Category: 486460-21-3

486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, belongs to Pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. category: Pyrazines

Select the above embodiment 1The corresponding enamine key intermediate compound of formula II (3.4 mmol)Join the reaction flask, thenAdding the corresponding compound of formula III3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (3.4 mmol)a solution of dichloromethane (50 mL),Control temperature is added at about 0CHOBT (545 mg, 4.2 mmol),Stir for 10 minutes,Then add EDC (1.9g, 10.0mmol),After removing the ice bath,Under stirring, the mixture was slowly heated to room temperature and stirred for 14 hours.After the reaction is over,The reaction solution is concentrated to remove the solvent,Get the corresponding residue,After silica gel column chromatography,The pure fractions are combined and then concentrated to dryness under reduced pressure.This afforded 1.3 g of compound of formula IV-1 as an off-white solid.

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

Reference:
Patent; Zhejiang Xin Donggang Pharmaceutical Co., Ltd.; Cheng Die; Lin Yi; Yan Jianbo; Hong Huabin; (23 pag.)CN107540677; (2018); A;,
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., Quality Control of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

Example 5: Preparation of 7-((S)-3-hydroxy-4-(2,4,5-trifluorophenyl)butyryl)-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (formula 7) [Show Image] 35 g of compound of formula 6a and 28.3 g of compound of formula 8 were dissolved in 364 mL dichloromethane, forming clear solution, which was pre-cooled to 16 C before adding of 23.5 mL N,N’-diisopropylcarbodiimide. During gradual addition (15 min) of carbodiimide, the temperature was maintained between 20 C to 25 C applying external cooling. After the addition, the reaction mixture was stirred at 23 C for 3 h and then aged 3 h at 0 C, forming white suspension of precipitated N,N’-diisopropylurea. Suspension was filtered and the precipitate was washed with 2 x 50 mL dichloromethane. Clear, yellowish-brown filtrate was washed with 360 mL of diluted hydrochloric acid (obtained from 350 mL of water and 7.0 mL of 6 N HCl), 380 mL 0.5 % aqueous sodium bicarbonate, and 350 mL water. Organic phase was evaporated at 50 C and 2 mbar, obtaining 58.4 g of clear, pale-brownish amber-like product of compound of formula 7, which solidified on standing. 1H NMR (DMSO-d6): delta 2.45-2.48(m, 1H), 2.65-2.78 (m,3H), 3.53-3.55(m, 2H), 3.96-4.21 (m,3H), 4.85-5.05(m,2H), 7.35-7.40 (m, 2H).

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

Reference:
Patent; LEK Pharmaceuticals d.d.; EP2397141; (2011); 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, Product Details of 486460-21-3

In 100 mL of tetrahydrofuran,4.11 g (41 mmol) of triethylamine was added,6.60g (20mmol) of compound IV and4.81 g (25 mmol) of 3-trifluoromethyl-1,2,4-triazolo[4,3-a]pyrazine was refluxed for 1 hour.TLC monitors the progress of the reaction,After the reaction is completed,Concentrated under reduced pressure,Purified by column chromatography,That is, the product sitagliptin 7.90g (19.4mmol),The yield was 97%, HPLC purity = 99.88%.

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; Shenzhen The Second People Hospital; Yan Dewen; Tan Hui; Zuo Xin; (8 pag.)CN109761988; (2019); A;,
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, Safety of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

Diisopropylethylamine at 0 C(Trifluorobenzyl) -5,6,7,8-tetrahydro- [1, 3-methyl-5-oxazol- 2,4] triazolo [4,3-a] pyrazine hydrochloride (3.37 g, 14.8 mmol) in dichloromethane (80 mL).A solution of 1-hydroxybenzotriazole (2.40 g, 17.8 mmo 1)After stirring, continue stirring at 0 C for 10 minutes,Then 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (3.40 g, 17.8 mmol) was added portionwise.Stir overnight at room temperature.After the reaction,Washed with saturated aqueous sodium bicarbonate solution,Drying and passing through column chromatography (RhoEpsilon: EpsilonAlpha = 1: 1 to 100 Epsilon) gave a white solid 9 (7.2 g, 95.2% yield)

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; Biortus Biosciences Co.,Ltd; ZHANG, HAI JUN; ZHANG, SHUAI; BIAN, WANG DONG; (12 pag.)CN103483340; (2016); B;,
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, Product Details of 486460-21-3

3S-t-butoxycarbonylamino-4-(5-methyl-2-oxo-oxazolidin-3-yl)-butyric acid benzyl ester 120 mg (0.31 mmol) of obtained in PREPARATION 19 was dissolved in methanol, then 12 mg of palladium/carcol (Pd/C) was added thereto, followed by stirring under hydrogen atmosphere for 3 hours, 40 minutes. After completion of a reaction, the reaction solution was filtered by Cellite, then washed with methanol, followed by concentration. 9 mg (0.31 mmol) of amine was added immediately thereto, then the resulting solution was dissolved in dichloromethane. The reaction was cooled to 0C, then 50 mg (0.37 mmol) of HOBT was added there. After stirring for 10 minutes, 88 mg (0.47 mmol) of EDC was added to thereto. After removal of an icebath, the reaction solution was stirred for abour 17 hours, then the concentrated residue was purified by prep-TLC (10:1 CH Cl :MeOH) to give 88 mg of the title compound in a total yield of 60%.[560] 1K NMR (CDCl3) delta 5.6-5.9(1H, m), 4.9-5.1(2H, m), 4.6-4.8 (IH, m), 3.9-4.3 (5H, m), 3.6-3.8 (IH, m), 3.1-3.5 (3H, m), 2.5-2.9 (2H, m), 1.40(12H, m)[561] Mass (m/e) 477 (M+l)

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; LG LIFE SCIENCES, LTD.; WO2006/104356; (2006); A1;,
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., COA of Formula: C6H7F3N4

A mixture of (3S,4S)-i -(6-chloro-3-cyanoquinolin-4-yl)-3 -methoxypiperidine-4-carboxylic acid (65 mg, 0.187 mmol), 3-(trifluoromethyl)-5,6,7,8-tetrahydro- [1,2,4jtriazolo[4,3-ajpyrazine (40 mg, 0.206 mmol), HATU (142 mg, 0.375 mmol) and DIPEA (131 1iL, 0.749 mmol) in DMF (3 mL) was stirred at 16 C for 1.5 h. Water (20 mL)was added and the mixture was extracted with EtOAc (3 x 8 mL). The combined organic layers were dried with Na2504, filtered and concentrated. The residue was purified by prepHPLC then dried by lyophilization to 6-chloro-4- [(3S,48)-3 -methoxy-4- { [3 -(trifluoromethyl)5 ,6-dihydro [1 ,2,4jtriazolo [4,3-al pyrazin-7(8H)-ylj carbonyl } piperidin- 1 -ylj quinoline-3- carbonitrile (Human CYP8B 1 150 (nM) 22) and 6-chloro-4- [(3S,4R)-3-methoxy-4- { [3-(trifluoromethyl)-5 ,6-dihydro [1 ,2,4jtriazolo[4,3 -ajpyrazin-7(8B)-ylj carbonyl } piperidin- 1- yljquinoline-3-carbonitrile (Human CYP8B1 1C50 (nM) 441). MS: 556 (M + 1).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 486460-21-3.

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

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.

HATU (490 mg, 1.3 mmol) followed by DIPEA (450 pi, 2.6 mmol) was added to astirred solution of 3 -(6-chloro-3-cyanoquinolin-4-yl)-3-azabicyclo [4.1. Ojheptane-6-carboxylic acid (280 mg, 0.86 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro- [1,2,4jtriazolo[4,3-ajpyrazine hydrochloride (240 mg, 1.0 mmol) in DMF (4.3 mL) at room temperature. The resulting mixture was stirred at room temperature for 15 hours, then diluted with water and extracted with EtOAc (3x). The combined organic layers were washed withwater (2x) and brine, then dried with Na2SO4, filtered and concentrated. The residue was purified by MPLC (24 g Si02 0->100% [(3:1) EtOH:EtOAcj:hexanes) to provide racemic product. MS: 502 (M + 1).The racemic product was further resolved by SFC (Column Whelk O(S,S) (2 x 25 cm) 45% (2:1) iPOH:MeCN (0.1% NH4OH)/C02) to provide 6-chloro-4- ((1 S,6R)-6-(3-(trifluoromethyl)-5 ,6,7, 8-tetrahydro- [1 ,2,4jtriazolo[4,3 -aj pyrazine-7-carbonyl)-3-azabicyclo[4.1.Ojheptan-3-yl)quinoline-3-carbonitrile (peak 1, SFC tR = 4.38 mm) (HumanCYP8B1 1C50 (nM) 1288). MS: 502 (M + 1) and 6-chloro-4-((1R,68)-6-(3-(trifluoromethyl)-5,6,7, 8-tetrahydro- [1 ,2,4jtriazolo [4,3-al pyrazine-7-carbonyl)-3 -azabicyclo [4.1. Ojheptan-3 -yl)quinoline-3-carbonitrile (peak 2, SFC tR = 5.29 mm) (Human CYP8B1 1C50 (nM) 1926).MS: 502 (M

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; 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

Reference 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.

DIPEA (0.307 mL, 1.759 mmol) was added to a mixture of 3-(trifluoromethyl)-5,6,7,8- tetrahydro-[ 1 ,2,4jtriazolo[4,3-ajpyrazine (127 mg, 0.660 mmol), cis-1 -(6-chloro-3- cyanoquinolin-4-yl)-2-methylpiperidine-4-carboxylic acid (145 mg, 0.440 mmol), and HATU(334 mg, 0.879 mmol) in DMF (4 mL) and stirred at 18 C for 3 h. The reaction was quenchedwith water (30 mL) and extracted with EtOAc (30 mL x 4), the combined organic phases were washed with brine (30 mL), dried over Na2SO4, filtered. The filtrates were concentrated and purified by p-HPLC to give cis-6-chloro-4-(2-methyl-4-(3-(trifluoromethyl)-5 ,6,7, 8-tetrahydro- [1 ,2,4jtriazolo [4,3-ajpyrazine-7-carbonyl)piperidin- 1 -yl)quinoline-3 -carbonitrile. MS: 504 (M + 1). The product was resolved by SFC (Column: Chiralpak AD-3 Mobile phase: A: CO2 B: methanol (0.05% DEA) Gradient: from 5% to 40% of B SFC separation gave peak 1(70mg, 0.135 mmol) MS: 504 (M + 1); and peak 2 (R,R or S,S) MS: 504 (M +1)

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine has been constantly updated, and we look forward to future research findings.

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

These common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-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. HPLC of Formula: C6H7F3N4

VI (2.0g, 5.0mmol) and 3- (trifluoromethyl) -5,6,7,8-tetrahydro – [1,2,4] triazolo [4,3-a] pyrazine (of 0.912 g , 4.7mmol) Was dissolved in 20ml of anhydrous N, N- dimethylformamide was added HOBt (0.770g, 5.7mmol) and EDC ¡¤ HCl (1.092g, 5.7mmol), stirred at room temperature 20h. After the reaction was added 20ml of water and 20ml of ethyl acetate, there Phase was washed with water 3 times, washed three times with saturated aqueous sodium carbonate solution, the organic phase was dried over anhydrous sodium sulfate, suction filtered, and concentrated to give yellow Colored foamy solid 2.967g, crude yield> 100%, recrystallized from ethyl acetate, filtration and drying to give a yellow solid 1.827g, Recrystallization yield of 63.6%.

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine has been constantly updated, and we look forward to future research findings.

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

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