Month: June 2021

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. 138907-68-3, name is Ethyl 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., Application In Synthesis of Ethyl 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate

Intermediate 9; 5-Amiotano-1-(4-fluorophenyl)-1 /-/-pyrazole-4-carboxyliotac acid; To a suspension of ethyl 5-amiotano-1-(4-fluorophenyl)-1 /-/-pyrazole-4-carboxylate (12 1g, 48 5mmol) in ethanol (250ml) was added a solution of lithium hydroxide (5 8g, 242mmol) in water (100ml) The mixture was stirred at reflux for 2 5 hours It was allowed to cool and concentrated to 50% of its volume before 5M hydrochloric acid (47ml) was added. After stirring for 15 minutes, the resulting white solid was filtered off and further 5M hydrochloric acid (3ml) was added to the filtrate and the resulting solid was filtered and the combined solids were washed with water and diethyl ether and then dried under vacuum to give the title compound (10.27g).1H NMR (400 MHz, DMSOd6) delta ppm 12.09 (br. s., 1 H) 7.67 (s, 1 H) 7.54 – 7.60 (m, 2H) 7.34 – 7.41 (m, 2H) 6.29 (br. s., 2H). LC-MS Retention Time 2.20mins, MH+ 222.

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; GLAXO GROUP LIMITED; WO2008/777; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 14521-80-3, 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. 14521-80-3, name is 3-Bromo-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 3-bromopyrazole (1.00 g, 6.8 mmol) in ethyl ether (20 mL) was treated with 37% formaldehyde (0.3 mL, 4.0 mmol). The obtained solution was set aside at room temperature overnight. The volatiles were evaporated under reduced pressure. Toluene (5 mL) was added, and the evaporation was repeated. The obtained oil was triturated with ethyl ether (3 mL) to crystallize. The crystals were separated by decantation and dried to give 3-bromo-l- (hydroxymethyl)pyrazole (371 mg, 37%). A suspension of the obtained product in chloroform (5 mL) was treated with thionyl chloride (0.5 mL) and heated at reflux for 1 h. The volatiles were removed under reduced pressure to provide crude 3-bromo-l-(chloromethyl)pyrazole. A suspension of the unsubstituted triazinone from Example 38 (100 mg, 0.41 mmol) in DMF (3 mL) was treated with 60% NaH (18 mg, 0.45 mmol) followed by 3-bromo-l- (chloromethyl)pyrazole (82 mg, 0.49 mmol). After stirring for 1 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was chromatographed (chloroform/ethyl acetate, 1 : 1). The obtained material was recrystallized from ethanol (5 mL) to give the desired product, 70 mg, MP: 180-1810C. 1H NMR (CDCl3) delta 2.03 (1 H, m), 2.19 (1 H, m), 2.35 (1 H, m), 2.53 (1 H, m), 3.70 (1 H, m), 3.91 (1 H, dt, J = 12.3 and 7.2 Hz), 5.61 (1 H, t, J = 6.0 Hz), 6.55 ( 1 H, d, J = 13.8 Hz), 6.60 (1 H, d, J = 13.5 Hz), 7.51 (1 H, s), 7.85 (1 H, s), 7.87 (1 H, s), and 8.77 (1 H, s).

The chemical industry reduces the impact on the environment during synthesis 3-Bromo-1H-pyrazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; CORTEX PHARMACEUTICALS, INC.; WO2008/85505; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1192-21-8, A common heterocyclic compound, 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine, molecular formula is C4H7N3, 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 2 2-({5-Chloro-2-[(1-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-N-methylbenzamide A mixture of 2-[(2,5-dichloro-4-pyridinyl)amino]-N-methylbenzamide (100 mg, 0.338 mmol), 5-amino-1-methyl-1H-pyrazole (65.6 mg, 0.675 mmol), Cs2CO3 (220 mg, 0.675 mmol), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 61.8 mg, 0.068 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 48.8 mg, 0.084 mmol) was heated at 150° C. in a microwave oven for 30 min. The reaction mixture was filtered, and the filtrate was concentrated, and the resulting crude product was purified by reverse phase HPLC and the product was treated with 2 N HCl to give 34 mg of product as an HCl salt (24percent). LCMS (ES) m/z=357.1 (M+H); 1H NMR (400 MHz, methanol-d4) delta ppm 8.01 (s, 1H), 7.76-7.74 (m, 1H), 7.62-7.61 (m, 2H), 7.55 (d, J=2 Hz, 1H), 7.42-7.39 (m, 1H), 6.52 (s, 1H), 6.33 (d, J=2 Hz, 1H), 3.76 (s, 3H), 2.91 (s, 3H).

The synthetic route of 1192-21-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ADAMS, Jerry Leroy; Faitg, Thomas H.; Johnson, Neil W.; Lin, Hong; US2010/113475; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 1572-10-7, 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 1572-10-7 as follows.

Step 1: 5-Methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7(4H)-one A mixture of 5-phenyl-1H-pyrazol-3-ylamine (501 mg, 3.15 mmol) and 3-oxobutanoic acid ethyl ester (0.433 mL, 3.39 mmol) in anhydrous toluene (2.9 mL) is heated at 120 C. in a sealed vial. After 2 hr, the reaction is cooled to room temperature. The precipitate is collected in a Buchner funnel and washed with hexanes to afford 5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7(4H)-one (577 mg, yield 81%). LCMS: (AA) M+1 226; 1H NMR (400 MHz, DMSO) delta 12.35 (s, 1H), 8.01-7.92 (m, 2H), 7.49-7.43 (m, 2H), 7.42-7.37 (m, 1H), 6.57 (s, 1H), 5.60 (s, 1H), 2.29 (s, 3H).

According to the analysis of related databases, 1572-10-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; Afroze, Roushan; Bharathan, Indu T.; Ciavarri, Jeffrey P.; Fleming, Paul E.; Gaulin, Jeffrey L.; Girard, Mario; Langston, Steven P.; Soucy, Francois; Wong, Tzu-Tshin; Ye, Yingchun; US2013/217682; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – 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. 121507-34-4, name is 5-Isopropoxy-1H-pyrazol-3-amine, This compound has unique chemical properties. The synthetic route is as follows., Formula: C6H11N3O

Intermediate 76-Chloro-N-(5-isopropoxy-lH-pyrazol-3-yl)-3-nitropyridin-2-amine; A mixture of 2,6-dichloro-3-nitropyridine (0.5 g) and 5-isopropoxy-lH-pyrazo 1-3 -amine (Intermediate 6, 0.35 g) in acetonitrile (10 mL) with triethylamine (2 mL) was stirred at room temperature for 24 hours, The resulting mixture was concentrated, and the resulting residue was separated by silica gel column (etaexane/Ethyl acetate) to afford 0.45 g desired product. MS (electrospray): 298 (M+l) for CHHI2CIN5O3.

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 121507-34-4.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2008/135785; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 83-10-3, name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, molecular formula is C12H12N2O3, 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. category: pyrazoles-derivatives

Step 5) N-(4-((7-(2-hydroxy-2-methylpropoxy)quinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide To a solution of 1-((4-(4-aminophenoxy)quinolin-7-yl)oxy)-2-methylpropan-2-ol (3.75 g, 11.6 mmol) in DCM (31 mL) was added 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (2.7 g, 11.8 mmol), HOAT (0.32 g, 2.32 mmol), EDCI (2.7 g, 13.9 mmol). The reaction mixture was refluxed for 3 hours, then cooled to 45 C. and continued to stir for 4 hours. Additional EDCI (0.4 eq., 0.90 g, 4.64 mmol) was added and the reaction was stirred overnight at 45 C. The mixture was cooled to room temperature and diluted with a mixture of EtOAc (30 mL) and water (30 mL). After stirring at room temperature for 2 hours, the mixture was filtered. The solid was stirred in 95% EtOH (15 mL) at -5 C. for 5 hours. The solid was collected through filtration, dried in vacuo at 50 C. overnight to give the title compound as a gray-white solid (3.04 g, 48.87%). MS (ESI, pos. ion) m/z: 539.2 [M+1]; 1H NMR (400 MHz, CDCl3): delta 1.40 (s, 6H), 2.80 (s, 3H), 3.36 (s, 3H), 3.97 (s, 2H), 6.45-6.46 (d, J=5.2 Hz, 1H), 7.11-7.13 (d, J=8.56 Hz, 2H), 7.36-7.39 (m, 3H), 7.47-7.49 (d, J=6.8 Hz, 1H), 7.54-7.58 (m, 2H), 7.74-7.76 (d, J=8.4 Hz, 2H), 8.25-8.27 (d, J=9.04 Hz, 1H), 8.56-8.57 (d, J=5.08 Hz, 1H). 13C NMR (100 MHz, DMSO-d6): delta 11.46, 26.63, 33.31, 48.62, 68.63, 76.24, 97.04, 108.13, 119.04, 120.75, 121.56, 122.81, 127.19, 128.91, 129.51, 133.02, 136.46, 148.93, 151.82, 153.75, 160.37, 161.18, 161.24, 163.05.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 83-10-3, its application will become more common.

Reference:
Patent; XI, Dr. Ning; US2012/219522; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – 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. 13808-64-5, name is 4-Bromo-3-methylpyrazole, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

10330] To a suspension of NaH 60% in oil (0.3 g; 7.45 mmol) in tetrahydrofuran (150 mE) there is added, at 100 C., 4-bromo-3-methyl-1H-pyrazole dissolved in 15 mE of tetrahydrofuran dropwise, over 15 minutes. Afier stirring for 40 minutes at ambient temperature, iodomethane (0.45 mE; 7.45 mmol) is added dropwise, and then the reaction mixture is stirred overnight. Afier adding water, the reaction mixture is evaporated and taken up in dichloromethane. The organic phase is separated off and dried over Mg504, filtered and concentrated to dryness. The residue is purified by chromatography over silica gel to yield a mixture of the title compounds (4-bromo-1 ,3-dimethyl-pyrazole and 4-bromo-1 ,5- dimethyl-pyrazole respectively in a ratio of 4:6).4-bromo-1 ,5-dimethyl-1H-pyrazole10331] ?H NMR (500 MHz, dmso-d6) oe ppm: 7.41 (s, 1H),3.76 (s, 3H), 2.22 (s, 3H)4-bromo-1 ,3-dimethyl-1H-pyrazole10332] ?H NMR (500 MHz, dmso-d6) oe ppm: 7.81 (s, 1H),3.74 (s, 3H), 2.09 (s, 3H)

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; LE TIRAN, Arnaud; LE DIGUARHER, Thierry; STARCK, Jerome-Benoit; HENLIN, Jean-Michel; GUILLOUZIC, Anne-Francoise; DE NANTEUIL, Guillaume; GENESTE, Olivier; FEJES, Imre; TATAI, Janos; NYERGES, Miklos; DAVIDSON, James Edward Paul; MURRAY, James Brooke; CHEN, I-Jen; DURAND, Didier; US2015/31673; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 288-13-1, name is 1H-Pyrazole, belongs to pyrazoles-derivatives 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 288-13-1, Recommanded Product: 288-13-1

0535] Preparation of 1-(o-tolyl)-1H-pyrazole [0536] Operating protocol A (82 C., 70 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 383 ?l of 2-iodotoluene (3 mmoles), 136 mg of pyrazole (2 mmoles) and 1.2 ml of acetonitrile. [0537] The degree of transformation and selectivity for 1-(o-tolyl)-1H-pyrazole were 100%. [0538] The residue obtained was purified by silica gel chromatography (eluent: hexane/dichloromethane, 100/0 to 0/100). [0539] 297 mg of a pale yellow oil was obtained, corresponding to a yield of 94% by weight. [0540] The compound obtained had the following formula: [CHEMMOL-00045]

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; Cellier, Pascal Philippe; Cristau, Henri-Jean; Spindler, Jean-Francis; Taillefer, Marc; US2003/236413; (2003); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

497832-99-2, name is 4-Bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazole, belongs to pyrazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Recommanded Product: 497832-99-2

A mixture of 286 tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)silane (1.0 g, 3.0 mmol), 288 4-bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazole (822 mg, 3.6 mmol), and Pd(dppf)Cl2 (110 mg, 0.15 mmol), in a mixture of 80 acetonitrile (12 mL) and a 1 M aqueous solution of 179 NaHCO3 (5.4 mL) was bubbled with N2 for 1 min and then heated in a microwave reactor to 130 C. for 15 min. After cooling to rt, a 1 M solution of 289 TBAF in 10 THF (3 mL, 3 mmol) was added and the mixture was stirred at rt for 5 h, then diluted with CH2Cl2 and washed with water, brine, dried (MgSO4) and evaporated. The residue was purified (FCC, SiO2, 10-60% EtOAc/heptanes) to provide the 281 title compound (445 mg, 61% yield) as an off-white solid. 1H NMR (300 MHz, CDCl3) delta 7.45 (d, J=1.00 Hz, 1H), 7.28 (d, J=1.00 Hz, 2H), 6.88 (d, J=8.56 Hz, 2H), 5.16 (br s, 1H), 3.99 (s, 3H). [M+H]=243.2.

The synthetic route of 497832-99-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dart NeuroScience, LLC; Bookser, Brett; Botrous, Iriny; Branstetter, Bryan; Dyck, Brian; Weinhouse, Michael; US2019/177327; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 70951-85-8, The chemical industry reduces the impact on the environment during synthesis 70951-85-8, name is 4-Bromo-1-(tert-butyl)-1H-pyrazole, I believe this compound will play a more active role in future production and life.

A mixture of 4-bromo-1-(1 ,1-dimethylethyl)-1 H-pyrazole (2.4g, 1 1.82mmol), 4.4.4′.4′.5.5.5′.5′-octamethyl-2,2′-bi-1 ,3,2-dioxaborolane (3.00g, 1 1.82mmol), potassium acetate (2.90g, 29.5mmol), tris(dibenzylideneacetone)dipalladium (0) (0.108g, 0.1 18mmol), 2-(dicyclohexylphosphino)-2′.4′,6′-triisopropylbiphenyl (0.225g, 0.473mmol) in 1 ,4-dioxane (30ml) was degassed with nitrogen. The reaction mixture was spilt into 2 microwave vials and heated at 1 10C in a microwave for 1 .5h. There was no starting material remaining so the reactions were filtered through a bond elut reservoir and the residue was washed with ethyl acetate. The filtrate was concentrated in vacuo to yield the crude product. This was dissolved in DCM and purified through silica (50g) eluting with 0-50% ethyl acetate in DCM gradient. Appropriate fractions were combined and concentrated in vacuo to yield the title compound as a beige solid (1.68g).LCMS (Method B): Rt = 1 .08min, MH+ = 250.8

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-Bromo-1-(tert-butyl)-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; ATKINSON, Francis Louis; BARKER, Michael David; DOUAULT, Clement; GARTON, Neil Stuart; LIDDLE, John; PATEL, Vipulkumar Kantibhai; PRESTON, Alexander George Steven; WILSON, David Matthew; WO2011/134971; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics