Day: July 16, 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. 176969-34-9, name is 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, A new synthetic method of this compound is introduced below., name: 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid

A solution of 293 g of 3-difluoromethyl-1-methylpyrazole-4-carboxylic acid, prepared analogously to example 2, in 700 g of toluene was heated at 90 C., and 260 g of thionyl chloride were added over a period of 3.5 h. The mixture was allowed to cool and concentrated under reduced pressure, 100 ml of toluene were added to the residue and the mixture was again concentrated under reduced pressure. The residue was distilled over a packed column at a pressure of 0.8 mbar and a head temperature of 109 C., which gave 298.4 g of the acid chloride of a purity of 99% (yield 92.1%).

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; BASF SE; US2010/69646; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 37687-24-4, 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. 37687-24-4, name is Diethyl 3,5-pyrazoledicarboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A mixture of diethyl 1H-pyrazole-3,5-dicarboxylate (3.00 g, 14.1 mmol), 2-bromo-1-[3-methyl-4-(trifluoromethyl)phenyl]ethanone (Intermediate 188A, 4.37 g, 15.5 mmol) and potassium carbo- nate (2.15 g, 15.5 mmol) in acetone (40 ml) was stirred at RT overnight. After filtering off the sol- ids, the filtrate was evaporated and the residue partitioned between dichloromethane and water. The organic phase was washed with water and brine, then dried over sodium sulfate and evapo- rated to give the title compound (5.70 g, 81 % of theory, 83% purity). LC/MS [Method 6]: Rt = 1.29 min; MS (ESIpos): m/z = 413 [M+H]+. 1H-NMR (400 MHz, DMSO-d6): d [ppm] = 8.11 (s, 1H), 8.04 (d, 1H), 7.90 (d, 1H), 7.36 (s, 1H), 6.30 (s, 2H), 4.31 (q, 2H), 4.20 (q, 2H), 2.55 (s, 3H), 1.31 (t, 3H), 1.19 (t, 3H). 19F-NMR (376 MHz, DMSO-d6): d [ppm] = -60.95 (s, 3F).

The synthetic route of Diethyl 3,5-pyrazoledicarboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER AKTIENGESELLSCHAFT; BAYER PHARMA AKTIENGESELLSCHAFT; MUeLLER, Steffen; SCHOHE-LOOP, Rudolf; ORTEGA, HERNANDEZ, Nuria; SUeSSMEIER, Frank; JIMENEZ NUNEZ, Eloisa; BRUMBY, Thomas; LINDNER, Niels; GERDES, Christoph; POOK, Elisabeth; BUCHMUeLLER, Anja; GAUGAZ, Fabienne, Zdenka; LANG, Dieter; ZIMMERMANN, Stefanie; EHRMANN, Alexander, Helmut, Michael; GERISCH, Michael; LEHMANN, Lutz; TIMMERMANN, Andreas; SCHAeFER, Martina; SCHMIDT, Georg; SCHLEMMER, Karl-Heinz; FOLLMANN, Markus; KERSTEN, Elisabeth; WANG, Vivian; GAO, Xiang; WANG, Yafeng; (801 pag.)WO2019/219517; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 578008-32-9, 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 578008-32-9 as follows.

Typical procedure for the Buchwald reaction with terf-butoxycarbonyl protected pyrazole:2-(2-Chloro-4-trifluoromethyl-phenyl)-4-(5-methyl-lH-pyrazol-3-ylamino)-2H- phthalazin- 1 -one4-Bromo-2-(2-cUoro-4-trifluoromethyl-phenyl)-2H-phthalazin-l-one (obtained from the above phthalazine-l,4-dione by bromination with POBr3 in analogy to Method R, as reported above) (0.15g, 0.37mmol), 3-amino-5-methyl-pyrazole-l- carboxylic acid tert-butyl ester (0.08Og, 0.41mmol), Cs2CO3 (0.033g, 0.34mmol), tris-(dibenzylideneacetone)-dipalladium (0.017g, 0.019mmol) and 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (0.022g, 0.037mmol) in 2 ml dry dioxane under nitrogen were heated to 100C for 18 hours, and then allowed to cool to room temperature. H2O was added and the solvent was evaporated in vacuum. The resulting solid was collected by filtration. Purification of the raw product by preparative HPLC gave the title compound (0.069g, 44% yield). 1H- EPO NMR: (400 MHz, D6-DMSO) 11.92 (IH, s), 9.34 (IH, s), 8.54 (IH, d), 8.35 (IH, d), 8.14 (IH, s), 8.01 (IH, t), 7.92 (3H, m), 6.06 (IH, s), 2.14 (3H, s); MS (ESI+) = 420.23 (M+H)+.

According to the analysis of related databases, 578008-32-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2006/32518; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 42098-25-9, name is 5-Chloro-1-methyl-4-nitro-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. name: 5-Chloro-1-methyl-4-nitro-1H-pyrazole

Example 64b 3-Fluoro-5-(4-methoxybenzyloxy)-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane To a solution of tert-butyl 3-fluoro-5-(4-methoxybenzyloxy)azepane-1-carboxylate (740 mg, 0.21 mmol) in MeOH (5 mL) was added HCl (4 M in 1,4-dioxane, 5.3 mL, 21 mmol) and the solution was stirred at room temperature for 16 hr. The solvents were removed under reduced pressure and the residue was dissolved in MeOH and loaded onto an SCX column. The column was washed with MeOH and eluted with 7 N ammonia in MeOH. The solvents were removed under reduced pressure to afford a yellow oil. To a solution of this oil in dry DMSO (15 mL) was added potassium fluoride (0.32 g, 8.4 mmol) and 5-chloro-1-methyl-4-nitro-1H-pyrazole (372 mg, 2.31 mmol) and the mixture was heated at 65 C. for 16 hr. After cooling to room temperature, the mixture was diluted with water (300 mL) and extracted with EtOAc (2*50 mL). The combined organic layers were washed with water (3*50 mL) and the solvent was removed under reduced pressure. Purification via silica gel column chromatography (20-100% EtOAc/isohexane) gave 3-fluoro-5-(4-methoxybenzyloxy)-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane as a yellow oil (300 g, 55% over two steps). 1H NMR (400 MHz, CDCl3) delta 7.33-7.23 (m, 3H), 6.89-6.86 (m, 2H), 4.82-4.66 (m, 2H), 4.49-3.93 (m, 1H), 3.81 (s, 3H), 3.30-2.99 (m, 4H), 2.95-2.74 (m, 4H), 2.35-2.03 (m, 2H), 1.98-1.83 (m, 2H).

The synthetic route of 42098-25-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GENENTECH, INC.; Hodges, Alastair James; Matteucci, Mizio; Sharpe, Andrew; Sun, Minghua; Wang, Xiaojing; Tsui, Vickie H.; US2013/79321; (2013); 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. 71229-85-1, name is 4-Bromo-1-ethyl-1H-pyrazole, A new synthetic method of this compound is introduced below., name: 4-Bromo-1-ethyl-1H-pyrazole

1003281 To a solution of compound 3 (4.3 g, 20.5 mmol) in toluene (50 mL) were added 4- bromo-1-ethyl-1H-pyrazole 4(4.0 g, 22.8 mmol), potassium phosphate (11.0 g, 51.2 mmol), N,N?-dimethylethylenediamine (722 mg, 8.2 mmol) and Cu(I)I (390 mg, 2.0 mmol) at RT underinert atmosphere. The reaction solution was purged with argon for 15 mm and then sealed the tube. The reaction mixture was heated to 140 C and stirred for 16 h. After completion of the reaction by TLC, the reaction mixture was cooed to RT, diluted with EtOAc (50 mL) and filtered. The filtrate was washed with water (40 mL), brine (40 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel chromatography; 9% EtOAc/Hexanes) to afford compound 5 (3.9 g, 63%) as a pale brown solid. 1H NMR (400 MHz, CDC13): 7.64 (s, 1H), 7.60 (s, 1H), 7.16 (d, I = 8.4 Hz, 1H), 7.01 (dd, J =8.4, 6.4 Hz, 1H), 6.12 (s, 1H), 4.25 (q, J = 7.2 Hz, 2H), 1.69-1.62 (m, 1H), 1.56 (t, J = 7.2 Hz, 3H), 0.92-0.87 (m, 2H), 0.76-0.72 (m, 2H); LC-MS (ES): 98.6%; m/z 304.3 (M + Hj; (column: X Select C-18, 50 x 3.0 mm, 3.5 tm); RT 4.23 mill; 5 mM NH4OAc: ACN; 0.8 mL/min).

The synthetic route of 71229-85-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PHARMAKEA, INC.; BAIN, Gretchen; EVANS, Jillian Frances; HUTCHINSON, John Howard; LONERGAN, David; (123 pag.)WO2016/191427; (2016); 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. 871239-17-7, name is 3-Bromo-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 3-Bromo-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid

Step H: Preparation of 2-[3-bromo-1-(2-chlorophenyl)-1H-pyrazol-5-yl]-8-methyl-4- oxo-4H-3,1-benzoxazine-6-carbonitrile; To a solution of 3-bromo-1- (2-chlorophenyl)-1H-pyrazole-5-carboxylic (i. e. the carboxylic acid product of Step E) (2.0 g, 6.29 mmol) and 2-amino-3-methyl-5- cyanobenzoic acid (i. e. the product of Step G) (1.1 g, 6.29 mmol) in acetonitrile (60 mL) at room temperature was added 3-picoline (3.2 mL, 32.7 mmol). The reaction mixture was stirred for 5 minutes and then cooled to-10 C. Methanesulfonyl chloride (1.3 mL, 16.4 mmol) was then added dropwise, and after completion of the addition the reaction mixture was warmed to room temperature. On stirring overnight at room temperature, the reaction mixture formed a solid precipitate. The solid was isolated by filtration, washed with water, dissolved in excess methylene chloride and dried (MgS04). After removal of solvent, the residue was purified by chromatography on silica gel to afford the title compound (1.9 g). ¹H NMR (CDCI3) No. 8.31 (s, 1 H), 7.73 (s,lH), 7.45-7.6 (m, 4H), 7.31 (s,lH), 1.84 (s,lH).

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 871239-17-7.

Reference:
Patent; E.I. DUPONT DE NEMOURS AND COMPANY; WO2005/118552; (2005); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 129768-28-1, These common heterocyclic compound, 129768-28-1, name is 5-(Trifluoromethyl)-1H-pyrazole-3-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.

Example 9. Procedure for the synthesis of 2-(trifluoromethyl)-5-(3-((3- (trifluo (5H)-one (34); Preparation of methyl 3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (32); 3-(Trifluoromethyl)-lH-pyrazole-5-carboxylic acid (31) (1.0 g, 8.33 mmol) was stirred inMeOH (50 mL) at rt. AcCl (1.18 mL, 16.67 mmol) was added dropwise, and the reaction stirred at reflux for 2 hours. The reaction was concentrated in vacuo and partitioned between EtOAc and saturated NaHC03 solution. The organics were dried (Na2S04) and concentrated in vacuo to give methyl 3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (32) (1.0 g, 93%); NMR (300 MHz, CDC13) delta 3.98 (s, 3H), 7.10 (s, 1 H). The product was used without purification.

Statistics shows that 5-(Trifluoromethyl)-1H-pyrazole-3-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 129768-28-1.

Reference:
Patent; ZALICUS PHARMACEUTICALS LTD.; PAJOUHESH, Hassan; HOLLAND, Richard; ZHOU, Yuanxi; ZHU, Yongbao; GRIMWOOD, Michael Edward; CHAHAL, Navjot; WO2012/61926; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 1151814-36-6,Some common heterocyclic compound, 1151814-36-6, name is 1-Cyclopropyl-1H-pyrazole, molecular formula is C6H8N2, 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 1 1-cyclopropyl-4-iodo -1H- pyrazole-pyrazole 100 mg, cyclopropyl boronic acid 253 mg, sodium carbonate 312 mg 1,2-dichloroethane in addition to 2.5 ml, was added dropwise 1,2-dichloroethane 5ml with copper acetate 267mg and 2,2-bipyridine 230mg was suspended and stirred for 4 hours at 70 C..After dilution with ethyl acetate, saturated aqueous ammonium chloride solution, washed successively with water and saturated brine, and dried over magnesium sulfate.Under reduced pressure, after the evaporation of the solvent gave 148mg as a yellow oil.

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

Reference:
Patent; NIPPON SHINYAKU COMPANY LIMITED; FUJIHARA, HIDETAKA; ASAKI, TETSUO; HORI, KATSUTOSHI; NAITO, HARUNA; (146 pag.)JP5668756; (2015); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 25016-11-9, These common heterocyclic compound, 25016-11-9, name is 1-Methyl-1H-pyrazole-4-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.

To a solution of 1-(methylsulfonyl)-5,6-dihydropyridin-2(11])-one (200 mg, 1.14 mmol, 1.0 eq), diethyl phosphorochloridate (197 mg, 1.14 mmol, 1 eq) and 1-methyl-1H-pyrazole-4- carbaldehyde (100 mg, 0.91 mmol, 0.8 eq) in THF (10 mL) at 0C was added LiHIVIDS 1M in THF (2.5 mL, 2.50 mmol, 2.0 eq). The reaction mixture was stirred at 0C for lh. Progress ofreaction was monitored by TLC. Reaction mixture was quenched by saturated ammonium chloride solution 20 mL and extracted with ethyl acetate (3 x 50 mL). Combined organic layer was washed with brine solution (50 mL) and dried over anhydrous Na2SO4. Removal of solvent under reduced pressure gave the crude which was purified by flash column chromatograpy (0-70% EtOAc-hexane) as eluent to 1- { [(E)-2-( 1-methyl- 1H-pyrazol-4-yl)ethenyl] sulfonyl } -5,6-dihydropyridin-2(11])-one (90 mg, 29.50%).LCMS: 268[M+1]1H NMR (400IVIHz, CDC13) (57.69 (s, 1 H), 7.59 (s, 1 H), 7.55 (d, 1 H), 6.91 (d, 1 H), 6.81 -6.86 (m, 1H), 5.97 (d, 1 H), 3.96 (t, 2 H), 3.92 (s, 3 H), 2.51 – 2.57 (m, 2 H),

The synthetic route of 25016-11-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AURANSA INC.; PROTTER, Andrew, Asher; GREEN, Michael, John; CHANG, Hak, Jin; PHAM, Son, Minh; CHAKRAVARTY, Sarvajit; LUEDTKE, Gregory, R.; (254 pag.)WO2019/103897; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 52222-73-8, 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. 52222-73-8 name is 4-(Trifluoromethyl)-1H-pyrazole, 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.

[00564] Intermediate 57a: ethyl 2-[4-(trifluoromethyl)pyrazol-1 -yI]acetate [00565] 4-(Trifluoromethyl)-1 H-pyrazole (100mg, 0.73mmol) and potassium carbonate (305mg, 2.2Ommol) were left to stir in MeCN (2mL) for 30 minutes at room temperature before the addition of ethyl bromoacetate (0.l2mL, 1.lOmmol). The reaction mixture was then heated to 60C and left to stir at this temperature for 2 hours. The reaction was allowed to cool to room temperature andquenched by the addition of water (2OmL) and this solution was extracted with EtOAc (3 x 2OmL).The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to giveethyl 2-[4-(trifluoromethyl)pyrazol-1-yl]acetate (1 60mg, 0.72mmol, 100% yield) as a yellow oil.1H NMR (CDCI3,400MHZ) O/ppm: 7.82 (1H, 5), 7.77 (1H, 5), 4.95 (2H, 5), 4.29 (2H, q, J= 7.1Hz),1.32 (3H, t, J= 7.1Hz).MS Method 2: RT: 1.54 mi mlz 222.9 [M+H]

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

Reference:
Patent; REDX PHARMA PLC; ARMER, Richard; BELFIELD, Andrew; BINGHAM, Matilda; JOHNSON, Alice; MARGATHE, Jean-Francois; AVERY, Craig; HUGHES, Shaun; MORRISON, Angus; (278 pag.)WO2016/51193; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics