Category: Triazoles

Reference of 1455-77-2,Some common heterocyclic compound, 1455-77-2, name is 3,5-Diamino-1,2,4-triazole, molecular formula is C2H5N5, 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: A suspension of 3,5-diamino-1,2,4-triazole (0.1 g, 1 mmol) in absolute EtOH (10 mL) was added to a stirring solution of azo-coupled precursors, Ia-IVa, (2 mmol) in absolute EtOH (50 mL) during a period of 10 min at 60-70 °C. The mixture was heated in water bath for 15 h at 80 °C with stirring. The mixture was filtered whilst hot and the obtained solid was washed with hot ethanol (three time) and then with diethylether. The resulted product was dried in air.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,5-Diamino-1,2,4-triazole, its application will become more common.

Reference:
Article; Khanmohammadi, Hamid; Erfantalab, Malihe; Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; vol. 86; (2012); p. 39 – 43;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Reference of 184177-83-1, A common heterocyclic compound, 184177-83-1, name is 1-((2S,3S)-2-(Benzyloxy)pentan-3-yl)-4-(4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one, molecular formula is C30H35N5O3, 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.

In a dry 300 L reactor, 70 kg of tetrahydrofuran was added under vacuum. The mixture was stirred, and after nitrogen replacement, the temperature was lowered to -10 C, and then 0.6 kg of sodium hydride was added in portions under nitrogen protection, and after stirring for 0.5 h, Continue to control the temperature T ? -10 C to add 12 kg of POB/24 kg of tetrahydrofuran solution to the system, After the dropwise addition, the mixture was stirred for 1 hour. Add 10 kg of POA/20 kg of tetrahydrofuran solution to the system. The reaction was carried out at a temperature of -10 to 0 C, and the monitoring until the POA disappeared. The temperature was controlled by T ? -10 C, and 1 kg of methanol was added dropwise. After stirring for 0.5 h, the reaction was quenched by adding 1 kg of water. Temperature control T ? 40 C under reduced pressure to concentrate about 70 L of tetrahydrofuran, Add 200 kg of dichloromethane and wash with 50 kg * 3 tap water. Wash with 50 kg of saturated brine, and dry the organic phase with 10 kg of anhydrous sodium sulfate. Filtration, temperature control T ? 40 C, concentrated under reduced pressure to no fraction, 60 kg of ethyl acetate was added while hot, and the temperature was raised to 70 C for 1 h. Then, the temperature is lowered to 0 to 10 C at a rate of 10 C / h, and suction filtration is performed. The filter cake was rinsed with pre-cooled 5 kg of ethyl acetate and drained. Transfer to the drying room at 40 ~ 45 C under reduced pressure for 40h, Received 19.2 kg of POC.

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; Borui Bio-pharmaceutical Taixing Co., Ltd.; Yuan Jiandong; Fu Xinliang; Cong Qilei; Xing Xiaopei; (14 pag.)CN109796446; (2019); A;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Application of 49607-51-4,Some common heterocyclic compound, 49607-51-4, name is 1-Methyl-1H-1,2,4-triazol-3-amine, molecular formula is C3H6N4, 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: 5 ml of toluene were added to 100 mg (0.22 mmol) of 5-[4-chloro-3-(trifluoromethyl)phenoxy]-2-(methylsulphonyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one (Example 40A) and 57 mg (0.67 mmol) of 4-amino-1H-pyrazole, and the mixture was then re-concentrated under reduced pressure. A drop of DMSO was added to the residue, and the mixture was then stirred at 150° C. for 1 h. The mixture was then purified directly by preparative HPLC [column: Chromatorex C18 10 mum, 250×30 mm; flow rate: 50 ml/min; run time: 45 min; detection: 210 nm; injection after 3 min of run time; mobile phase A: acetonitrile, mobile phase B: water; gradient: 10percent A (5.00 min)?95percent A (35.00-40.00 min)?10percent A (40.50-45.00 min)]. This gave 30 mg (31percent of theory) of the title compound.The Exemplary compounds below were prepared analogously to Example 104 from the appropriate 2-methylsulphonyl-substituted pyrimidinones and the respective amine components:(20percent of theory; without addition of DMSO)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-1H-1,2,4-triazol-3-amine, its application will become more common.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; STRAUB, ALEXANDER; COLLIN, MARIE-PIERRE; KOCH, MICHAEL; MEYER-KIRCHRATH, JUTTA; SCHLEMMER, KARL-HEINZ; NISING, CARL FRIEDRICH; BIBER, NICOLE; ANLAUF, SONJA; GROMOV, ALEXEY; WITTWER, MATTHIAS BEAT; (392 pag.)TW2016/5831; (2016); A;,
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. 15294-81-2, name is 4,5-Dibromo-1H-1,2,3-triazole, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C2HBr2N3

Step 1 : A mixture of A-21.1 (2.00 g, 1 1 .0 mmol), A-21.2 (3.88 g, 17.1 mmol), Cul (0.13 g, 0.68 mmol), A-21.3 (0.15 mL, 1 .03 mmol) and K2C03 (2.36 g, 17.1 mmol) in dry DMF (10 mL) is heated to 120°C by microwave for 40 min. The mixture is poured into water and extracted with Et20. The aq. phase is acidified with HCI (4M aq. solution) and extracted with EA. The combined organic phases are dried and concentrated to give the crude product which is purified by flash column chromatography on silica gel (using a solvent gradient from 100percent EA to EA/MeOH = 9/1 ) to provide 3.6 g of A-21.4. APCI+/-: 365 [M+H]+; HPLC (Rt): 1.10 min (method (0304) N).

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 15294-81-2.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; RIETHER, Doris; FERRARA, Marco; HEINE, Niklas; LESSEL, Uta; NICHOLSON, Janet Rachel; PEKCEC, Anton; SCHEUERER, Stefan; (69 pag.)WO2017/178341; (2017); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Electric Literature of 31250-99-4, A common heterocyclic compound, 31250-99-4, name is 1-Trityl-1H-1,2,4-triazole, molecular formula is C21H17N3, 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.

a) A solution of 1-trityl-1,2,4-triazole (10.0 g, prepared as described in Example 1) and N,N,N’,N’-tetramethylethylenediamine (3.8 g) in dry tetrahydrofuran (250 ml) was cooled to -70 C. under nitrogen. n-Butyllithium (22.2 ml, 1.6M solution in hexane) was added dropwise, with stirring, at such a rate that the internal temperature was maintained below -60 C. The red solution was stirred at -70 C. for twenty-five minutes, then treated dropwise with diethyl 3-oxo-propane phosphonate (6.20 g, prepared by formic acid deacetalisation of the diethyl acetal, DE 2517448, and also described in, for example, Tetrahedron 1981, 37, 1377) whilst maintaining the temperature at that level. The mixture was stirred for two and a half hours at -70 C. then quenched, at that temperature, with saturated aqueous ammonium chloride solution. It was extracted with ethyl acetate and the organic phase washed with brine, dried over magnesium sulphate, and evaporated under reduced pressure to give crude diethyl 3-hydroxy-3(1-trityl-1,2,4-triazol-5-yl)propane phosphonate (10.81 g). Chromatography on silica, using dichloromethane-ethanol (19:1) as eluant, gave pure material, m.p. 154-155 C. NMR (CDCl3): delta1.3(6H,t), 1.9(2H,m), 1.7(2H,m), 3.1(1H,br), 4.0(4H,m), 4.1(1H,t), 7.1-7.3 (15H,m), 7.9(1H,s). M/S: M+ 505.

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; Zeneca Limited; US5393732; (1995); A;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Reference of 15988-11-1, 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. 15988-11-1, name is 4-Phenyl-1,2,4-triazolidine-3,5-dione belongs to triazoles compound, it is a common compound, a new synthetic route is introduced below.

General procedure: A mixture of malononitrile 1 (1 mmol), aldehyde 2(1 mmol), 4-phenylurazole 3 (1 mmol), and zeolite (0.05 g)was placed in a mortar. The reaction mixture was then heatedat 80 C for 60 min. After completion of the reaction as monitored by TLC analysis, the reaction mixture was cooled,and the solid was dissolved in acetone (15 mL), filtered and evaporated under vacuum to give the product, which was crystallized from ethanol to afford pure compound 4.

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, 4-Phenyl-1,2,4-triazolidine-3,5-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Nejat, Razieh; Mahjoub, Mohammad Amin; Hekmatian, Zahra; Javidi, Mohammad Amin; Babashah, Sadegh; Journal of the Iranian Chemical Society; vol. 15; 5; (2018); p. 1133 – 1143;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Application of 202931-88-2, These common heterocyclic compound, 202931-88-2, name is 1-Methyl-1H-1,2,3-triazole-5-carbaldehyde, 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.

Example 5a: (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1,2,3-triazol-5-yl)methanolA solution of n-butyliithium in hexanes (1.6 M, 0.71 mL, 1.1 mmol) was added dropwise to a stirring solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (490 nig, 1.1 mmol, Intermediate 4: step d) in tetrahydrofuran (11 mL) at -78 C. After 2 minutes, a solution of 1-methyl-1H-1,2,3-triazole-5-carbaldehyde (140 mg, 1.1 mmol, Intermediate 18) in tetrahydrofuran (1 mL) was added dropwise. After 5 minutes, the flask was placed into an ice-water bath. After 1 hour, water (10 mL) and ethyl acetate (60 mL) were added. The biphasic mixture was stirred for 10 minutes. Half-saturated aqueous sodium chloride solution (50 mL) was added and the layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica, gel (4 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica, gel column for flash column chromatography purification. Elution with 100% hexanes initially, grading to 100% ethyl acetate provided the title compound as a white foam which was impure. The foam was suspended in methanol (20 mL) and the suspension was sonicated for 5 minutes. The solids were collected by filtration and rinsed with methanol (5 mL). The collected solids were dried to provide the title compound as a white solid. 1H NMR (600 MHz, DMSO-d6) delta ppm 8.42 (d, J = 2.5 Hz, 1H), 8.21 (d, J = 1.8 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.75-7.71 (m, 2H), 7,72-7.67 (m, 2H), 7.37-7.32 (m, 3H), 6.55 (d, J = 5.2 Hz, 1H), 6.53-6.49 (m, 1 H), 6.22 (d, J = 5.2 Hz, 1H), 4.30 (s, 2H), 4.04 (s, 3H), 3.97 (s, 3H); MS (ESI): mass calcd. for C24H21ClN6O2; 460.1 ; m/z found, 461.1 [M+H]+.(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol was purified by chiral SFC (Chiralpak A, 5 mum, 250 x 20 mm, mobile phase: 55% CO2, 45% methanol) to provide two enantiomers. Each enantiomer was further purified by preparative liquid chromatography (stationary phase: irregular 1 5-40 mum, 30 g Merck, mobile phase: 95% dichloromethane, 5% methanol). The first eluting enantiomer off the chiral column was Example 5b: 1H NMR (400 MHz, CDCl3) delta ppm 8.17 (d, J = 2,3 Hz, 1H). 7.90 – 7.82 (m, 2H), 7.68 (d, J = 1.7 Hz, 1H), 7.60 – 7.53 (m, 3H), 7.41 (d, J = 1.5 Hz, 1H), 7.40 – 7.33 (m, 2H), 6.46 – 6.39 (m, I H), 6.14 (s, 1H), 4.33 (s, 2H), 4.10 (s, 3H), 3.99 (s, 3H), 2.92 (br s, 1H): MS (ESI): mass calcd. for C24H21ClN6O2, 460.1 ; m/z found, 460.9 [M+H]+and the second eluting enantiomer was Example 5c: 1H NMR (400 MHz, CDCl3) delta ppm 8.17 (d, J = 1.9 Hz, 1H), 7.90- 7.82 (m, 2H). 7.68 i d. J = 1.7 Hz, 1H), 7.60 – 7.52 (m, 3H), 7.41 (s, 1H), 7.40 – 7.33 (m, 2H). 6.46 – 6.40 (m, 1H), 6.14 (s, 1H), 4.33 is. 2H), 4.10 (s, 3H), 3.99 (s, 3H), 2.92 (br s, 1H); MS (ESI): mass calcd. for C24H21ClN6O2, 460.1 ; m/z found, 460.9 [M+H]+.

Statistics shows that 1-Methyl-1H-1,2,3-triazole-5-carbaldehyde is playing an increasingly important role. we look forward to future research findings about 202931-88-2.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, Kristi, A.; BARBAY, Kent; EDWARDS, James, P.; KREUTTER, Kevin, D.; KUMMER, David, A.; MAHAROOF, Umar; NISHIMURA, Rachel; URBANSKI, Maud; VENKATESAN, Hariharan; WANG, Aihua; WOLIN, Ronald, L.; WOODS, Craig, R.; FOURIE, Anne; XUE, Xiaohua; CUMMINGS, Maxwell, D.; WO2015/57206; (2015); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 23579-79-5, 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. 23579-79-5 name is 3,5-Dibromo-1-methyl-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.

Bis(triphenylphosphine)palladium (II) chloride (2.487 mg, 3.54 .mol) was added to astirred mixture of 3-(tributylstannyl)-7-(triisopropylsilyl)-[1,2,3]triazolo[1,5-a]pyridine(10, 100 mg, 0.18 mmol) and 3,5-dibromo-1-methyl-1H-1,2,4-triazole (42.7 mg, 0.18mmol) and lithium chloride (22.53 mg, 0.53 mmol) dissolved in DME (1 mL) anddegased and purged with argon. The resulting mixture was heated at 130 C for 35minutes in the microwave. The mixture was evaporated under reduce pressure and theresidue was purified by preparative HPLC using a Waters X-Bridge reverse-phasecolumn (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml /minute) and decreasingly polar mixtures of water (containing 0.2% ammoniumcarbonate) and acetonitrile as eluent. The fractions containing the desired compound wereevaporated to dryness to afford 3-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)-7-(triisopropylsilyl)-[1,2,3]triazolo[1,5-a]pyridine (42.4 mg, 55%) as a white solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dibromo-1-methyl-1H-1,2,4-triazole, and friends who are interested can also refer to it.

Reference:
Article; Germain, Herve; Harris, Craig S.; Lebraud, Honorine; Tetrahedron Letters; vol. 52; 48; (2011); p. 6376 – 6378;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 7343-33-1, name is 5-Bromo-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. Formula: C2H2BrN3

3-bromo-1H-1,2,4-triazole (9.6 g, 64.9 mmol), pyridine (10.5 mL, 129.8 mmol), copper (II) acetate (17.7 g, 97.3 mmol) and (3-fluorophenyl) boronic acid (11.4 g, 81.1 mmol) were mixed in DCM (200 mL) and the reaction was stined at room temperature for 3 days. The solid was filtered off and the filtrate was washed with water several times. The organic layer was dried, concentrated and purified on silica gel to afford 6.3 g of desired product JW-2c in 38percent yield. ?H NMR (400 MHz, CDC13) oe 8.45 (s, 1H), 7.54 – 7.47 (m, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.20 – 7.04 (m, 1H) ppm. ESI-MS m/z calc. 240.96509, found 242.27 (M+1)+; Retention time:0.75 minutes.

The synthetic route of 5-Bromo-1H-1,2,4-triazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; DAVIES, Robert, J.; CAO, Jingrong; COCKERILL, Meghan, Elise; COLLIER, Philip, Noel; DENINNO, Michael, Paul; DOYLE, Elisabeth; FRANTZ, James, Daniel; GAO, Huai; GOLDMAN, Brian, Anthony; GREY, Ronald, Lee; GRILLOT, Anne-laure; GU, Wenxin; HENDERSON, James, A.; IRARRAZAVAL, Raul Eduardo, Krauss; KOLPAK, Adrianne, Lynn; LIAO, Yusheng; MAGAVI, Sanjay Shivayogi; MALTAIS, Francois; MESSERSMITH, David; PIERCE, Albert, Charles; PEROLA, Emanuele; RYU, Elizabeth Jin-Sun; SYKEN, Joshua; WANG, Jian; (706 pag.)WO2016/197009; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Electric Literature of 60166-43-0,Some common heterocyclic compound, 60166-43-0, name is 1,4-Dimethyl-1H-1,2,3-triazole, molecular formula is C4H7N3, 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.

(R)-l-(7-Chloro-5-(phenyl(tetrahydro-2H-pyran-4-yl)methyl)-5H-pyrrolo[2,3- b:4,5-b’]dipyridin-3-yl)ethanone (30.0 mg, 0.071 mmol), l,4-dimethyl-lH-l,2,3-triazole (10.4 mg, 0.107 mmol), tetramethylammonium acetate (11.4 mg, 0.086 mmol), and PdCl2(PPh3)2 (5.0 mg, 7.1 muetaiotaomicron) were weighed into a 20 mL scintillation vial. DMF (2 mL) was added and the air replaced with nitrogen. The reaction mixture was stirred at 100 C ovemight. The reaction was cooled to room temperature, diluted with EtOAc, and washed twice with brine. The organic layer was dried over MgSC>4 and concentrated. The crude material was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19 x 200 mm, 5-mupiiota particles; Mobile Phase A: 5:95 methanol: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol: water with 10- mM ammonium acetate; Gradient: 50-90% B over 20 min, then a 5-min hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the product was 84%. LC/MS [M+H]+ = 481 NMR (500MHz, DMSO-de) delta 9.13 (s, 1H), 8.84 (d, J=8.1 Hz, 2H), 7.72 (d, J=8.1 Hz, 3H), 7.33 – 7.28 (m, 2H), 7.25 – 7.21 (m, 1H), 6.04 (br. s., 1H), 4.34 (s, 3H), 3.89 (d, J=10.3 Hz, 1H), 3.72 (d, J=9.2 Hz, 1H), 3.58 (br. s., 1H), 3.51 (s, 3H), 3.46 – 3.39 (m, 1H), 3.25 – 3.15 (m, 1H), 2.78 (s, 3H), 1.59 (br. s., 1H), 1.51 (d, J=8.8 Hz, 1H), 1.31 (d, J=10.3 Hz, 1H), 1.07 (d, J=14.3 Hz, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1,4-Dimethyl-1H-1,2,3-triazole, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NORRIS, Derek J.; VACCARO, Wayne; DEBENEDETTO, Mikkel V.; DEGNAN, Andrew P.; DELUCCA, George V.; DESKUS, Jeffrey A.; HAN, Wen-Ching; KUMI, Godwin Kwame; SCHMITZ, William D.; STARRETT, John E., JR.; HILL, Matthew D.; HUANG, Hong; (563 pag.)WO2016/183118; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics