Day: April 20, 2021

These common heterocyclic compound, 16681-70-2, name is 1H-[1,2,3]Triazole-4-carboxylic acid, 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. Safety of 1H-[1,2,3]Triazole-4-carboxylic acid

Example 15 (R)-5-(5?-Chloro-2?-fluorobiphenyl-4-O-2-hydroxymethyl-2-propyl-4-[(3H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid (isomers a and b) [0434] (R)-4-Amino-5-(5?-chloro-2?-fluorobiphenyl-4-yl)-2-hydroxymethyl-2-propylpentanoic acid (isomer a; 40 mg, 90 mumol, 1.0 eq.) and DIPEA (40 muL, 228 mumol, 2.5 eq.) were dissolved in DMF (200 muL). 1H-1,2,3-triazole-4-carboxylic acid (17 mg, 150 mumol, 1.5 eq.), HATU (45 mg, 120 mumol, 1.5 eq.), and DIPEA (40 muL, 228 mumol, 2.5 eq.) were dissolved in DMF (600 muL) and stirred at room temperature for a few minutes. The solutions were then combined and the resulting mixture stirred at room temperature until LC/MS analysis revealed consumption of starting material. The mixture was concentrated in vacuo and purified by preparative HPLC to yield the title compound (isomer a; 15.7 mg). LCMS (ESI): calc. C24H26ClFN4O4=488; obs. M+H=489.2. Retention time: 5.03 min. [0436] (R)-4-Amino-5-(5?-chloro-2?-fluorobiphenyl-4-yl)-2-hydroxymethyl-2-propylpentanoic acid (isomer b; 60 mg, 140 mumol, 1.0 eq.) and DIPEA (40 muL, 228 mumol, 1.6 eq.) were dissolved in DMF (300 muL). 1H-1,2,3-triazole-4-carboxylic acid (24 mg, 210 mumol, 1.5 eq.), HATU (57 mg, 150 mumol, 1.0 eq.), and DIPEA (80 muL, 456 mumol, 3.2 eq.) were dissolved in DMF (900 muL) and stirred at room temperature for a few minutes. The solutions were then combined and the resulting mixture stirred at room temperature and when the reaction was complete (as determined by LC/MS analysis), the mixture was concentrated in vacuo and purified by preparative HPLC to yield the title compound (isomer b; 33.7 mg). LCMS (ESI): calc. C24H26ClFN4O4=488; obs. M+H=489.2. Retention time: 4.98 min. [0437] LC/MS Method: flow rate: 1.5 mL/min; Buffer A: 0.1% TFA/H2O; Buffer B 0.1% TFA/MeCN; gradient elution from 5%-100% B over 9.6 minutes, then 100% B for 1.0 minute, detection at 254 nm.

The synthetic route of 1H-[1,2,3]Triazole-4-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THERAVANCE BIOPHARMA R&D IP, LLC; Fleury, Melissa; Beausoliel, Anne-Marie; Hughes, Adam D.; Long, Daniel D.; Wilton, Donna A.A.; US2015/209352; (2015); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

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. 16681-70-2, name is 1H-[1,2,3]Triazole-4-carboxylic acid, A new synthetic method of this compound is introduced below., HPLC of Formula: C3H3N3O2

Example 6 2-{(R)-3-(5?-Chloro-2?-fluorobiphenyl-4-O-2-[(1H-[1,2,3]triazole-4-carbonyl)amino]propyl}-2-methylmalonic Acid [0413] 1H-1,2,3-triazole-4-carboxylic acid (3.3 mg, 29 mumol) and HATU (10.5 mg, 28 mumol) were dissolved in DMF (2.0 mL) and stirred for 15 minutes at room temperature. 2-[(R)-2-Amino-3-(5?-chloro-2?-fluorobiphenyl-4-yl)propyl]-2-methylmalonic acid (12.0 mg, 32 mumol) and DIPEA (9.2 muL, 53 mumol) were added, and the resulting mixture was stirred for 15 minutes at room temperature, at which time LCMS indicated the mass of the desired compound. The mixture was concentrated in vacuo and the residue was purified by preparative HPLC to yield the title compound (5 mg) as a TFA salt. MS m/z [M+H]+ calc’d for C22H20ClFN4O5, 475.11. found 475.

The synthetic route of 16681-70-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THERAVANCE BIOPHARMA R&D IP, LLC; Fleury, Melissa; Beausoliel, Anne-Marie; Hughes, Adam D.; Long, Daniel D.; Wilton, Donna A.A.; US2015/209352; (2015); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 39602-93-2, name is 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, 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. COA of Formula: C3H7IN4

To a preweighed Erlenmeyer flask, 1.1726 grams, 5.18 mmoles of 1-methyl-4-amino-1,2,4-triazolium iodide was dissolved in twenty mL of fresh methanol and stirred vigorously with a Teflon stir bar. Silver nitrate, 0.8805 grams, 5.18 mmoles, was dissolved with 15 ml of methanol along with 3 ml of acetonitrile in a separate flask. The silver nitrate solution was added slowly to the vigorously stirred solution containing the 1-methyl-4-amino-1,2,4-triazolium iodide. After the addition of the silver nitrate solution was completed the reaction mixture was allowed to stir for 45 minutes more, then was filtered through a celite plug into a preweighed flask. The celite plug was washed with three five ml aliquots of fresh methanol. The filtrate flask was evacuated to leave a viscous oil which was then redissolved in 15 ml of fresh methanol and layered with 15 ml of diethyl ether, and subsequently placed in a refrigerator at 4¡ã C. After 24 hours the filtrate solution was decanted away from the precipitated viscous oil, which was washed with three 10 ml aliquots of fresh diethyl ether and vacuum dried to a constant weight, 0.7936 g, 4.92 mmoles of 1-methyl-4-amino-1,2,4-triazolium nitrate. Melting point 54-56¡ã C.; DSC onset 200¡ã C.1H NMR (d6-dmso): 4.051 (singlet); 6.991 (broad singlet); 9.079 (singlet); 10.116 (singlet).13C NMR (d6-dmso): 39.208 (singlet); 143.584 (singlet); 145.615 (singlet).

The synthetic route of 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Drake, Greg W.; Hawkins, Tommy; Tollison, Kerri; US7745635; (2010); B1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Application of 288-36-8,Some common heterocyclic compound, 288-36-8, name is 1H-1,2,3-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 2,3-dichloro-5-nitropyridine (50 g, 259.08 mmol), 1H-1,2,3-triazole (19.683 g, 284.99 mmol), potassium carbonate (46.549 g, 336.81 mmol) and CH3CN (200 mL) was heated to 40 C. and stirred overnight. Ethyl acetate (500 mL) was added. The mixture was washed with water (500 mL*2) and brine (500 mL), dried over anhydrous Na2SO4, filtered, and concentrated to dryness under reduced pressure. The residue was triturated with DCM (100 mL), filtered, and the solid was collected to afford compound 1i (40 g, 68%) as an off-white solid. LC-MS: (ES, m/z): [M+1]+ 225.9. 1H NMR (400 MHz, DMSO-d6) delta ppm 9.40 (d, J=2.0 Hz, 1H), 9.15 (d, J=2.0 Hz, 1H), 8.33 (s, 2H).

The synthetic route of 288-36-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Biotech, Inc.; Lu, Tianbao; Allison, Brett Douglas; Barbay, Joseph Kent; Connolly, Peter J.; Cummings, Maxwell David; Diels, Gaston; Edwards, James Patrick; Kreutter, Kevin D.; Philippar, Ulrike; Shen, Fang; Thuring, Johannes Wilhelmus John Fitzgerald; Wu, Tongfei; (412 pag.)US2018/170909; (2018); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Reference of 1001401-62-2, 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. 1001401-62-2, name is 2-(2H-1,2,3-Triazol-2-yl)benzoic acid belongs to triazoles compound, it is a common compound, a new synthetic route is introduced below.

Example 22 2-(2H-1,2,3-Triazol-2-yl)-N-(2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}cyclopentyl)benzamide Triethylamine (0.099 ml, 0.71 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (0.039 g, 0.29 mmol) and EDC (0.055 g, 0.29 mmol) were added to a solution 2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}cyclopentan-1-amine (Intermediate 12; 0.058 g, 0.24 mmol) and 2-(2H-1,2,3-triazol-2-yl)benzoic acid (CAS number 1001401-62-2; 0.054 g, 0.29 mmol) in DCM (3 ml). The reaction was stirred at room temperature for 24 hours and then diluted with DCM (40 ml) and washed with a saturated solution of sodium bicarbonate (10 ml). The organics were dried over magnesium sulfate, filtered through a hydrophobic frit and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-80% ethyl acetate/petrol) to afford the title compound. 1H NMR (400 MHz, DCM-d2) delta ppm 1.19-1.31 (m, 1H), 1.39-1.49 (m, 1H), 1.50-1.64 (m, 2H), 1.65-1.75 (m, 1H), 1.91-2.02 (m, 1H), 2.48-2.59 (m, 1H), 2.68-2.76 (m, 1H), 3.00-3.08 (m, 1H), 4.36-4.45 (m, 1H), 6.45-6.53 (m, 1H), 7.30-7.34 (m, 1H), 7.37 (s, 1H), 7.48-7.54 (m, 1H), 7.55-7.61 (m, 1H), 7.62-7.66 (m, 1H), 7.71-7.75 (m, 1H), 7.82 (s, 2H) and 8.59-8.62 (m, 1H). MS ES+: 416 Example 23 2-(2H-1,2,3-Triazol-2-yl)-N-(2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}cyclopentyl)benzamide Prepared according to the procedure for 2-(2H-1,2,3-triazol-2-yl)-N-(2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}cyclopentyl)benzamide (Example 22) except this was then was chirally separated using SFC (Waters prep30/MS system using 20% Ethanol, Daicel IA 10 mm id¡Á250 mm long columns at 30 ml min, 40 C. and 100 bar) to afford the title compound as a single enantiomer. 1H NMR (300 MHz, DCM-d2) delta ppm 1.15-1.35 (m, 1H), 1.35-1.79 (m, 4H), 1.85-2.06 (m, 1H), 2.42-2.63 (m, 1H), 2.64-2.79 (m, 1H), 2.95-3.16 (m, 1H), 4.28-4.53 (m, 1H), 6.44-6.59 (m, 1H), 7.26-7.43 (m, 2H), 7.43-7.68 (m, 3H), 7.69-7.77 (m, 1H), 7.82 (s, 2H), 8.54-8.68 (m, 1H). MS ES+: 416

The synthetic route of 2-(2H-1,2,3-Triazol-2-yl)benzoic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; Fieldhouse, Charlotte; Glen, Angela; Maine, Stephanie; Fujimoto, Tatsuhiko; Robinson, John Stephen; US2015/232460; (2015); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 31250-99-4, name is 1-Trityl-1H-1,2,4-triazole, molecular formula is C21H17N3, 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: C21H17N3

EXAMPLE 4 This Example illustrates the preparation of 1-trityl-5-iodo-1,2,4-triazole. A stirred solution of 1-trityl-1,2,4-triazole (9.95 g, prepared as described in Example 1) and N,N,N’,N’-tetramethylethylenediamine (3.71 g) in dry tetrahydrofuran (200 ml) was cooled to -70 C. under nitrogen and treated dropwise with n-butyllithium (22.0 ml, 1.6M solution in hexane). The solution was stirred for ten minutes, then treated rapidly with a solution of iodine (10.0 g) in dry tetrahydrofuran (40 ml). After a further one minute, the mixture was quenched at -50 C. with 0.1M sodium thiosulphate (100 ml) and portioned between dichloromethane and water. The organic layer was washed with water, dried over magnesium sulphate, evaporated under reduced pressure and the residue chromatographed on silica, using dichloromethane-ether (25:2) as eluant to give the title compound (11.73 g, m.p. 248-250 C.). NMR (CDCl3): delta7.1-7.3 (15H,m), 8.0(1H,s). 13 C NMR confirmed position of substitution. M/S: M+ 437

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 31250-99-4, its application will become more common.

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

Reference of 7170-01-6,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.

2- [6-Chloro-3- (ethanesulfonyl) pyridin-2-yl] -3-methyl-6- (trifluoromethyl)-3H-imidazo [4,5-b] pyridine 500 mg, 60% sodium hydride (oil) 60 mg, and the mixture DMF2.5mL, under ice-cooling 3-methyl-1H-1,2,4-triazole (synthesized by the method described in U.S. Patent application Publication 2006/0293304 Pat.) 113mg was added. 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 153mg of the compound of the present invention beta4 referred to below.

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

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

Synthetic Route of 288-36-8, A common heterocyclic compound, 288-36-8, name is 1H-1,2,3-Triazole, molecular formula is C2H3N3, 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.

Step 3: 4-(2H-1.2.3-Triazol-2-yl)thiophene-3-carboxylic acid (Intermediate F) To a mixture of the product from step 2 (7.9 g, 38 mmol), cesium carbonate (24.8 g,76 mmol) and Cul (2.88 g, 7.6 mmol) in DMF (200 mL) were added 2H-[l,2,3]triazole (5.24 g,76 mmol) and N,N’-dimethyl-cyclohexane-l,2-diamine (0.9 g, 6.5 mmol) and the mixture was heated to 110 C overnight. The cooled reaction mixture was adjusted to ~pH=12 with 1M sodium hydroxide aqueous solution and extracted with EtOAc (50 mL x 3). The aqueous layer was adjusted to ~pH=4 with 1M HC1 aqueous solution and extracted with EtOAc (50 mLx4). The extracts was dried over Na2SC>4, filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica (petroleum ether : EtOAc =10: 1) to provide the title compound. LRMS m/z (M+H) 196.0 found, 196.0 required.

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; MERCK SHARP & DOHME CORP.; KIM, Ronald; KUDUK, Scott, D.; LIVERTON, Nigel; ZHUO, Gang; (116 pag.)WO2016/100161; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 584-13-4, 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 584-13-4 as follows.

The ligand 4-(1H-imidazol-5-ylmethylene-amino)-4H-1,2,4-triazole (5-imztrz) (Fig. 1) was prepared by the condensation reaction of a modified literature procedure [21]. The dissolved 4-amino-1,2,4-triazole (1.68 g, 0.02 mol, 1.0 eq.) in ethanol was heated to boiling (80 C). Then, the second reactant 1H-imidazole-4-carbaldehyde (2.11 g, 0.022 mol, 1.1 eq.) dissolved in ethanol was added dropwise though a dropping funnel. After the complete addition few drops of catalytic H2SO4 were added. The reaction mixture was kept for refluxing for another 10 h. After cooling down to r.t., the excess of solvent was removed by rotary evaporator at 35 C. The obtained product was washed with small amounts of cold ethanol, diethyl ether and then dried in the desiccator with phosphorus pentoxide as dry agent. A light-yellow powder was obtained. Yield: 2.98 g (91.89%). m.p. 253.5-265.7 C. IR (KBr, cm1): 3109 (s),2838 (w), 1625 (vs), 1504 (vs), 1434 (s), 1386 (s), 1299 (s), 1214 (w),1175 (vs), 1060 (vs), 995 (s), 945 (w), 853 (s), 691 (m), 630 (vs), 510(m). 1H NMR (Fig. S1) (d6-DMSO): 9.07 (s, 2H, triazole), 8.92 (s, 1H,HACN), 7.91 (s, 1H, imidazole ring), 7.79 (s, 1H, imidazole ring).

According to the analysis of related databases, 584-13-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Li, Ai-Min; Rentschler, Eva; Polyhedron; vol. 154; (2018); p. 364 – 372;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 4923-01-7, name is 5-Methyl-4H-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. Formula: C3H6N4

General procedure: 3-Amino-1,2,4-triazole 8a-f (1.0 mmol), o-hydroxybenzaldehyde9a-e (1.0 mmol), acetone (10) (0.22 ml,3.0 mmol), and abs. EtOH (2 ml) were mixed in amicrowave process vial, and then 4 N solution of HCl indioxane (0.07 ml, 0.3 mmol) was added. The mixture wasirradiated at 150C for 30 min. The reaction mixture wascooled by an air flow and stirred for 24 h at roomtemperature for complete precipitation of the product. Theprecipitate was filtered off, washed with EtOH (1 ml) andEt2O (3¡Á1 ml), and dried. Compounds 1a-w were obtainedin a form of white solids.2,5-Dimethyl-11,12-dihydro-5,11-methano[1,2,4]triazolo[1,5-c][1,3,5]benzoxadiazocine (11a). Yield 48%,mp 310-311C. IR spectrum, nu, cm-1: 757, 1091, 1138,1325, 1485, 1548, 1625, 2885, 2922, 3070, 3421. 1H NMRspectrum, delta, ppm: 7.76 (1H, s, NH); 7.33-7.26 (1H, m,H Ar); 7.20-7.12 (1H, m, H Ar); 6.98-6.90 (1H, m, H Ar);6.82-6.76 (1H, m, H Ar); 4.52 (1H, s, 11-CH); 2.30 (2H, s,13-CH2); 2.02 (3H, s, 2-CH3); 1.91 (3H, s, 5-CH3).13C NMR spectrum, delta, ppm: 157.3 (C); 153.9 (C); 151.0(C); 130.0 (CH); 129.4 (CH); 124.4 (C); 121.2 (CH); 116.7(CH); 82.3 (C); 44.3 (CH); 32.3 (CH2); 24.0 (CH3); 14.2(CH3). Mass spectrum, m/z: 242 [M]+. Found, %: C 64.34;H 5.54; N 23.29. C13H14N4O. Calculated, %: C 64.45;H 5.82; N 23.12.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4923-01-7, its application will become more common.

Reference:
Article; Guemue?, Mustafa K.; Gorobets, Nikolay Yu.; Sedash, Yuriy V.; Chebanov, Valentin A.; Desenko, Sergey M.; Chemistry of Heterocyclic Compounds; vol. 53; 11; (2017); p. 1261 – 1267; Khim. Geterotsikl. Soedin.; vol. 53; 11; (2017); p. 1261 – 1267,7;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics