Category: Triazoles

A common compound: 7411-23-6, name is 3,5-Dibromo-1H-1,2,4-triazole, belongs to Triazoles compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 7411-23-6

In a 100 mL round bottomed flask, 3,5-dibromo-1H-1,2,4-triazole (lnt-1, 2.50 g, 11 mmol) was dissolved in DMF (32 mL) and the solution was cooled to 0-5 C (ice bath). Sodium hydride (55% dispersion in mineral oil, 577 mg, 13.2 mmol) was added in portions and the resulting mixture was stirred for 5 min at 0-5 C and for 15 min at room temperature. After that, ethyl methanesulfonate (2.74 g, 2.27 mL, 22 mmol) was added dropwise at room temperature. The resulting mixture was stirred for 1.5 h at 100 C, and 16 h at room temperature. After that, it was concentrated in vacuo, the residue was diluted with ethyl acetate (100 mL) and water (100 mL), the aqueous phase was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo, the residue was purified by column chromatography (silica gel, 70 g, eluting with ethyl acetate / n-heptane, gradient 0: 100 to 22:78 v/v) to yield the title compound as white solid (1.98 g, 70%). HPLC (method LCMS_fastgradient) tR = 0.88 min. 1H NMR (CDCl3, 300 MHz): delta 1.49 (t, J = 7.2 Hz, 3 H), 4.21 (q, J= 7.2 Hz, 2 H). MS (ES+) m/z 253.9, 255.9, 258.0 [M+H, 2 Br isotopes] .

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, 7411-23-6, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BARTELS, Bjoern; BERCHTOLD, Stefan; GALLEY, Guido; GOERGLER, Annick; JAKOB-ROETNE, Roland; KRUMMENACHER, Daniela; LIMBERG, Anja; NEIDHART, Werner; RATNI, Hasane; REUTLINGER, Michael; RODRIGUEZ SARMIENTO, Rosa Maria; SCHNIDER, Christian; (309 pag.)WO2018/87018; (2018); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

7343-33-1, Adding a certain compound to certain chemical reactions, such as: 7343-33-1, name is 5-Bromo-1H-1,2,4-triazole, belongs to Triazoles 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 7343-33-1.

EXAMPLE 6 fPROCEDURES)(1 S,4a/?,6aS,7/?,8/?, 1 Oa/?, 10b/?, 12a/?, 1 AR, 15R)- 15-[[(2/?)-2-amino-2,3- dimethylbutyl]oxy]-14-(3-bromo-4H-l,2,4-triazol-4-yl)-8-[(l/?)-l,2-dimethylpropyl]-1 ,6,6a,7,8,9, 10, 10a, 10b, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 10a-tetramethyl-4//- 1 ,4a-propano-2H- phenanthro[l,2-c]pyran-7-carboxylic acid (EXAMPLE 6A) and(1 S,4a/?,6aS,7/?,8/?, 1 Oa/?, 10b/?, 12a/?, 14/?, 15R)- 15-[[(2/?)-2-amino-2,3- dimethylbutyl]oxy]-14-(5-bromo-/H-l,2,4-triazol-l-yl)-8-[(l/?)-l,2-dimethylpropyl]-1 ,6,6a,7,8,9, 10, 10a, 10b, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 1 Oa-tetramethyl-4//- 1 ,4a-propano-2H- phenanthro[l,2-c]pyran-7-carboxylic acid (EXAMPLE 6B) and( 1 S,4aR,6aS,7R,8R, 1 Oa/?, 1 Obi?, 12aK, 1 AR, 15R)- 15-[[(2i?)-2-amino-2,3- dimethylbutyl]oxy]-14-(3-bromo-7H-l,2,4-triazol-l-yl)-8-[(li?)-l,2-dimethylpropyl]- 1 ,6,6a,7,8,9, 10, 1 Oa, 1 Ob, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 1 Oa-tetramethyl-^H- 1 ,4a-propano-2H- phenanthro[l,2-c]pyran-7-carboxylic acid (EXAMPLE 6C)3-bromo-lH-l,2,4-triazole (32.1 mg, 0.217 mmol) and BF3OEt2 (54 mul, 0.426 mmol) were added to a stirred solution of Intermediate 6 (26.0 mg, 0.043 mmol) in 1,2- dichloroethane (0.43 ml). The reaction mixture was a light yellow solution that was heated to 5O0C. After 1.75 hr, LCMS and 1H NMR showed complete consumption of Intermediate 6. The reaction mixture was cooled to room temperature, the solvent was evaporated, and the resulting residue was placed under high vacuum. The residue was dissolved in methanol and separated using a single HPLC run on a 19 x 150 mm Sunfire Prep Cl 8 OBD 10 mum column by eluting with acetonitrile/water + 0.1percent TFA. The HPLC fractions containing the fastest eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6A (3.6 mg) as a white solid. The HPLC fractions containing the second eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6B (13.1 mg) as a white solid. The HPLC fractions containing the slowest eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6C (5.8 mg) as a white solid.EXAMPLE 6A: 1H NMR (CD3OD, 600 MHz, ppm) delta 0.76 (s, 3H, Me), 0.76 (d, 3H, Me), 0.81 (d,3H, Me), 0.84 (d, 3H, Me), 0.85 (d, 3H, Me), 0.88 (s, 3H, Me), 0.89 (d, 3H, Me), 0.94 (s, 3H, Me), 1.16 (s, 3H, Me), 1.20 (s, 3H, Me), 1.22-1.35 (m), 1.40-1.44 (m), 1.46-1.65 (m), 1.73-1.96 (m), 2.11-2.22 (m), 2.43 (broad dd, IH, H13), 2.79 (broad d, IH), 2.84 (s, IH, H7), 3.49 (d, IH), 3.53 (d, 2H), 3.60 (d, IH), 3.73 (broad d, IH), 3.94 (d, IH), 5.50 (dd, IH, H5), 5.72-5.80 (broad m, IH, H 14), 9.29 (broad s, IH, triazole).Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).EXAMPLE 6B:1H NMR (CD3OD, 600 MHz, ppm) delta 0.75 (s, 3H, Me), 0.76 (d, 3H, Me), 0.79 (d, 3H, Me), 0.83 (d, 3H, Me), 0.84 (d, 3H, Me), 0.88 (s, 3H, Me), 0.89 (d, 3H, Me), 0.91 (s, 3H, Me), 1.13 (s, 3H, Me), 1.19 (s, 3H, Me), 1.22-1.34 (m), 1.39-1.43 (m), 1.46-1.56 (m), 1.58-1.64 (m), 1.72-1.95 (m), 2.09-2.21 (m), 2.30 (dd, IH, H13), 2.83 (s, IH, H7), 2.85 (d, IH), 3.48 (d, IH), 3.48 (d, IH), 3.54 (dd, IH), 3.60 (d, IH), 3.88 (d, IH), 3.95 (d, IH), 5.47 (dd, IH, H5), 5.71-5.77 (m, IH, H14), 8.10 (s, IH, triazole). Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).EXAMPLE 6C:1H NMR (CD3OD, 600 MHz, ppm) delta 0.76 (s, 3H, Me), 0.77 (d, 3H, Me), 0.82 (d, 3H, Me), 0.85 (d, 3H, Me), 0.86 (s, 3H, Me), 0.86 (d, 3H, Me), 0.89 (d, 3H, Me), 0.92 (s, 3H, Me), 1.16 (s, 3H, Me), 1.20 (s, 3H, Me), 1.22-1.34 (m), 1.39-1.44 (m), 1.48-1.65 (m), 1.76-1.96 (m), 2.11-2.22 (m), 2.41 (dd, IH, H13), 2.72 (d, IH), 2.84 (s, IH, H7), 3.47 (d, IH), 3.50 (d, IH), 3.52 (dd, IH), 3.58 (d, IH), 3.72 (d, IH), 3.91 (d, IH), 5.48 (dd, IH, H5), 5.51-5.57 (m, IH, H 14), 8.52 (s, IH, triazole).Mass Spectrum: (ESI) m/z = 717.32 (719.32) (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, 5-Bromo-1H-1,2,4-triazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; GREENLEE, Mark, L.; WILKENING, Robert; APGAR, James; WILDONGER, Kenneth, James; MENG, Dongfang; PARKER, Dann, L.; WO2010/19203; (2010); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

288-36-8, Adding some certain compound to certain chemical reactions, such as: 288-36-8, name is 1H-1,2,3-Triazole, 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 288-36-8.

2-(2H-l,2,3-Triazol-2-vD-5-methylbenzoic acid (1-7)A solution of 2-iodo-5-methylbenzoic acid (4.0 g, 15.3 mmol) in DMF (10 mL) was treated with 1,2,3-triazole (2.1 g, 30.5 mmol), CsCO3 (9.95 g, 30.5 mmol), CuI (0.145 g, 0.76 mmol) and trans-N,N’-dimethylcyclohexane-l,2-diamine (0.43 g, 3.05 mmol). The mixture was heated at 120 0C for 10 min in a microwave reactor. The reaction was cooled to room temperature, diluted with water, and washed with EtOAc. The aqueous phase was acidified with IN HCl and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by gradient elution on SiO2 (0 to 10% MeOH in water with 0.1% AcOH) to give the faster eluting 2-(2H-l,2,3-triazol-2-yl)-5-methylbenzoic acid 1-5. followed by the undesired regioisomer isomer, l-(2H-l,2,3-triazol-2-yl)-5-methylbenzoic acid. Data for K7: 1HNMR (500 MHz, DMSO-d6) d 12.98 (br s , IH), 8.04 (s, 2H), 7.72-7.45 (m, 3H), 2.41 (s, 3H) ppm.

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 288-36-8.

Reference:
Patent; MERCK SHARP & DOHME CORP.; COX, Christopher, D.; FRALEY, Mark, E.; SCHREIER, John, D.; WO2010/48017; (2010); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

7170-01-6, These common heterocyclic compound, 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole, 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 50 mL dried two-neck flask were added 3-methyl-1H-1,2,4-triazole (650 mg, 7.8 mmol), 1-fluoro-4-nitrobenzene (1.0 g, 7.1 mmol) and potassium carbonate (2.0 g, 14 mmol), then DMF (10 mL) was added. The mixture was stirred at 80 C for 1 h under nitrogen protection. The mixture was cooled to rt and filtered. The filter cake was washed with DCM (20 mL), and the filtrate was concentrated in vacuo. To the residue was added water (20 mL). The mixture was stirred for 10 min and then a light yellow solid precipited out. The mixture was filtered by suction, and the filter cake was dried to give a light yellow solid (0.7 g, 48%). MS (ESI, pos.ion) m/z:205.1 (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 7170-01-6.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; WANG, Xiaojun; ZHOU, Pingjian; YANG, Chuanwen; HUANG, Changwei; XIONG, Shaohui; ZHANG, Yingjun; ZHANG, Jiancun; (139 pag.)EP3342765; (2018); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

6523-49-5, 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. 6523-49-5 name is 4-(1,2,4-Triazol-1-yl)aniline, 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.

A mixture of intermediate 21 (prepared according to A2. C-1) (0.00014 mol) and 4-(1H-1,2,4-triazol-1-yl)-benzenamine (0.00016 mol) in DMSO (0.5 ml) was reacted for 3 hours in a shaker at 100C, then the reaction mixture was shaken at 110C. Finally, the mixture was reacted in a microwave at 150C. The resulting precipitate was filtered off and dried (vacuum). Yield: 0.0096 g of final compound 51.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(1,2,4-Triazol-1-yl)aniline, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN PHARMACEUTICA N.V.; WO2005/12304; (2005); A2;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

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 252742-72-6 as follows. 252742-72-6

Example 53 (3R*,4R*)-N-[3,5-bis(trifluoromethyl)benzyl]-3-(4-fluorophenyl)-N-methyl-1-[(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]piperidine-4-carboxamide hydrochloride To a solution of the compound (0.30 g) obtained in Example 11 and potassium carbonate (0.083 mg) in 1percent H2O-DMF (5.0 mL) was added 5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (0.096 g) at 0¡ãC, and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the product was extracted with ethyl acetate. The organic layer was washed with brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC. The obtained product was treated with 1 equivalent of 4N hydrogen chloride/ethyl acetate solution to give the title compound as a white powder (0.30 g, 89percent). MS(ESI+): 560(M-HCl+H)

According to the analysis of related databases, 252742-72-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP1705176; (2006); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

A common heterocyclic compound, 6523-49-5, name is 4-(1,2,4-Triazol-1-yl)aniline, molecular formula is C8H8N4, 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. 6523-49-5.

A mixture of formamidine from Step 1 (400 mg) and 4-triazolyl-aniline (214 mg, 1 eq) in AcOH (3ml) was heated to 80 for 2 h. Cooled, and the resulting solid was isolated by filtration, washed with sodium bicarbonate, water and MeCN and dried to give pure title compound.1H NMR delta 10.27 (IH, br s), 9.29 (IH, s), 8.86 (IH, s), 8.63 (IH, s), 8.26 (IH, s), 8.22 (IH, dd, J 8.75 2.5Hz), 8.10 (2H, d, J 7.50Hz), 7.88 (4H, m), 7.72 (IH3 d, 7.5Hz), 7.34 (IH, t, 7.5Hz), 4.21 (2H, q, 7.5Hz), 1.41 (3H, t, 7.5Hz); LC-MS rt 2.53 m/z 427 ES+.

The synthetic route of 4-(1,2,4-Triazol-1-yl)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARROW THERAPEUTICS LIMITED; WO2007/80401; (2007); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

7170-01-6, name is 3-Methyl-1H-1,2,4-triazole, belongs to Triazoles compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 7170-01-6

[0005601 To a stirred solution of compound 1 (2 g, 1 eq) in DMF (40 mL), K2C03 (5.87 g, 3 eq) was added and stirred for 15 mm followed by the addition of compound 2 (1.17 g, 1 eq). The reaction mixture was stirred at 75 C for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with ice cold water and extracted with ethyl acetate (3 X 20 mL). Combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel 100-200 mesh using 50% EtOAchexane to afford the title compounds 3 and 3a. LCMS (mlz): 205.00 (M + 1).

Statistics shows that 7170-01-6 is playing an increasingly important role. we look forward to future research findings about 3-Methyl-1H-1,2,4-triazole.

Reference:
Patent; BIOMARIN PHARMACEUTICAL INC.; BHAGWAT, Shripad; WANG, Bing; LUEDTKE, Gregory R.; SPYVEE, Mark; (490 pag.)WO2016/57834; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

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. 7343-33-1, name is 5-Bromo-1H-1,2,4-triazole, This compound has unique chemical properties. The synthetic route is as follows., 7343-33-1

2- [6-Chloro-3- (ethanesulfonyl) pyridin-2-yl] -3-methyl-6- (trifluoromethyl)-3H-imidazo [4,5-b] 300mg, potassium carbonate 133 mg, and to a mixture of 3 mL of DMF, was added 3-bromo-1H-1,2,4-triazole 132mg under ice-cooling. After the mixture was stirred under ice-cooling for 2.5 hours, a saturated aqueous solution layer was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and saturated brine, and dried with anhydrous sodium sulfate. The resulting organic layer was dried under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 370mg of the compound of the present invention beta3 referred to below.

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; SUMITOMO CHEMICAL COMPANY LIMITED; NAKAJIMA, YUJI; OKAWARA, YUICHI; (263 pag.)JP2016/102104; (2016); A;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

288-88-0,Some common heterocyclic compound, 288-88-0, name is 1H-1,2,4-Triazole, molecular formula is C2H3N3, 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.

A mixture of 1,2,4-triazole (4.06 g, 58.7 mmol), potassium carbonate (9.05 g, 65.5 mmol), 4-fluorobenzaldehyde (6.3 ml, 58.7 mmol), and copper(I) oxide (0.26 g, 1.82 mmol) in pyridine (30 ml) is heated under nitrogen atmosphere at reflux overnight. After pyridine is distilled, the residue is diluted with chloroform, filtered, and washed with chloroform. The combined filtrate is washed with water, dried over magnesium sulfate, and concentrated in vacuo. The crude material is purified by column chromatography on silica with hexane/ethyl acetate (1:2) to give 4-(1,2,4-triazol-1-yl)-benzaldehyde and with ethyl acetate/methanol (19:1) to give 4-(1,3,4-triazol-1-yl)-benzaldehyde.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 288-88-0, its application will become more common.

Reference:
Patent; Japat Ltd.; US5703106; (1997); A;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics