Day: September 14, 2021

Reference of 89088-55-1, 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. 89088-55-1, name is 5-Bromo-1-methyl-1H-pyrazol-3-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (158 mg, 0.68 mmole) in 10 mL of CH2Cl2, was added 1-methyl imidazole (0.14 mL, 2.5 equiv.) at 0-5 C. under nitrogen atmosphere. The reaction mixture was stirred for 10 min at 0-5 C. and then added methane sulfonyl chloride (0.06 mL, 1.2 equiv) at the same temperature. It was stirred for 1 h at 0-50 C. Then 5-bromo-1-methyl-1H-pyrazol-3-amine (120 mg, 1 equiv) was added, and stirred for 18 h at room temperature. Water (10 mL) was added to the reaction mixture, layers were separated and aqueous layer was extracted with DCM (3×10 mL). The combined organic layer was washed with 1N HCl (10 mL), followed by Sat NaHCO3(10 mL) and with brine (10 mL). Combined organic layer was dried over Na2SO4, concentrated and ready to use in step-2.

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, 5-Bromo-1-methyl-1H-pyrazol-3-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAK, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; (905 pag.)WO2017/35353; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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 52222-73-8 as follows. SDS of cas: 52222-73-8

Intermediate (1): (4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanol A mixture of (4-iodophenyl)methanol (1030 mg, 4.41 mmol), 4-(trifluoromethyl)-1H-pyrazole (600 mg, 4.41 mmol), copper (I) iodide (168 mg, 0.882 mmol), trans-4-hydroxy-L-proline (231 mg, 1.76 mmol) and cesium carbonate (2900 mg, 8.82 mmol) in dimethylsulfoxide (7.5 mL) was heated to 85 C. for 20 hours. The mixture was diluted with water and extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (0-45% ethyl acetate in heptane), gave (4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanol. 1H NMR (400 MHz, CDCl3, delta): 8.16 (s, 1H), 7.89 (s, 1H), 7.65 (d, J=8.39 Hz, 2H), 7.47 (d, J=8.39 Hz, 2H), 4.74 (d, J=5.66 Hz, 2H), 1.85 (t, J=5.86 Hz, 1H).

According to the analysis of related databases, 52222-73-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PFIZER INC.; US2012/202834; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 20154-03-4, 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. 20154-03-4 name is 3-(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.

Step 1: Preparation of 4-iodo-3-(truoromethyl)-1H-pyrazole. To a solution of 3- (trifluoromethyl)-1H-pyrazole (500 mg, 3.7 mmol) in 50percent 112S04 at 0 °C was added MS (992 mg, 4.4 mmol). The suspension was stirred at 0°C for 10 mm and then at r.t. for 3 hr. The resulting mixture was quenched with water (50 mL), and then stirred overnight. The precipitate was collected by filtration and dried to afford 4-iodo-3-(trifluoromethyl)-1H-pyrazole.LC-MS:m/z 263 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(Trifluoromethyl)-1H-pyrazole, and friends who are interested can also refer to it.

Reference:
Patent; AGIOS PHARMACEUTICALS, INC.; KONTEATIS, Zenon D.; POPOVICI-MULLER, Janeta; TRAVINS, Jeremy M.; ZAHLER, Robert; CAI, Zhenwei; ZHOU, Ding; WO2015/3640; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 478968-48-8, 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 478968-48-8 as follows.

A mixture of Cul (88 mg, 0.46 mmol, 0.10 equiv), L-proline (108 mg, 0.94 mmol, 0.20 equiv), potassium carbonate (1.3 g, 9.41 mmol, 2.00 equiv), ethyl 3-methoxy-li7-pyrazole-4-carboxylate (800 mg, 4.70 mmol, 1.00 equiv), and 5-bromo-2-(trifluoromethyl)pyrimidine (1.28 g, 5.64 mmol, 1.20 equiv) in DMSO (5 mL) was stirred overnight at 100 C under nitrogen. The reaction mixture was diluted with 40 mL of water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/petroleum ether (1 :5) to afford the title compound (580mg, 39%) as a white solid.

According to the analysis of related databases, 478968-48-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; VERMA, Vishal; SHORE, Daniel; VOLGRAF, Matthew; ESTRADA, Anthony A.; LYSSIKATOS, Joseph; (153 pag.)WO2018/15410; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 866837-96-9, 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. 866837-96-9 name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, 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.

Pyridine (12.9 mL, 161 mmol) was added to a solution of ethyl 5-amino-1-phenyl-1H- pyrazole-3-carboxylate (9.32 g, 40.3 mmol) and 5-bromo-2-chlorobenzoic acid (10.4 g,44.3 mmol) in 2-methyl-tetrahydrofuran (100 mL). The reaction was heated to 85C before the addition of propylphosphonic anhydride (38.5 mL, 60.4 mmol, 50% solution in EtOAc) drop-wise. The reaction was heated at 85C for 16 hours before cooling to room temperature. The organic solution was washed with saturated aqueous sodium hydrogen carbonate solution (3 x 25 mL), saturated brine (30 mL) and concentrated invacuo. The resulting solid was triturated with TBME (5 x 50 mL) to afford the titlecompound (13.7 g, 76%).1H NMR (400MHz, CDCI3): O ppm 1.42 (t, 3H), 4.44 (q, 2H), 7.25 (d, 1H), 7.39 (5, 1H),7.51 (m, 5H), 8.02 (d, 1H), 8.43 (5, 1H).LCMS Rt = 3.13 minutes MS mlz 448 [M+H]

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; PFIZER INC.; BAGAL, Sharanjeet Kaur; CUI, Jingrong Jean; GREASLEY, Samantha Elizabeth; LUNNEY, Elizabeth Ann; MCALPINE, Indrawan James; NAGATA, Asako; NINKOVIC, Sacha; OMOTO, Kiyoyuki; SKERRATT, Sarah Elizabeth; STORER, Robert Ian; WARMUS, Joseph Scott; WO2015/170218; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 39806-90-1,Some common heterocyclic compound, 39806-90-1, name is 4-Iodo-1-methyl-1H-pyrazole, molecular formula is C4H5IN2, 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.

General procedure: 4-Iodo-1-methyl-1H-pyrazole 1 (101 mg, 0.5 mmol) and phenylboronic 2 (59 mg, 0.5 mmol) were dissolved in DME (3 mL) and H2O (1.2 mL) in a microwave vial under a nitrogen atmosphere. Pd(PPh3)4 (2 mmol%, 11.6 mg) and Cs2CO3 (407.3 mg, 1.25 mmol) were added, and the reaction mixture was irradiated in a microwave apparatus at 90 C for 5-12 min. After the reaction mixture was cooled to ambient temperature, the product was concentrated, and the crude mixture was purified by silica gel column chromatography using petroleum ether/acetone as eluent to give the title compound.

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

Reference:
Article; Cheng, Hua; Wu, Qiong-You; Han, Fan; Yang, Guang-Fu; Chinese Chemical Letters; vol. 25; 5; (2014); p. 705 – 709;,
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. 345637-71-0, name is 2-(5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acid, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H7F3N2O2

To a solution of 5-methyl-3-(trifluoromethyl)-lH-pyrazole-l -acetic acid (0.8 g, 3.8 mmol) in dichloromethane (10 mL) was added oxalyl chloride (2.4 g, 19.2 mmol) and two drops of iV.TV-dimethylformamide, resulting in slight exothermicity. The reaction mixture was then heated at reflux for 15 minutes. The reaction mixture was concentrated in vacuo, and the residue was suspended in tetrahydrofuran (10 mL) and treated with a solution of 2-(4-piperidinyl)-4-thiazolecarboxaldehyde’ monohydrochloride (i.e. the product of Example 2, Step A) (1.1 g, 5.1 mmol) in tetrahydrofuran (10 mL), followed by dropwise addition of triethylamine (1.2 g, 11.9 mmol). The reaction mixture was stirred overnight at room temperature and then partitioned between 1 N aqueous hydrochloric acid and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with additional ethyl acetate (2 x 30 mL). The combined organic layers were washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, and brine. The organic layer was dried (MgSC^) and evaporated under reduced pressure to give 0.8 g of the title compound as a yellow oil. IH NMR (CDCl3) delta 1.79-1.90 (m, 2H)5 2.18-2.29 (m, 2H), 2.33 (s, 3H), 2.87-2.94 (m, IH)5 3.28-3.40 (m, 2H), 4.05-4.15 (m, IH), 4.56-4.64 (m, IH), 4.99-5.02 (m, 2H), 6.35 (s, IH), 8.12 (s, IH)5 IO-Ol (s, IH).; To a solution of 5-methyl-3-(trifluoromethyl)-li’-pyrazole-l -acetic acid (0.5 g,2.4 mmol) in dichloromethane (4 mL) was added oxalyl chloride (0.3 mL, 3.6 mmol) and one drop of N,LambdaT-dimethylformamide, resulting in slight exothermicity. The reaction mixture was then heated at reflux for 15 minutes. The reaction mixture was evaporated, and the resulting residue was suspended in dichloromethane (4 mL) and treated with a solution of 4-(4-ethenyl-2-thiazolyl)piperidine (i.e. the product of Example 4, Step B) (302 mg,1.5 mmol) in dichloromethane (2 mL), followed by addition of triethylamine (0.32 mL, 2.3 mmol). The reaction mixture was stirred overnight at room temperature, then concentrated, and purified by column chromatography on silica gel using 30-40 % ethyl acetate in hexanes as eluant to give 414 mg of the title compound as a white solid. IH NMR (CDCl3) 6 1.78 (m, 2H), 2.18 (m, 2H), 2.32 (s, 3H), 2.90 (br t, IH), 3.30 (m, 2H),4.03 (d, IH), 4.55 (d, IH), 5.00 (m, 2H), 5.35 (d, IH), 6.02 (d, IH), 6.33 (s, IH), 6.68 (dd,IH)5 7.01 (s, IH).

According to the analysis of related databases, 345637-71-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; WO2008/13622; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 113100-53-1, name is 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, molecular formula is C6H5F3N2O2, 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. Quality Control of 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

e) 1-methyl-3-trifluoromethyl-lH-pyrazole-4-carboxylic acid (2.5g, 13mmol) was dissolved in dichloromethane (25ml) containing 5 drops of N,N-dimethylformamide. A solution of oxalyl chloride (1.8g, 14mmol) in dichloromethane (5ml) was added dropwise at room temperature. This mixture was stirred for 2hours at the same temperature and was subsequently slowly added to a mixture of 2-[5-(3,3-dimethyl-but-1-ynyl)-thiophen-2-yl]- phenylamine (3.3g, 13mmol) and triethylamine (2.0g, 20mmol) in dichloromethane (30ml). After stirring the reaction mixture for 8hours at room temperature, it was poured on ice and extracted with dichloromethane. The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated. The remaining oil was purified by silica gel chromatography using ethyl acetate and hexane as eluents, giving Compound No. lai.098 (1.2g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 113100-53-1, its application will become more common.

Reference:
Patent; SYNGENTA PARTICIPATIONS AG; WO2005/123722; (2005); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1029413-51-1, The chemical industry reduces the impact on the environment during synthesis 1029413-51-1, name is 4-Amino-1-(1-boc-azetidin-3-yl)-1H-pyrazole, I believe this compound will play a more active role in future production and life.

C) tert-butyl 3-(4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate To a solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (300 mg) obtained in Step E of Example 103, tert-butyl 3-(4-amino-1H-pyrazol-1-yl)azetidine-1-carboxylate (300 mg) obtained in Step B of Example 131, cesium carbonate (740 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (110 mg) in tetrahydrofuran (10 mL) was added tris(dibenzylideneacetone)dipalladium(0) (105 mg), and the mixture was stirred at 90C for 10 hr under argon atmosphere. The solvent was evaporated under reduced pressure, and the reaction mixture was poured into water, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) to give the title compound (310 mg). MS(ESI+): [M+H]+ 465.4.

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-Amino-1-(1-boc-azetidin-3-yl)-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Takeda Pharmaceutical Company Limited; TSUKAMOTO, Tetsuya; OHBA, Yusuke; YUKAWA, Takafumi; NAGAMIYA, Hiroyuki; KAMEI, Taku; TOKUNAGA, Norihito; SAITOH, Morihisa; OKABE, Atsutoshi; EP2832734; (2015); 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. 930-36-9, name is 1-Methylpyrazole, A new synthetic method of this compound is introduced below., Safety of 1-Methylpyrazole

N-methylpyrazole (1.0 g, 1 eq.) was dissolved in N,N-dimethylformamide (2.8 ml, 3 eq.), phosphorus oxychloride (1.3ml, 1.2 eq.) was added dropwise at 90 C over about 1 h. The mixture was reacted for another 2 h and then cooled. The reaction liquid was poured into iced water and adjusted with 10% aqueous sodium hydroxide solution to PH 4?5, extracted four times with dichloromethane, rinsed with water twice, and separated by column chromatography to give 600 mg product

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; Shanghai Institute Of Materia Medica Chinese Academy of Sciences; SHEN, Jianhua; WANG, Yiping; CHEN, Xinde; XU, Wenwei; WANG, Kai; (84 pag.)EP3239135; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics