Category: pyrazoles-derivatives

151521-49-2, name is 4-Isopropyl-1H-pyrazol-5-amine, 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. Computed Properties of C6H11N3

A mixture of diethyl 2-(ethoxymethylene)propanedioate (621.89 mg, 2.88 mmol, 581.21 L, 1 eq), 4-isopropyl-1H-pyrazol-5-amine (400 mg, 2.88 mmol, 1 eq) in AcOH (3 mL) was degassed and purged with N2 for 3 times. The mixture was stirred at 120 C for 2 h under N2; atmosphere. The reaction mixture was cooled to 0 C and filtered. The solid was washed with ethanol and petroleum ether and dried under reduced pressure to give ethyl 7-hydroxy-3-isopropyl-pyrazolo[l,5- a]pyrimidine-6-carboxylate (700 mg, 2.65 mmol, 92.3% yield, 94.5% purity) as a white solid which was used in the next step without further purification. NMR (400 MHz, CD3OD) delta ppm 8.55 (s, 1H), 7.91 (s, 1H), 4.34 (q, J = 7.2 Hz, 2H), 3.11 (m, 1H), 1.40-1.31 (m, 9H); ES-LCMS m/z 250.2 [M+H].

The synthetic route of 151521-49-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KYN THERAPEUTICS; CASTRO, Alfredo C.; EVANS, Catherine Anne; (632 pag.)WO2018/195397; (2018); A2;,
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. 51985-95-6, name is Methyl 5-hydroxy-1-methyl-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H8N2O3

6. 5-Difluoromethoxy-3-methoxycarbonyl-1-methylpyrazole 67.6 g (0.43 mol) 5-Hydroxy-3-methoxycarbonyl-1-methylpyrazole and 299.2 g (2.17 mol) potassium carbonate was dissolved in 1500 ml dimethylformamide and heated to 70° C. At this temperature chlorodifluoromethane was introduced over 2 hours and the mixture stirred at 80° C. for 1.5 hours. The reaction mixture was added to water and extracted 6 times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride and dried over magnesium sulfate. The reaction solution was concentrated. Yield: 80.6 g=90.3percent of theory.

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; Hoechst Schering AgrEvo GmbH; US5580986; (1996); A;,
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. 113100-53-1, name is 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, A new synthetic method of this compound is introduced below., Formula: C6H5F3N2O2

Example 2 : Preparation of N-{2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-2-methylpropyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (compound 24); 104 mg of 2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-2-methyl-1-propanamine hydrochloride, 40 muL of triethylamine, 62 mg of 3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, 0.13 g of 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (0.00054 mol) are stirred in 2 mL of methanol at room temperature overnight. The reaction mixture is concentrated to dryness and purified on silica to yield to 95 mg of N-{2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-2-methylpropyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (59%). Mass spectrum: [M+1] = 429.

The synthetic route of 113100-53-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bayer CropScience S.A.; EP1548007; (2005); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 152120-54-2, 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 152120-54-2 as follows.

Compound 6 (1.47 kg) is dissolved in methanol (11.6 kg), then 10% Pd-C (143 g) is added under nitrogen atmosphere. The resulting reaction mixture is stirred 2.5 hours under hydrogen at ambient pressure, and then catalyst is removed by filtration. To the filtrate, 1N HCl (2 L), triethylamine (420 g) and di-boc-guanylpyrazole (0.70 g) are added in order. The resulting reaction mixture is stirred at room temperature for 102 minutes. Then it is evaporated, followed by dilution with ethyl acetate (10.7 kg). The organic layer washed with sodium chloride solution, dried over sodium sulfate and evaporated to dryness. The crude compound 8 is purified by column chromatography with 1.9 kg of silica gel and ethyl acetate/ dichloromethane to methanol/dichloromethane. Yield: 1.19 kg (62.3%), expected HPLC purity: about 96.4%

According to the analysis of related databases, 152120-54-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CELLCEUTIX CORPORATION; MENON, Krishna; (75 pag.)WO2016/133733; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 181585-93-3,Some common heterocyclic compound, 181585-93-3, name is Methyl 5-nitro-1H-pyrazole-3-carboxylate, molecular formula is C5H5N3O4, 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.

Step3: Methyl 5,7-dihydroxy-6-phenylpyrazolo[1 ,5-a]pyrimidine-2-carboxylate; A solution of 5.Og Methyl 3-amino-1 H-pyrazole-5-carboxylate, 8.3ml_ diethyl- phenylmalonate and 5OmL diisopropylethylamine in 5OmL DMF was heated to 1500C for 40h. The solvent was removed, the solid residue was dissolved in 2- propanol the mixture was stirred for 3 hours. The desired product was filtered, dried and was used without further purification. MS (M+1): 286 Characteristic 1 H NMR (300MHz, d6-DMSO) signals: 6.0 (s, 1 H); 3.8 (s, 3H)

The synthetic route of 181585-93-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER SCHERING PHARMA AKTIENGESELLSCHAFT; VENNEMANN, Matthias; MAIER, Thomas; HOeLDER, Swen; BENEKE, Gerrit; DEHMEL, Florian; ZUeLCH, Armin; STRUB, Andreas; BECKERS, Thomas; INCE, Stuart; REHWINKEL, Hartmut; LIU, Ningshu; BOeMER, Ulf; WO2010/91808; (2010); 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. 612511-81-6, name is (1-Methyl-1H-pyrazol-3-yl)methanamine, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 612511-81-6

General procedure: N,N-Diisopropylethylamine (3.0?4.0 eq) was added to 8-methoxyquinoline-3-carboxylic acid (1.0 eq) in solvent (dichloromethane, tetrahydrofuran,or N,N-dimethylformamide, 0.05 to 0.2 M) at room temperature. Then, 1-((dimethylamino)(dimethyliminio)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine 3-oxide hexafluorophosphate(V)(1.0?1.5 eq) was added and the reaction mixture was stirred for five minutes. Then, amine (1.0 ? 2.0 eq) was added and the reaction mixture was stirred for one to sixteen hours. 10percent Aqueous citric acid was added and the reaction mixture was extracted with dichloromethane, washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered,and concentrated. The resulting residue was purified by RP HPLC or silica gel chromatography to give the quinoline-3-carboxamide (1percent-95percent yield).

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 612511-81-6.

Reference:
Article; Deaton, David N.; Do, Young; Holt, Jason; Jeune, Michael R.; Kramer, H. Fritz; Larkin, Andrew L.; Orband-Miller, Lisa A.; Peckham, Gregory E.; Poole, Chuck; Price, Daniel J.; Schaller, Lee T.; Shen, Ying; Shewchuk, Lisa M.; Stewart, Eugene L.; Stuart, J. Darren; Thomson, Stephen A.; Ward, Paris; Wilson, Joseph W.; Xu, Tianshun; Guss, Jeffrey H.; Musetti, Caterina; Rendina, Alan R.; Affleck, Karen; Anders, David; Hancock, Ashley P.; Hobbs, Heather; Hodgson, Simon T.; Hutchinson, Jonathan; Leveridge, Melanie V.; Nicholls, Harry; Smith, Ian E.D.; Somers, Don O.; Sneddon, Helen F.; Uddin, Sorif; Cleasby, Anne; Mortenson, Paul N.; Richardson, Caroline; Saxty, Gordon; Bioorganic and Medicinal Chemistry; vol. 27; 8; (2019); p. 1456 – 1478;,
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 5932-27-4 as follows. Recommanded Product: Ethyl 1H-pyrazole-3-carboxylate

To a solution of ethyl 3-pyrazolecarboxylate (1.0 g) in N,N-dimethylformamide (7.0 mL) was added N-iodosuccinimide (1.6 g), and the mixture was stirred at room temperature for 1 hour, warmed to 60C, and then stirred for 0.5 hours. The reaction solution was returned to room temperature, saturated aqueous sodium bicarbonate and sodium sulfite were added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and then dried over sodium sulfate. The solvent was removed under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain a compound 0215-1 (1.0 g) as a pale yellow solid.

According to the analysis of related databases, 5932-27-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; FUJIFILM Corporation; FURUYAMA, Hidetomo; KURIHARA, Hideki; FURUYA, Kentarou; TERAO, Takahiro; SEKINE, Shinichirou; NAKAGAWA, Daisuke; EP2727920; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 694-48-4,Some common heterocyclic compound, 694-48-4, name is 1,3-Dimethyl-1H-pyrazole, molecular formula is C5H8N2, 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.

In a 5 L reactor, equipped with a stirrer, a reflux condenser, an argon inlet, thermometer and dropping funnel, 1,3-dimethyl-1H-pyrazole(500 g, 5.2 mol) was added slowly with stirring to acetic anhydride (1950 mL, 2125 g, 20.8 mol), while maintaining the temperature below 45 C. Concd H2SO4(50 mL, 92 g, 0.94 mol) was added with cooling and stirring and the mixture then was gradually heated to reflux and held at reflux for 6 h. The mixture was then cooled, evaporated at 70 C/7 Torr, and treated with crushed ice (2 kg). By carefully addition of 40% NaOH solution, the pH of the reaction mixture was adjusted to pH 8, then the organic phase was separated and the aqueous phase was extracted with CH2Cl2(2 × 1000 mL).The combined organic phases were washed successively with H2O(500 mL) and brine (500 mL), and dried over MgSO4. The solvent was removed at 7 Torr, and the residue was distilled (110-112 C/10 Torr) to afford the target ketone (452 g, 63%) as thick, light yellow oil, which crystallized upon standing.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1,3-Dimethyl-1H-pyrazole, its application will become more common.

Reference:
Article; Taydakov, Ilya V.; Krasnoselskiy, Sergey S.; Synthesis; vol. 45; 15; (2013); p. 2188 – 2192;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 37687-24-4, name is Diethyl 3,5-pyrazoledicarboxylate, molecular formula is C9H12N2O4, 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. Formula: C9H12N2O4

Example 27; Preparation of (5R, 6Z)-7-oxo-6- [ (4-oxo-6, 7-dihydro-4H-pyrazo . o [5, 1-c] [1, 4] oxazin-2- yl) methylene]-4-thia-1-azabicyclo [3. 2. 0] hept-2-ene-2-carboxylic Acid. Step 1: Diethyl 1- (2-frtert-butyl (dimethvl) silvlloxylethyl)-1H-ayrazole-3, 5- dicarboxvlate To a solution of diethyl 3, 5-pyrazoledicarboxylate (2.17 g, 10 mmol) in acetonitrile (10 ml), under nitrogen, was added potassium carbonate (2.07 g, 15 mmol), and 2- bromoethoxy-t-butyldimethylsilane (2.90 g, 12 mmol). The mixture was stirred at reflux for 18 hr. It was then cooled to room temperature, diluted with ethyl acetate (20 ml), and filtered through Magnesol. The filter pad was eluted wtih 2 x 10 mi of ethyl acetate, and the combined filtrate was evaporated. The residue was dissolved in hexanes and passed through a column of silica gel (70 g). After eluting with hexanes (100 ml), the column was eluted with ethyl acetate. The ethyl acetate eluent was evaporated to give 3.71 g of a colorless oil ; MS m/e 371 (MH+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 37687-24-4, its application will become more common.

Reference:
Patent; WYETH; WO2003/93277; (2003); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1280210-79-8, 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. 1280210-79-8 name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-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.

To a solution of tert-butyl 4,6-dihydropyrrolo[3,4- c]pyrazole-5(2H)-carboxylate (15.0 g, 71.8 mmol) in DMF (150 mL) was added NaH (60% in mineral oil) (8.6 g, 215.4 mmol) while the reaction mixture was cooled with an ice bath. When the addition was complete, the resulting mixture was allowed to warm to room temperature and was stirred at room temperature for 30 min. At this point, l-bromo-2- methoxyethane (19.8 g, 143.6 mmol) was added into the reaction mixture, and stirring was continued at room temperature for 2 h. The reaction mixture was then quenched with water (300 mL), and extracted with EtOAc (150 mL x 3). The combined organic layer was washed with brine (100 mL x 3), dried over anhydrous Na2S04 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM : MeOH = 100 : 1 ~ 30 : 1) to give a mixture of 122 and 122-A (19.0 g, 99%) as a colorless oil. MS 268.2 [M + H]+. [0072] Synthesis of 123 and 123-A. To a solution of 122 and 122-A (6.5 g, 24.3 mmol) in DCM (60 mL) cooled with an ice bath was added TFA (30 mL). The reaction mixture was stirred at room temperature for 1 h, whereupon the solvent was removed in vacuo to give 123 and 123-A as a crude product mixture which was used directly in the next step without further purification. MS 168.1 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; RODIN THERAPEUTICS, INC; FULLER, Nathan, Oliver; LOWE, John, A.; (45 pag.)WO2019/32528; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics