Day: June 23, 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. 706819-66-1, name is 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone, A new synthetic method of this compound is introduced below., Safety of 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone

General procedure: A 40 mL vial was charged with 5e (640 mg, 1.61 mmol), 12 (546 mg, 1.77 mmol), anhydrous MeCN (15mL) and -325 mesh K2CO3 powder (266 mg, 1.93 mmol). The mixture was stirred at 20 C for 18 h, before being diluted with EtOAc (15 mL) and H2O (15 mL). The phases were separated and the aqueous phase was extracted with additional EtOAc (2 x 10mL). The combined extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica (heptane – EtOAc) to afford 520 mg (52%) of 15d and 410 mg (41%) of 16d.

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:
Article; Wright, Stephen W.; Arnold, Eric P.; Yang, Xiaojing; Tetrahedron Letters; vol. 59; 4; (2018); p. 402 – 405;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 84547-84-2, 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. 84547-84-2 name is 4-Bromo-1-methyl-1H-pyrazole-5-carboxylic acid, 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.

A mixture of 4-bromo- 1 -methyl – 1 //-pyrazole-5-carboxylic acid (4.80 g, 23.4 mmol, CAS 84547-84-2) in THF (40.00 mL) was added BH3/THF (93.60 mL, 1 M). The mixture was stirred at 80 C for 12 hours under N2 atmosphere. To the mixture was added EtOAc (200 mL). The mixture was washed with saturated NaHCO, (200 mL x 3). The organic layer was dried over anhydrous Na2S04, filtered and concentrated to give a residue. The residue was purified by column chromatography (petroleum ether : ethyl acetate = 100 : 0 to 100 : 10) to give (4-bromo-l -methyl- li-pyrazol-5-yl)methanol (4.10 g, 92% yield) as a white solid. 1HNMR (400 MHz, DMSO-6): d 7.26 (s, 1H), 4.62 (s, 2H), 3.86 (s, 3H).

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

Reference:
Patent; RELAY THERAPEUTICS, INC.; D.E. SHAW RESEARCH, LLC; TAYLOR, Alexander, M.; LESCARBEAU, Andre; KELLEY, Elizabeth, H.; SHORTSLEEVES, Kelley, C.; WALTERS, W., Patrick; MURCKO, Mark, Andrew; MCLEAN, Thomas, H.; GUNAYDIN, Hakan; GIORDANETTO, Fabrizio; THERRIEN, Eric; (607 pag.)WO2019/183367; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

138786-86-4, name is Methyl 4-nitro-1H-pyrazole-3-carboxylate, 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. Formula: C5H5N3O4

Preparative Example 7 4-nitro-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester 340 mg (1.99 mM) of 4-nitro-1H-pyrazole-3-carboxylic acid methyl ester was dissolved in 4 ml of N,N-dimethylformamide, to which 0.33 ml (2.19 mM) of iodomethane and 1.3 g (3.98 mM) of cesium carbonate were added dropwise, and the resulting mixture was stirred under a nitrogen atmosphere for 30 minutes. The solvent was distilled off under reduced pressure, and the resultant was extracted with ethyl acetate and brine. The organic solvent layer was dried over anhydrous sodium sulfate, filtered, and then distilled under reduced pressure. The resulting impure compound was purified by column chromatography (hexane:ethyl acetate=2:1), to obtain 195 mg (53%) of the title compound and 110 mg (30%) of the compound of Preparative Example 13. 1H NMR (300 MHz, CDCl3) delta 4.00 (s, 3H), 4.02 (s, 3H), 8.15 (s, 1H). Mass: 185 (M+) ; 340 mg (1.99 mM) of 4-nitro-1H-pyrazole-3-carboxylic acid methyl ester was dissolved in 4 ml of N,N-dimethylformamide, to which 0.33 ml (2.19 mM) of iodomethane and 1.3 g (3.98 mM) of cesium carbonate were added dropwise, and the resulting mixture was stirred under a nitrogen atmosphere for 30 minutes. The solvent was distilled off under reduced pressure, and the resultant was extracted with ethyl acetate and brine. The organic solvent layer was dried over anhydrous sodium sulfate, filtered, and then distilled under reduced pressure. The resulting impure compound was purified by column chromatography (hexane:ethyl acetate=2:1), to obtain 110 mg (30%) of the title compound and 195 mg (53%) of the compound of Preparative Example 7.1H NMR (300 MHz, CDCl3) delta 4.03 (s, 3H), 4.04 (s, 3H), 8.03 (s, 1H).

The synthetic route of 138786-86-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; US2010/63106; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 948570-75-0, name is 1-(2-Methoxyethyl)-4-nitro-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 948570-75-0, HPLC of Formula: C6H9N3O3

A par flask was charged with 1-(2-Methoxy-ethyl)-4-nitro-1H-pyrazole 16 (2.5 g, 14.60 mmol) in EtOH (250 mL) followed by addition of Pd-C (20% w/w, 0.50 g). The flask was evacuated under vacuum and then purged with hydrogen. The reaction was stirred under hydrogen atmosphere (1 atm) for 1 6h. After the completion of reaction, the solution was filtered through sintered funnel with a pad of celite, washed with methanol and concentrated under reduced pressure to afford precursor-06 (2.0 g, 97% yield) that was taken as such for the next step without any further purification. ?H NMR (400 MHz,CDC13): 6 7.03 (s, 1H), 6.89 (s, 1H), 4.19-4.17 (t, 2H), 3.78 (br s, 2H), 3.67-3.64 (t, 2H), 3.21 (s, 3H). MS: 142.11 (M+H).

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, 1-(2-Methoxyethyl)-4-nitro-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JUBILANT BIOSYS LIMITED; VENKATESHAPPA, Chandregowda; SIVANANDHAN, Dhanalakshmi; BAKTHAVATCHALAM, Rajagopal; KETHIRI, Raghava Reddy; VISWANADHAN, Vellarkad Narayana; GIRI, Sanjeev; WO2015/25197; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 1222174-92-6, name is Methyl 5-bromo-1-methyl-1H-pyrazole-3-carboxylate, molecular formula is C6H7BrN2O2, 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: 1222174-92-6

A solution of intermediate 2a (500 mg), 2-(trifluoromethyl)beneneboronic acid (650 mg), PEPPSI-Ipr (77 mg) and potassium carbonate (939 mg) in dioxane (10 mL) were heated to 120 C. for 18 h. The mixture was chilled, filtered and the volatiles were removed under reduced pressure. The residue was purified by chromatography (Interchim cartridge50SiHP/12 g, Cy/EtOAc) to yield the desired compound (55% yield). [0378] LC-MS (Method 2): m/z [M+H]+=285.2 (MW calc.=284.23); Rt=0.83 min

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1222174-92-6, its application will become more common.

Reference:
Patent; Gruenenthal GmbH; Nordhoff, Sonja; Wachten, Sebastian; Kless, Achim; Voss, Felix; Ritter, Stefanie; US2014/194452; (2014); 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. 1128-54-7, name is 3-Methyl-1-phenyl-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., Formula: C10H10N2

General procedure: A clean and oven dry sealed tube was charged with 1-phenylpyrazole (1equiv.), and styrene (2.5equiv.), to this added (Rh-Complex 0.5mol%) and Cu(OAc)2.H2O (1 equiv), of water (1mL) as a reaction medium. Thereafter, the reaction mixture was heated at 90-100C under sealed conditions for 12h. The gain in product formation was examined by periodic monitoring through TLC. Then the reaction mixture was cool to room temperature, added water (50mL) and EtOAc (75mL) and the organic layer was extracted thrice, and dried over the anhydrous Na2SO4. The crude product was obtained by evaporating the solvent under reduced pressure. Finally, the product was purified through column chromatography (EtOAc/hexane).

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 1128-54-7.

Reference:
Article; Satrawala, Naveen; Williams, Cody; Srivastava, Avinash K.; Sharma, Kamal N.; Smith, Gregory S.; Joshi, Raj K.; Catalysis Communications; vol. 129; (2019);,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 133228-21-4, name is N,N-Dimethyl-1H-pyrazole-1-sulfonamide, 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 133228-21-4, category: pyrazoles-derivatives

12. 3-Ethyl-pyrazole-l-sulphonic acid dimethylamideTo a solution of pyrazole-1-sulphonic acid dimethylamide (13. Ig, 74.9 mmol) in anhydrous tetrahydrofuran (100 ml) at -78 0C under a nitrogen atmosphere was added dropwise a solution of n-butyl lithium in hexanes (1.6M, 51 ml, 82.3 mmol). The reaction was stirred thus for 30 minutes then iodoethane (6.6 ml, 82.4 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature then stirred thus over the weekend. EPO Water was then added and the solution was extracted with ethyl acetate. The separated organic liquors were washed with brine, dried (MgSO4) and concentrated to furnish the title compound as a yellow/ brown oil (12.6g, 85%).

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, N,N-Dimethyl-1H-pyrazole-1-sulfonamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL; ASTRAZENECA AB; WO2006/136829; (2006); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1453-58-3, 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 1453-58-3 as follows.

Preparation of tert-butyl 3-(bromomethyl)-1H-pyrazole-1-carboxylate After 3-methyl-1-pyrazole (2.0 g, 24.3 mmol) was dissolved in acetonitrile (25 mL), tert-butyl dicarbonate (6.5 g, 29.8 mmol) and 4-dimethylaminopyridine (0.31 g, 2.49 mmol) were added thereto at 0° C., and the mixture was slowly warmed to room temperature and then stirred for 2 hours. Ethyl acetate (50 mL) was added to the reaction material, and the result was washed with a 1N aqueous hydrochloric acid solution (50 mL), a saturated aqueous sodium hydrogen carbonate solution (50 mL) and salted water (50 mL), dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (ethyl acetate/normal-hexane=1/4) to give tert-butyl 3-methyl-1H-pyrazole-1-carboxylate (4.13 g, 93percent). 1H-NMR (300 MHz, CDCl3) delta 1.64 (s, 9H), 2.34 (s, 3H), 6.17 (s, 1H), 7.96 (s, 1H).

According to the analysis of related databases, 1453-58-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; SON, Jong Chan; KIM, Bong Jin; KIM, Jae Hak; LEE, Ill Young; YUN, Chang Soo; LEE, Sang Ho; LEE, Chong Kgo; US2014/249162; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 64517-88-0, 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. 64517-88-0, name is 1,3-Dimethyl-1H-pyrazol-4-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Example 48 2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (250 mg, 0.8 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (187 mg, 1.68 mmol), cesium carbonate (783 mg, 2.4 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (9 mg, 0.04 mmol) and BINAP (50 mg, 0.08 mmol) were added. The mixture was stirred in a microwave at 140 C. for 40 min. It was evaporated and the residue dissolved in MeOH was filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. Ether was added to the residue and a tan precipitate crashed out. It was filtered off and dried under vacuum at 40 C. for 2 days to afford the desired product (55 mg, 18%) as a tan solid. LC-MS (ES) m/z=387.1, [M+H]+=389.1. 1H NMR (400 MHz, DMSO-d6) delta ppm 11.93 (br. s., 1H) 9.51 (br. s., 1H) 8.03 (s, 1H) 7.96 (s, 1H) 7.82 (s, 1H) 7.51-7.61 (m, 3H) 7.07-7.15 (m, 1H) 6.68 (s, 1H) 3.70 (d, J=4.29 Hz, 6H) 2.07 (s, 3H).

The synthetic route of 1,3-Dimethyl-1H-pyrazol-4-amine 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

Some common heterocyclic compound, 70951-85-8, name is 4-Bromo-1-(tert-butyl)-1H-pyrazole, molecular formula is C7H11BrN2, 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. Product Details of 70951-85-8

A mixture of 4-bromo-1-tert-butyl-1H-pyrazole (3.3 g, 16.3 mmol), bis(pinacolato)diboron (8.3 g, 32.6 mmol), PdCl2(dppf) (1.8 g, 2.4 mmol), and KOAc (3.2 g, 32.6 mmol) in 1,4-dioxane (60 mL) was heated at reflux for 15 hours. After the completion of the reaction, the mixture was filtered and the filter cake was washed with EtOAc (100 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography using heptane/ethyl acetate (10% to 50%) as eluting solvents to afford 1-tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole as white solid (1.0 g, 25%). MS (ESI) m/z: 251 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 70951-85-8, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; DO, Steven; HU, Huiyong; KOLESNIKOV, Aleksandr; TSUI, Vickie, H.; WANG, Xiaojing; WO2014/1377; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics