Month: May 2021

Electric Literature of 288-88-0, These common heterocyclic compound, 288-88-0, name is 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.

Intermediate 1 3,5-Dibromo-lH-l,2,4-triazole lH-l,2,4-Triazole (3.9 g, 56 mmol) was mixed in water (50 mL) and DCM (15 mL) at 0C. A solution of dibromine (6.1 mL, 119 mmol) in DCM (15 mL) and a solution of sodium hydroxide (6.78 g, 169 mmol) in water (20 mL) were added dropwise simultaneously while keeping the reaction temperature below 20C. The mixture was stirred at ambient temperature over night. Hydrochloric acid (cone, 2.0 mL, 66 mmol) was added. The solid was isolated by filtration, washed with water and dried under vacuum to yield the title compound as a solid (8.3 g, 65%). MS (ESI ) m/z 224 [M-H]”.

Statistics shows that 1H-1,2,4-Triazole is playing an increasingly important role. we look forward to future research findings about 288-88-0.

Reference:
Patent; ACTURUM LIFE SCIENCE AB; BESIDSKI, Yevgeni; YNGVE, Ulrika; PAULSEN, Kim; LINDE, Christian; MALMBORG, Jonas; WO2014/195322; (2014); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 6523-49-5, name is 4-(1,2,4-Triazol-1-yl)aniline, 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 6523-49-5, HPLC of Formula: C8H8N4

3 (160 mg, 1.00 mmol), MeOH (30 mL), Tnt-i (also called Tnt-A, see above 900 mg,1.25 mmol), AcOH (Cat.), NaCNBH3 (1.5 eq), RI, 20 h. Work up and column purification afforded 700 mg of 4.

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; UNITHER VIROLOGY, LLC; RAMSTEDT, Urban; WARFIELD, Kelly Lyn; TRESTON, Anthony; (147 pag.)WO2016/73652; (2016); 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. 60166-43-0, name is 1,4-Dimethyl-1H-1,2,3-triazole, A new synthetic method of this compound is introduced below., Computed Properties of C4H7N3

(S)-3-Bromo-7-chloro-5-(phenyl(tetrahydro-2H-pyran-4-yl)methyl)-5H- pyrrolo[2,3-b:4,5-b’]dipyridine (300 mg, 0.657 mmol), l,4-dimethyl-lH-l,2,3-triazole (77 mg, 0.788 mmol), Me4NOAc (87 mg, 0.657 mmol), and PdCl2(PPh3)2 (32.3 mg, 0.046 mmol) were weighed into a vial, and 12 mL NMP was added, and the air was replaced with argon. The sealed reaction vial was heated at 100 C with stirring overnight. The next morning, LC/MS showed the mono-alky lated product as the major peak and a significant amount of the dialkylated product. It was cooled to room temperature and diluted with EtOAc and washed twice with brine. The organic layer was dried over MgS04, and concentrated to obtain a crude mixture. The crude material was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19 x 200 mm, 5-muiotaeta particles; Mobile Phase A: 5:95 ACN: water with 10-mM NEUOAc; Mobile Phase B: 95:5 ACN: water with 10-mM NH4OAc; Gradient: 20-60% B over 15 min, then a 5- min hold at 100% B; Flow: 20 mL/min. Fractions containing the title compound were combined and dried via centrifugal evaporation. Estimated purity by LC/MS analysis was 99%. An analytical LC/MS injection was used to determine the final purity. Conditions: Column: Waters BEH CI 8, 2.0 x 50 mm, 1.7-muiotaeta particles; Mobile Phase A: 5:95 ACN:water with 10 mM NH4OAc; Mobile Phase B: 95:5 ACN:water with 10 mM NH4OAc; Temperature: 50 C; Gradient: 0%B, 0-100% B over 3 min, then a 0.5-min hold at 100% B; Flow: 1 mL/min; Detection: UV at 220 nm; RT = 1.51 min, LC/MS (M+H) = 534.5. NMR (500MHz, DMSO-c e) delta 8.82 (d, J=8.1 Hz, 1H), 8.67 (s, 1H), 8.57 (br. s., 1H), 7.77 – 7.71 (m, 3H), 7.35 – 7.29 (m, 2H), 7.27 – 7.21 (m, 1H), 6.06 (br. s., 1H), 4.38 (s, 3H), 4.03 (s, 3H), 3.90 (s, 1H), 3.74 (d, J=10.6 Hz, 1H), 3.62 (br. s., 1H), 3.40 (s, 1H), 3.24 (t, J=11.2 Hz, 1H), 2.54 (s, 3H), 2.31 (s, 3H), 1.62 (br. s., 1H), 1.51 – 1.39 (m, 1H), 1.35 – 1.21 (m, 1H), 1.14 (d, J=12.5 Hz, 1H); LC/MS (M+H) = 534.3 [Column: Waters Aquity BEH CI 8 2.1 X 50 mm 1.7u; Mobile Phase A: water with 0.05% TFA; Mobile Phase B: ACN with 0.05% TFA; Temperature: 40 C; Gradient: 2- 98% B over 1.5 min; Flow: 0.8 mL/min].

The synthetic route of 60166-43-0 has been constantly updated, and we look forward to future research findings.

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

Some common heterocyclic compound, 16681-70-2, name is 1H-[1,2,3]Triazole-4-carboxylic acid, molecular formula is C3H3N3O2, 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. Recommanded Product: 1H-[1,2,3]Triazole-4-carboxylic acid

3H-l,2,3-triazole-5-carboxylic acid (3.0 mg, 27 muiotaetaomicron) was combined with HATU (10.1 mg, 27 muiotaetaomicron) in DMF (0.5 mL); DIPEA (4.7 mu, 27 muiotaetaomicron) was added and the mixture was stirred for 5 minutes. Compound 2 (12 mg, 27 muiotaetaomicron) was dissolved in DMF (0.5 mL) and DIPEA (13.9 mu^, 80 muiotaetaomicron) and combined with the activated acid solution. The mixture was stirred for 10 minutes, at which time LCMS indicated the mass of the desired compound. The solvent was removed under reduced pressure and the residue was purified by reverse phase chromatography to yield Compound b (8 mg) as a TFA salt. MS m/z [M+H]+ calc’d for C27H33CIFN5O4, 546.22; found 546.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 16681-70-2, its application will become more common.

Reference:
Patent; THERAVANCE BIOPHARMA R&D IP, LLC; FLEURY, Melissa; BEAUSOLIEL, Anne-Marie; HUGHES, Adam D.; LONG, Daniel D.; WILTON, Donna A.A.; WO2015/116786; (2015); 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. 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., Formula: C2HBr2N3

Example 121: Preparation of 4,5-dibromo-l-methyl-lH-[l,2,3″|triazole and 4,5-dibromo- 2-methyl-2H-[l .2.31triazole(A) (B) To a solution of 4,5-dibromo- IH-[1, 2,3]triazole (2.26 g, 10 mmol) (Example 120) and triethyl amine (1.5 ml, 10 mmol) in dichloromethane (50 ml), was added methyl iodide (625 mul, 10 mmol). The reaction mixture was stirred at room temperature for 24 hours. More triethyl amine (0.75 ml, 5 mmol) and more methyl iodide (312 mul, 5 mmol) were added and the mixture was stirred for 3 hours. The reaction mixture was quenched by addition of aqueous ammonium chloride (saturated) (15 ml). The phases were separated and the organic phase was dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: 10-30% ethyl acetate in hexane) to give 4,5-dibromo-2-methyl-2H-[l,2,3]triazole (isomer B) (625 mg, 26% yield) and 4,5-dibromo- 1 -methyl- IH-[1, 2,3]triazole (isomer A) (825 mg, 34% yield).Isomer A 1H-NMR (400 MHz, CDCl3): 4.09 (s, 3H, Me) ppm. Isomer B 1H-NMR (400 MHz, CDCl3): 4.18 (s, 3H, Me) 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 15294-81-2.

Reference:
Patent; SYNGENTA LIMITED; WO2007/96576; (2007); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 202931-88-2,Some common heterocyclic compound, 202931-88-2, name is 1-Methyl-1H-1,2,3-triazole-5-carbaldehyde, molecular formula is C4H5N3O, 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 solution of 1-methyl-1H-1 ,2,3-triazole-5-carbaldehyde (Preparation 33, 5 g, 45 mmol) and sodium hydroxide (8.59 g, 215 mmol) in water (120 ml) at 150C was added dropwise a solution of potassium permanganate (5.83 g, 36.9 mmol) in water (120 ml). The reaction was stirred at room temperature for 30 minutes and then heated to reflux for 1 hour. The reaction was filtered and the filtrate acidified to pH 3 with concentrated HCI before extracting with ethyl acetate (3 x 100 ml). The combined organic extracts were washed with saturated aqueous brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound.LCMS Rt = 1.72 minMS m/z 128 [MH]+1HNMR (Cf4-CD3OD): 4.31 (s, 3H), 8.14 (s, 1 H)

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-1,2,3-triazole-5-carbaldehyde, its application will become more common.

Reference:
Patent; PFIZER LIMITED; WO2008/135826; (2008); A2;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 7343-33-1, 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.

Example 1Preparation of 3-bromo-1-(4-isopropoxyphenyl)-1H-1,2,4-triazole 3-bromo-1H-1,2,4-triazole (1.75 g, 11.8 mmol), copper(I) iodide (0.370 g, 1.94 mmol), cesium carbonate (4.98 g, 15.3 mmol), and 1-iodo-4-isopropoxybenzene (2.04 g, 7.78 mmol) (Katsumatu, T., et al. Macromolecular Chemistry and Physics, 2009, 210 (22), 1891-1902) was placed in dimethylsulfoxide (50 mL) and degassed with nitrogen for 10 minutes. The solution was heated at 100¡ã C. for 20 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered through Celite?. The resulting filter cake was rinsed with additional ethyl acetate (100 mL). The filtrate was washed with water (2*50 mL). The combined aqueous washes were neutralized with hydrochloric acid (2 N) as measured by pH paper. The aqueous solution was extracted with ethyl acetate (2*30 mL) and the organic extracts were combined, and then dried over anhydrous magnesium sulfate. The organic solution was concentrated onto Celite? and purified by silica gel chromatography using 0-100percent ethyl acetate/hexanes as eluent. The relevant fractions were concentrated to obtain the title compound as a yellow oil (0.540 g, 23percent): 1H NMR (400 MHz, CDCl3) delta 8.31 (s, 1H), 7.51 (d, J=9.1 Hz, 2H), 6.98 (d, J=9.0 Hz, 2H), 4.59 (p, J=6.1 Hz, 1H), 1.36 (d, J=6.1 Hz, 6H); ESIMS m/z 283 ([M+H]+).

The chemical industry reduces the impact on the environment during synthesis 5-Bromo-1H-1,2,4-triazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; DOW AGROSCIENCES LLC; Fischer, Lindsey G.; Crouse, Gary D.; Sparks, Thomas C.; Goldsmith, Miriam E.; (77 pag.)US2016/24026; (2016); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 7411-23-6, 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. 7411-23-6, name is 3,5-Dibromo-1H-1,2,4-triazole, This compound has unique chemical properties. The synthetic route is as follows.

Intermediate 5 3,5-dibromo-l-(2-methylpropyl)-lH-l,2,4-triazole Sodium te/t-butoxide (699 mg, 7.27 mmol) was added to a solution of 3,5-dibromo-l/-/-l,2,4- triazole (1.5 g, 6.61 mmol) in DMF (10 mL). The mixture was stirred at rt for 10 minutes. 1- Bromo-2-methylpropane (0.8 mL, 7.27 mmol) was added and the mixture was heated at 50C for 4 h and let to rt. Water (100 mL) was added and the mixture was extracted with EtOAc (2 x 50 mL). The organic phase was washed with brine (50 mL) and dried over sodium sulfate and concentrated to give the title compound as a liquid (1.47 g, 79%). XH NMR (400 MHz, CDCI3): delta ppm 0.94 (d, 6 H), 2.21 – 2.32 (m, 1 H), 3.93 (d, 2 H).

The chemical industry reduces the impact on the environment during synthesis 3,5-Dibromo-1H-1,2,4-triazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ACTURUM LIFE SCIENCE AB; BESIDSKI, Yevgeni; YNGVE, Ulrika; PAULSEN, Kim; LINDE, Christian; MALMBORG, Jonas; WO2014/195322; (2014); 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. 288-88-0, name is 1H-1,2,4-Triazole, A new synthetic method of this compound is introduced below., Product Details of 288-88-0

First, 3.8 g of 1,2,4-triazole were dissolved in 8 ml of NMP at 2O0C. Then,2.2 g of NaOH and 22 ml of NMP were added in portions over 1 hour, maintaining the temperature at less than 350C. The solution was stirred for 2 hours at 20C, and 7.8 g of Na2SO4 were then added. After filtration of the solid, the resulting solution was transferred to a dropping funnel, and added over 75 minutes to a solution of 14 g of crude l,3-benzenediacetonitrile-5-(bromomethyl)-alpha,alpha,alpha’,alpha’ tetramethyl (having a purity of 81.8%, containing: 3,5-bis(2-cyanoisopropyl)toluene 4.0%, l,l-dibromo-3,5-bis(2- cyanoisopropyl)toluene 10.7%, and other impurities 3.5% ) in 20 ml of NMP, cooled to -3O0C. At the end of the addition, the suspension was stirred at -300C for 18 hours, and monitored via HPLC. When the concentration of starting material is less than 0.5 percent, an amount of acetic acid sufficient to give a pH of about 6.5 to about 7.0 is added (an HPLC analysis of the crude reaction mixture showed: residual starting material 0.4%, Anastrozole 68.9%, Isoanastrozole 5.5%, 3,5-bis (2-cyanoisopropyl)toluene 7.5%, 1,1-dibromomethyl- 3,5-bis(2-cyanoisopropyl)benzene, and 15.4%, and other impurities 2.3%.). The mixture is then allowed to warm slowly to 200C, filtered, and 37 ml of toluene, 75 ml of heptane, and 37 ml of water are added. The biphasic system is stirred vigorously for 30 minutes, and the organic layer is then separated. Water, toluene, and heptane in amounts of 25 ml, 25 ml, and 50 ml, respectively, are added to the aqueous phase, and the system is stirred for 30 minutes before the organic phase is separated. Then, 10 ml of toluene and 20 ml of heptane are added to the aqueous phase, and the system is stirred for 30 minutes before the organic phase is separated. Toluene and water, 99 ml and 400 ml, respectively, are added to the aqueous phase, and the resulting biphasic system is stirred for 1 hour. The organic layer is separated and washed 3 times with a mixture of MeOH and water (3 ml and 21 ml, respectively). The final organic phase is concentrated to 45 ml under reduced pressure at 400C, and 45 ml of heptane are added dropwise over 1 hour. The resulting suspension is cooled to 00C, stirred for 1 hour, and filtered. The crude solid is dissolved in toluene (40 ml) at 4O0C, and heptane (40 ml) is slowly added under stirring. The suspension is cooled to 00C, stirred for 1 hour, EPO and filtered. The solid is driejd at 55C under reduced pressure until constant weight is achieved, yielding 5.8 g of product with a purity as follows: Anastrozole 98.45%, Isoanastrozole 0.09%, 3,5-bis (2-cyanoisopropyl)toluene 0.06%, l-bromo-3,5-bis (2- cyanoisopropyl)toluene 0.11%, l,l-dibromo-3,5-bis(2-cyanoisopropyl)toluene 0.07%, other impurities 1.22% are by HPLC.

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; SICOR, INC.; WO2006/108155; (2006); A2;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthetic Route of 184177-83-1, These 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, 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.

2-[(l S2S)-l-Ethyl-2-benzyloxypropyl]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-l- piperozinyl] phenyl]-3H-l,2,4-triazol-3-one (1 kg) was added to the Flask along with Dimethylsulfoxide (8 lit) at room temperature and stirred for 15 min. Solution of Sodium hydroxide (0.15 kg) in Water (0.3 lit) was added at same temperature and maintained for 1 hr. ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4- difluorophenyl)-tetrahydrofuran-3-yl)methyl-4-methylbenzene sulfonate (1.2 kg) was added and maintained for 4-5 hrs. Water (10 lit) was added to the reaction mixture and stirred for 15 min. Ethyl acetate (7.5 lit) was added and stirred for 15 min. Aqueous layer and Ethyl acetate layer were separated and aqueous layer was extracted with Ethyl acetate (3 lit). Aqueous layer and Ethyl acetate layer were separated and total aqueous layer was washed with Water (5 lit) and stirred for 15 min. Aqueous layer and Ethyl acetate layer were separated and Ethyl acetate layer was washed with brine solution. Aqueous layer and Ethyl acetate layer were separated and Ethyl acetate layer was dried over Sodium sulfate and distilled under vacuum at below 50C. The resultant crude was treated with Isopropyl alcohol (10 lit) and heated to 75-80C, maintained for material dissolved and treated with activated Carbon (0.05 kg) and maintained for 1 hr. The material was filtered through the Hyflow bed and washed with Isopropyl alcohol (1 lit). The resultant mass was cooled to room temperature, maintained for 2 hrs, filtered the solid and washed with Isopropyl alcohol (1 lit). Yield: 1.3Kg; HPLC: 98.6%.

The synthetic route of 184177-83-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; METROCHEM API PVT LTD.; NANDEPU, Venkateswara Rao; BIJJULA, Venkata krishna Reddy; BATHINA, Satyanarayana; (44 pag.)WO2019/77627; (2019); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics