lmmol) of Example 8 and 3- ( trif luoromethyl- 5, 6, 7, 8-tetrahydro-l, 2, 4-triazolo [4, 3a] pyrozine (0.192 g, 1 mmol) in DMF (12 ml) was added HOBT (0.162 g, 1.2mmol) and EDC (0.230 g. 1.2 mmol) at 0 0C. After being stirred at room temperature for 16 h, DMF was evaporated and the residue extracted with ethyl acetate (3 X 20 ml) . The organic extracts were washed with NaHSO4 aq, then NaHCO3, then brine, and then dried over Na2SO4. Concentration was followed by purification by flash chromatography to afford 0.375 g of the title compound (71.8%) . 1H NMR (300 MHz, CDCl3) 7.10-7.00 (m, IH), 7.00-6.90 (m, IH), 5.25-5.35 (br, IH), 5.10-5.00 (m, IH), 4.90 (s, IH), 4.30-3.90 (m, 5H), 3.00-2.90 (m, 2H), 2.80-2.60 (m, 2H), 1.35 (s, 9H)

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

Reference:
Patent; CHIRAL QUEST, INC.; WU, Shulin; YU, Bo; WANG, Yejing; DELICE, Alain; ZHU, Jingyang; WO2010/78440; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486460-21-3,Some common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C6H7F3N4, 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.

Bis (trichloromethyl) carbonate (BTC) (495 mg, 1.7 mmol) was dissolved in 10 ml of methylene chloride and cooled in an ice-salt bath to reduce the internal temperature to -5 C to 0 C. (1.013 g, 4.2 mmo 1) was added to a mixture of pyridine (725 mg, 9.2 mmol) and 1- (2,3-difluoro-6-nitrophenyl) piperazine at 0 C, Omin added, maintained at 0 C reaction lh, directly to the next reaction.To the above reaction solution was added 3- (trifluoromethyl) -5,6,7,8-tetrahydro- [1,2,4] triazolo [4,3-a] pyrazine (800 mg, And triethylamine (842 mg, 8.4 mmol). The temperature of the reaction system was raised to room temperature and stirred for 20 h. The reaction was quenched by the addition of 20 ml of saturated sodium bicarbonate solution and extracted with dichloromethane (20 ml of X2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (petroleum ether: ethyl acetate = 3: 2) Yellow solid, 1.254 g, 48.1% yield in three steps.

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

Reference:
Patent; Shanghai Institute Of Pharmaceutical Industry; China State Institute of Pharmaceutical Industry; Meng, Xiangguo; Cai, Zhengyan; Zhou, Weicheng; Jiang, Jingzhang; Zhu, Yijun; Ge, Yuanyuan; Yan, Pingping; (32 pag.)CN103172635; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 486460-21-3, 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 486460-21-3 as follows.

Anhydrous DMF and N-ethyl-N-isopropylpropan-2-amine (20.88 mg, 0.162 mmol)were added to a mixture of HATU (28.7 mg, 0.075 mmol), HOAT (10.3 mg, 0.075 mmol), 1-(6-chloro-3-cyanoquinolin-4-yl)piperidine-4-carboxylic acid (17 mg, 0.054 mmol) and 3-(trifluoromethyl)-5 ,6,7, 8-tetrahydro- [1 ,2,4jtriazolo[4,3 -aj pyrazine (12.3 mg, 0.054 mmol).The mixture was stirred at room temperature for 6 hours. The reaction mixture was pouredinto 10 ml NaHCO3 aqueous solution, and the resulting suspension was stirred for 1 hour.The mixure was filtered and the filter cake was washed with water, and dried to afford the title compound.MS: 490 (M + 1). Human CYP8B1 1C50 (nM) 23.2

According to the analysis of related databases, 486460-21-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; CUMMING, Jared, N.; DYKSTRA, Kevin, D.; HRUZA, Alan; LI, Derun; LIU, Hong; TANG, Haiqun; TAOKA, Brandon, M.; VERRAS, Andreas; WALSH, Shawn, P.; WU, Wen-Lian; (170 pag.)WO2018/34918; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 486460-21-3, 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. 486460-21-3 name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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.

To a solution of 2-bromo-N-[1-(1 H-indol-3-ylmethyl)pentyl]thiazole-5- carboxamide (0.30 g, 0.74 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]pyrazine (0.17 g, 0.88 mmol) in dioxane (10 ml_), Cs2C03 (0.73 g, 2.22 mmol) and RuPhos (0.07 g, 0.14 mmol) were added and the reaction mixture was purged with argon for 30 min. Pd2(dba)3 (0.07 g, 0.07 mmol) was added and the reaction mixture was heated in sealed tube at 1 10C for 6h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was diluted with H2O (100 ml_) and extracted with EtOAc (2 x 100 ml_). The organic layer was separated, washed with brine (100 ml_), dried over anhydrous Na2SC>4 and concentrated in vacuo. The crude residue obtained was purified by column chromatography (silica, 100-200 mesh, 0 to 2% MeOH in DCM) and by preparative HPLC to afford N-[1-(1 H- indol-3-ylmethyl)pentyl]-2-[3-(trifluoromethyl)-6,8-dihydro-5H-[1 ,2,4]triazolo[4,3- a]pyrazin-7-yl]thiazole-5-carboxamide (0.035 g, 9%) as an off-white solid. HPLC Purity: 99.1 % MS (ESI) m/e [M+H]+/Rt/%: 518.00/2.84/98.4% 1H NMR (400 MHz, DMSO-cfe) delta 0.80 (t, J = 6.6 Hz, 3H) 1.17 – 1.33 (m, 4H) 1.44 – 1.56 (m, 2H) 2.78-2.96 (m, 2H) 4.03 (t, J = 5.2 Hz, 2H) 4.08 – 4.14 (m, 1 H) 4.30 (t, J = 5.0 Hz, 2H) 4.95 (s, 2H) 6.94 (t, J = 7.4 Hz, 1 H) 6.99 – 7.1 1 (m, 2H) 7.30 (d, J = 8.0 Hz, 1 H) 7.56 (d, J = 7.8 Hz, 1 H) 7.88 (s, 1 H) 8.07 (d, J = 8.5 Hz, 1 H) 10.76 (s, 1 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; UCB BIOPHARMA SPRL; HALL, Adrian; PROVINS, Laurent; MACCOSS, Malcolm; (72 pag.)WO2018/138088; (2018); 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., Computed Properties of C6H7F3N4

To adegassed solution of isopropyl (R)-2-amino-2-(4-bromophenyl)-4,4- dimethylpentanoate (57 mg, 0.017 mmol), 3-(trifluoromethyl)-5,6,7, 8-tetrahydro- [1 ,2,4jtriazolo[4,3-aj pyrazine (57 mg, 0.030 mmol), S-Phos phenethylamine chloride precatalyst (12 mg, 0.015 mol) in 1,4-dioxane (2 mL) was addedpotassium t-butoxide (57 g, 0.51 mmol). The reaction was stirred at 100C for 15 mm. The reaction mixture was cooled to rt, treated with saturated aq. ammonium chloride solution and EtOAc. The organic phase was dried over Na2SO4, filtered, concentrated down, and the residue was directly used in the next step.

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

Reference:
Patent; GILEAD SCIENCES, INC.; CAI, Zhenhong R.; CHO, Aesop; BUENROSTRO, Ana Zurisadai Gonzalez; HAN, Xiaochun; JABRI, Salman Y.; MCFADDEN, Ryan; QI, Yingmei; VOIGT, Johannes; YANG, Hong; XU, Jie; XU, Lianhong; (545 pag.)WO2019/75291; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 486460-21-3, 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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 6ATo a solution of the acid (VII’) (300 mg, 0.90 mmol) and triazolopiperazine (VIII) (170 mg, 0.90 mmol) in CH2CI2 (10 mL) is added /V-hydroxybenzotriazole (150 mg, 1 .08 mmol), and 10 minutes later, EDC (260 mg, 1 .35 mmol). The mixture, under an inert atmosphere of N2, is magnetically stirred for 4 hours until completion, then a saturated solution of sodium bicarbonate (5 mL) is added and the mixture is extracted with dichloromethane.The combined organic phases are dried and evaporated under reduced pressure. The product is purified by flash chromatography, obtaining 406 mg (86% yield) of a crystalline white solid, compound (IX’).1 H NMR (300 MHz, d6-dmso, 100 C) delta 7.4-7.2 (m, 7H), 6.90 (bs, 1 H) 4.97 & 4.90 (AB system, J= 12.9 Hz, 2 x 1 H), 4.92 (s, 2H), 4.26-4.14 (m, 3H), 3.97 (t, J=5.5 Hz, 2H), 2.92 & 2.67 (2 x dd, J=14.1 , 4.9 Hz, 2 x 1 H), 2.83-2.72 (m, 2H).

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-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CHEMO IBERICA, S.A.; RASPARINI, Marcello; TUFARO, Roberto Rocco; MINELLI, Cosima; WO2012/150328; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]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 486460-21-3, Formula: C6H7F3N4

44.0 g (0.50 mol, 1.0 eq) of 3-oxopropionic acid was dissolved in 220 g of dichloromethane solution, and N,N-dimethylformamide 0.36 g (0.021 mol, 0.01 eq) was added, and the chloride was added dropwise. Sulfuric acid 62.5g (0.525mol, 1.05eq), dripped, heated to backThe reaction was carried out for 6 hours, and the reaction of the raw material in the GC was completed. The temperature was lowered to 20 C or lower, 75.9 g (0.75 mol, 1.5 eq) of triethylamine was added dropwise, the temperature was lowered to 0 to 5 C, and 3-(trifluoromethyl)-5 was added. 1,7,8-Tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride 114.3 g (0.50 mol, 1 eq), stirred at room temperature for 2 hours, added 60 mL of water, The layer was extracted with methylene chloride (60 g×2), and the organic layer was combined and evaporated to dryness to give a crude product, which was recrystallized from a mixture of acetone/heptane 1:3 to obtain 98.6 g of compound (III).The yield was 75.3%, and the HPLC purity was 98.6%.

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; Anhui Haikang Pharmaceutical Co., Ltd.; Zhang Xiaoshun; (9 pag.)CN108314688; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C6H7F3N4, 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. Safety of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

At room temperature, a 50 ml three-necked flask was charged with F (2.6 g) prepared by the oxidation reaction ,J (1.9 g), DMF (20 ml), HOBT (0.22 g), N, N-diisopropylethylamine (2.6 ml). After the reaction solution was reduced to -15-15 C, EDC (3.0 g) was added and stirring was continued at -10-5 C for 30 minutes to 120 minutes. After the reaction solution was warmed to room temperature, the reaction was continued for 1 to 5 hours. Then, 50ml of ethyl acetate and water were added, stirred well, and separated. The aqueous layer was extracted once with 30ml of ethyl acetate. The organic layers were combined, washed with 30ml of water and concentrated to obtain G4.41g as an off white solid with a molar yield of 84.2%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 486460-21-3, its application will become more common.

Reference:
Patent; Chengdu Qianxilai Pharmaceutical Technology Co., Ltd.; Chen Shaowu; Yang Renming; (14 pag.)CN105017099; (2017); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486460-21-3,Some common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C6H7F3N4, 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.

Dichloromethane (100 ml) and the keto acid compound (10.0 g, 43.07 mmol) prepared in Example 8 were added to a 250 ml three-necked flask, and dissolved by stirring. Oxalyl chloride (6.56 g, 51.68 mmol) was added dropwise at 10 to 15 C, and the dropwise addition was completed, and the mixture was heated to 30 to 35 C to stir the reaction. The reaction was completed, and concentrated under reduced pressure at 30 to 40 C to dryness to pale-yellow liquid (10.91 g, 43.64 mmol), methylene chloride (100 ml), triethylamine (5.79 g, 57.24 mmol) and the above yellow liquid (10.0 g, 52.04 mmol) was dissolved by stirring. The solution of the free base (13.0 g, 52.04 mmol) / dichloromethane (20 ml) of the compound of the formula a was added dropwise to 0 to 5 C, and the dropwise addition was completed. After the completion of the dropwise addition, the mixture was heated to 10 to 15 C to stir the reaction. The reaction was completed, water was added and stirred. Layering, taking the lower organic phase and discarding the upper aqueous phase. The organic phase was washed with a 5% aqueous solution of sodium chloride and concentrated to dryness to dryness to dryness to afford white solid (19.24 g, 47.36 mmol) as a ketoamide compound in a molar yield of 91%.

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

Reference:
Patent; Zhejiang Ruibo Pharmaceutical Co., Ltd.; Gao Zhaobo; Zhang Xianyi; He Zhi; Mei Yijiang; Zheng Hui; (9 pag.)CN109956865; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H7F3N4

To a solution of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[ 1 ,2,4] triazolo[4,3-a]pyrazine ( 1.90 g) in DMF ( 10 mL) was added 2C03 (2.35 g) and l -bromo-3-chloropropane (1.70 mL) at rt. The reaction mixture was heated at 80 C for 3 h, diluted with water and extracted with ethyl acetate. The combined organic phases were dried over anhydrous Na2S04 for lh, and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 30: 1 (v/v) DCM/MeOH) to give the title compound as transparent liquid (0.68 g, 30.00 %).

According to the analysis of related databases, 486460-21-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; ZHANG, Jiancun; ZHANG, Yingjun; ZHANG, Weihong; LIU, Bing; ZHANG, Jiquan; LIU, Jinlei; ZHANG, Lu; WO2013/71697; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem