Triazoles

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. 13423-60-4 name is 1-Phenyl-1H-1,2,4-triazole, 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. 13423-60-4

To 10 mL of chlorosulfonic acid at 0 C was added 1 g (6.9 mmol) of1-phenyl-1H-1,2,4-triazole, 35. The mixture was stirred overnight andthen cooled to 0 C. The solution was slowly added to ice and extracted3 three times with dichloromethane. The organic layers were combined,dried over sodium sulfate and concentrated to dryness in vacuo to give1 g of a tan solid. The crude sulfonyl chloride was used directlywithout further purification. To a microwave vial was added 25 mg(0.095 mmol) of the sulfonyl chloride, 15 mg (0.11 mmol) of 1,2,3,4-tetrahydroquinoline, 14 mg (0.014 mmol) of triethylamine and 300 muLof acetonitrile. The vial was sealed and heated at 130 C for 30 min. Themixture was diluted with dichloromethane and the organic phase waswashed 2 times with water and brine. The organic layer was dried oversodium sulfate and concentrated in vacuo. The crude sulfonamide waspurified by flash chromatography 0-75% EtOAc/Hexanes.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Phenyl-1H-1,2,4-triazole, and friends who are interested can also refer to it.

Reference:
Article; Okolotowicz, Karl J.; Dwyer, Mary; Ryan, Daniel; Cheng, Jiongjia; Cashman, Emily A.; Moore, Stephanie; Mercola, Mark; Cashman, John R.; Bioorganic and Medicinal Chemistry; vol. 26; 15; (2018); p. 4441 – 4451;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Adding some certain compound to certain chemical reactions, such as: 23579-79-5, name is 3,5-Dibromo-1-methyl-1H-1,2,4-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 23579-79-5. 23579-79-5

A mixture of 1,2,3,4-tetrahydroisoquinoline (1.1 g, 8.3 mmol), intermediate 32 (0.2 g, 8.3 mmol), K2CO3 (2.3 g, 16.6 mmol) in DMF (20 ml) was heated at 160 C. for 45 min using microwave irradiation. The r.m. was cooled and then poured onto H2O and extracted with DCM. The organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel (eluent: DCM/MeOH from 100/0 to 97/3). The product fractions were collected and concentrated in vacuo, yielding 900 mg of intermediate 33 (40%).

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 3,5-Dibromo-1-methyl-1H-1,2,4-triazole.

Reference:
Patent; Van Brandt, Sven Franciscus Anna; De Cleyn, Michel Anna Jozef; Gijsen, Henricus Jacobus Maria; Berthelot, Didier Jean-Claude; Surkyn, Michel; US2012/295891; (2012); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Adding some certain compound to certain chemical reactions, such as: 1001401-62-2, name is 2-(2H-1,2,3-Triazol-2-yl)benzoic acid, 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 1001401-62-2. 1001401-62-2

(S) – /ert-butyl 3-methyl-4-r5-methyl-2-(2H-1.2.3-triazol-2-v?benzoyll-1.4-diazepane-l- carboxylate (D-5)To a solution of 400 mg (1.87 mmol) D-4, 371 mg (1.96 mmol) B-3, 343 mg(2.24 mmol) 1-hydroxybenzotriazole hydrate, and 780 muL (5.6 mmol) triethylamine in 5 mL of DMF was added 537 mg (2.8 mmol) EDC and the reaction was stirred overnight at 500C. The reaction was partitioned between EtOAc and saturated aqueous NaetaCtheta3. The layers were separated and the organic was washed with water, brine, dried over MgSO4 and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel (EtOAc/hexanes) to provide D-5 as a colorless gum. Data for D-5: LC/MS: rt = 2.09 min; m/z (M + H) = 386.1, found; 386.2 required.

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 2-(2H-1,2,3-Triazol-2-yl)benzoic acid.

Reference:
Patent; MERCK & CO., INC.; WO2008/8518; (2008); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

135242-93-2, A common heterocyclic compound, 135242-93-2, name is (1-Methyl-1H-[1,2,4]triazol-3-yl)methanol, molecular formula is C4H7N3O, 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.

6-Cyclobutyl-3-(2-fluorophenyl)-4H-1,2,3-triazolo[1,5-alpha]pyrimidin-5-one (50 g, 0.18 mmol), triphenylphosphine (120 mg, 0.44 mmol) and (1-methyl-1H-1,2,4-triazol-3-yl)methanol (50 g, 0.44 mmol) were suspended in dry tetrahydrofuran (1.5 ml).. diethyl azodicarboxylate (70 mul, 0.44 mmol) was added and a solution resulted immediately.. The reaction was stirred at room temperature for 48 hours during which time a precipitate formed in the reaction mixture.. The crude reaction mixture was evaporated and recrystallized from EtOAc. The pale pink crystalline solid thus produced was collected by filtration and washed with diethyl ether to afford 6-cyclobutyl-3-(2-fluorophenyl)-5-(1-methyl-1H-1,2,4-triazol-3-ylmethoxy)-1,2,3-triazolo[1,5-alpha]pyrimidine (40 mg, 60%) as pale needles, m.p. 202-205 C.; deltaH (400 MHz, CDCl3) 1.84-1.92 (1H, m, CH(CH2)3), 2.06-2.16 (3H, m, CH(CH2)3), 3.67 (1H, quintet, J=9 Hz, CH(CH2)3), 3.94 (3H, s, NCH3), 7.19-7.29 (2H, m, ArH), 7.32-7.36 (1H, m, ArH), 8.04 (1H, s, triazole CH), 8.12 (1H, td, J=7.5 and 1.8 Hz, ArH), 8.55 (1H, d, J=1.5 Hz, pyrimidine CH); m/z (ES+) 380 (M+H+).

The synthetic route of 135242-93-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck Sharp & Dohme Ltd.; US6337331; (2002); B1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

13273-53-5, 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 13273-53-5 as follows.

Example 212 (5alpha,8alpha)-8-(5-Bromo-3-methyl-3H-[1,2,3]triazol-4-yl)-8-hydroxy-2-(4-isopropoxy-phenyl)-2-aza-spiro[4.5]decan-1-one A solution of 4-bromo-1-methyl-1H-1,2,3-triazole (108 mg) in tetrahyrofurane (5 mL) was cooled to -78 C. under an argon atmosphere and then treated dropwise with n-butyllitium (415 mul, 1.6 M in hexanes) over 10 minutes. The reaction mixture was stirred 15 min at -78 C., then treated dropwise with 2-(4-isopropoxyphenyl)-2-aza-spiro[4.5]decane-1,8-dione (200 mg in 3 ml tetrahydrofuran, product of example 184, step 2). The mixture was stirred further 1 h at -78 C. then warmed slowly to RT. It was then partitioned between AcOEt and saturated aqueous NH4Cl, the layers were separated, the organic layer washes with 1M aqueous HCL then brine and dried over Na2SO4. The solvent was evaporated off the residue purified by flash chromatography (silica gel, gradient of methylene chloride and AcOEt) to give the title compound (102 mg, 31%) as a white solid. MS (m/e): 465.131 [MH+].

According to the analysis of related databases, 13273-53-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ackermann, Jean; Brugger, Stephan; Conte, Aurelia; Hunziker, Daniel; Neidhart, Werner; Nettekoven, Matthias; Schulz-Gasch, Tanja; Wertheimer, Stanley; US2011/92512; (2011); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

288-36-8, 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. 288-36-8, name is 1H-1,2,3-Triazole, This compound has unique chemical properties. The synthetic route is as follows.

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 DCM with 0.1% AcOH) to give the faster eluting 2-(2H-l,2,3-triazol~2-yl)-5-methylbenzoic acid, followed by the undesired regioisomer isomer, I -(2H- 1 ,2,3-triazoI-2-yl)-5-methylbenzoic acid. A solution of the acid (3.56 g, 17.52 mmol) in 150 mL of DCM was stirred and cooled to O0C. The solution was treated with oxalyl chloride (1.9 mL, 21.9 mmol) and DMF (68 muL, .878 mmol). The solution was slowly warmed to room temperature and stirred overnight. Solvent was concentrated and the resulting solid was azetroped with DCM and concentrated to provide A-7 as a yellow solid.

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; MERCK SHARP & DOHME CORP.; BRESLIN, Michael, J.; COLEMAN, Paul, J.; COX, Christopher, D.; SCHREIER, John, D.; WHITMAN, David, B.; WO2010/48010; (2010); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Adding some certain compound to certain chemical reactions, such as: 7170-01-6, name is 3-Methyl-1H-1,2,4-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 7170-01-6. 7170-01-6

A mixture of compound precursor 5b (150 mg, 0.35 mmol), 3-methyl-1,2,4-triazole (581 mg, 7 mmol; 20 eq.; prepared by the method described in Coll. Czech. Chem. Comm. 1985, 49, 2492), copper powder (45 mg, 0.7 mmol; 2 eq.), potassium carbonate (97 mg, 0.7 mmol; 2 eq.) was flushed with anhydrous nitrogen and heated in a sealed tube at 160 C. for 11 h. Upon cooling, to the mixture was added MeOH, and the insoluble material was filtered. The filtrate was concentrated in vacuo and purified by C-18 reverse phase column (Prep. System eluting with MeOH-water containing 0.1% TFA) to obtain 19 mg (0.040 mmol, Y. 11%) of the title compound Example 216 as amorphous powder (TFA salt): MS m/e 474 (MH); 1H NMR (DMSO-d6) delta ppm 2.50 (3H, s, overlapped with DMSO peaks), 3.44 (4H, br, CH2N), 3.68 (4H, br, CH2N), 4.00 (3H, s, CH3O), 7.46 (5H, br. s, Ar-Hs), 7.89 (1H, s), 8.25 (1H, s), 9.24 (1H, s), 12.41 (1H, s, NH).

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 3-Methyl-1H-1,2,4-triazole.

Reference:
Patent; Wang, Tao; Zhang, Zhongxing; Meanwell, Nicholas A.; Kadow, John F.; Yin, Zhiwei; Xue, Qiufen May; Regueiro-Ren, Alicia; Matiskella, John D.; Ueda, Yasutsugu; US2004/110785; (2004); 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. 584-13-4, name is 4H-1,2,4-Triazol-4-amine, This compound has unique chemical properties. The synthetic route is as follows., 584-13-4

Example-2 4-Amino-1-[3,5-bis-(1-cyano-1-methylethyl)benzyl]-1H-[1,2,4]triazolium bromide (8) (Q. A.-Salt) Isopropanol (1.5 L), 3,5-bis-(1-cyano-1-methylethyl)benzylbromide (2) (100 g) and 4-amino-1,2,4-triazole (22.5 g) were charged in a flask at room temperature. The reaction mass was heated at 80-85 C. for next 5 hours. The reaction mass was further cooled down to room temperature and stirred for next one hour at 25-35 C. The precipitated solid QA-salt was filtered and washed with fresh isopropanol (100 mL*2). The Q.A.-salt was dried at 60-70 C. till LOD is less than 1.0%, giving solid product (74.4 g). m.p.: 198-200 C.

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; Solanki, Kirtipalsinh Saijansinh; Pal, Gautam; Haider, Hussain; Singh, Manoj Kumar; Kothari, Jay Shantilal; Agarwal, Virendra Kumar; US2009/221837; (2009); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole, I believe this compound will play a more active role in future production and life. 7170-01-6

Example 4 Synthesis of SC11 To a stirred solution of benzoic acid (116 mg, 0.94 mmol) in DCM (3 mL) were added compound 7 (200 mg, 0.94 mmol), TEA (0.4 mL, 2.82 mmol) and HBTU (536 mg, 1.39 mmol). The resulting mixture was stirred at r.t. overnight before quenched with sat. NaHCO3. The layers were separated and the aqueous layer was extracted with DCM (10 mL*3). The combined organic layers was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, 0?50% ethyl acetate in petroleum ether with 0.5% TEA) to provide compound 8 (164 mg, 55%) as a yellow solid. Compound 9 (303 mg, 100%) was obtained as a yellow oil by treating compound 8 (345 mg, 1.09 mmol) with 4N HCl/Dioxane (3 mL). To a solution of compound 12 (0.8 g; 4.5 mmol) in N-methylpyrrolidone (5 ml), water (0.5 ml) and hydrochloric acid (5-6 drops) were added. The mixture was stirred at 100 C. for 6 h. The mixture was cooled to room temperature and water (100 ml) was added. Then NaHCO3 sat. (20 ml) was added, the product was extracted with EtOAc (5*20 ml). Combined extracts were dried over Na2SO4 and concentrated to afford compound 13 (0.6 g, 81%) as pink solid. A solution of compound 13 (1.8 g; 11 mmol) in POCl3 (20 ml) was stirred at 100 C. for 12 h. Then POCl3 was evaporated under reduced pressure. To a residue ice water (100 ml) and then NaHCO3 sat. (25 ml) were added, the product was extracted with EtOAc (3*35 ml). Combined extracts were dried over Na2SO4 and concentrated to afford compound 14 (0.8 g, 40%) as light-yellow solid At 143 C., to molten 3-methyl-1H-1,2,4-triazole (744 mg, 8.95 mmol) under N2 atmosphere, was added compound 14 (392 mg, 1.79 mmol). After stirring for 20 hrs, the reaction mixture was cooled down to r.t. and partitioned between H2O (20 mL) and EA (20 mL). The layers were separated and the aqueous layer was extracted with EA (20 mL*3). The combined organic layers was dried over Na2SO4, filtered and concentrated. The residue was purified by prep. HPLC (C18, 10% to 89% acetonitrile in water (0.1% formic acid)) to compound 19 (182 mg, 44%) as a white solid. To a stirred solution of AlCl3 (1.588 g, 11.9 mmol) in DCM (10 mL) was added methyl 2-chloro-2-oxoacetate (389 mg, 3.18 mmol) and the resulting mixture was stirred at r.t. until it became a clear solution before introduction of compound 19 (182 mg, 0.79 mmol, in 1 mL DCM). The stirring was continued at r.t. overnight. After completion of the reaction, the mixture was quenched with sat. NaHCO3 and extracted with DCM (10 mL*3). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (silica gel, 0?90% ethyl acetate in petroleum ether) to provide compound 20 (58 mg, 23%) as a yellow oil. To a stirred solution of compound 20 (58 mg, 0.18 mmol) in MeOH/H2O (1 mL/2 mL) was added NaOH (15 mg, 0.37 mmol). After stirring at r.t. for 15 min, the reaction mixture was neutralized with 1N HCl, concentrated and lyophilized to provide compound 21 (73 mg, 95%, mixed with NaCl) as a green solid. Compound 21 (55 mg, 0.18 mmol) in DMF and compound 9 (59 mg, 0.27 mmol) were added to DIPEA (0.28 mL, 1.63 mmol) and DEPBT (325 mg, 1.09 mmol). After stirring at r.t. overnight, the reaction mixture was concentrated to remove DMF under the reduced pressure. The residue was partitioned between with EA (10 mL) and sat. NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with EA (10 mL*2). The combined organic layers was dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative HPLC to give compound SC11 (22 mg, 24%).

The chemical industry reduces the impact on the environment during synthesis 7170-01-6. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Drexel University; Cocklin, Simon; (79 pag.)US2016/214998; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole, molecular formula is C3H5N3, 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. 7170-01-6

To a vial charged with racemic 5-(benzofuran-2-yl)-3 – (5-bromo-6-methoxypyridin-2-yl)-5,6-dthydro-4H- 1 ,2,4-oxadiazine (110 mg, 0.28 mmol, 1.0 equiv.), 3-methyl-1H-1,2,4-triazole (47.1 mg, 0.57 mmol, 2.0 equiv.), and K3P04 (120 mg, 0.57 mmol, 2.0 equiv.) under N2 atmosphere was added degassed 4:1 PhMe:dioxane solvent mixture (2.00 mL). To a second vial charged with Pd2(dba)3 (20.8 mg, 0.02 mmol, 8.0 mol%) and Me4-di-t-BuXPhos (CAS 857356-94-6, 21.8 mg, 0.05 mmol, 16 mol%) under N2 atmosphere was added degassed 4:1 PhMe:dioxane solvent mixture (0.83 mL). This mixture was stirred for 3 minutes at 120 C to provide a dark red solution which was cooled to RT and transferred to the first vial. The reaction was degassed by bubbling with N2 for 5 minutes and then sealed. The reaction mixture was stirred at 120 C for 16 h. The reaction was cooled to RT and filtered through a pad of celite which was washed thoroughly with EtOAc. The filtrate was concentrated, and the residue was purified by normal phase chromatography on silica (0-5% MeOH / DCM) to afford 5-(Benzofuran-2-yl)-3-(6-methoxy-5-(3-methyl-1H- 1,2,4-triazol-1-yl)pyridin-2-yl)-5,6-dthydro-4H-1,2,4-oxadiazine (77.4 mg, 70%) as an off- white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7170-01-6, its application will become more common.

Reference:
Patent; FORUM PHARMCEUTICALS INC.; ACHARYA, Raksha; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; COOK, Andrew, Simon; HARRISON, Bryce, Alden; MCRINER, Andrew, J.; (451 pag.)WO2016/201168; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics