Category: pyrazoles-derivatives

Reference of 23170-45-8, These common heterocyclic compound, 23170-45-8, name is Methyl 3-methyl-1H-pyrazole-4-carboxylate, 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.

Synthesis of methyl l-benzyl-S-methyl-lH^yrazole-4-carboxylate. [00186] To a solution of methyl 3-methyl-lH-pyrazole-4-carboxylate (280 mg, 2 mmol) in N, N-dimethylformamide (30 mL) was added (bromomethyl)benzene (0.34 g, 2 mmol) and potassium carbonate (0.55 g, 4 mmol). The mixture was stirred at 20 C and stirred for 12 hours. The solvent was evaporated in vacuo and the residue was purified by CXTH (Column:Dsisol, 10muMu, CI 8, 250 mm*50 mm; Mobile: aeetonitrile(0.1% formic acidj-water (0.1% formic acid), acetonitrile from 30% to 70% in 80 minutes; oven; 20C; flow rate: 50 mL/minute, wavelength; 214 nm) to give crude methyl 1 -benzyl-5-meth.yl- lH-pyrazole-4-earboxylate (200 mg, 42%). LRMS (M + H+) m/z calcd. 230.1 1 ; found 230.

Statistics shows that Methyl 3-methyl-1H-pyrazole-4-carboxylate is playing an increasingly important role. we look forward to future research findings about 23170-45-8.

Reference:
Patent; CONSTELLATION PHARMACEUTICALS; ALBRECHT, Brian, K.; AUDIA, James, Edmund; COOK, Andrew, S.; DAKIN, Les, A.; DUPLESSIS, Martin; GEHLING, Victor, S.; HARMANGE, Jean-Christophe; NAVESCHUK, Christopher, G.; VASWANI, Rishi, G.; WO2013/120104; (2013); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1453-58-3, 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. 1453-58-3 name is 3-Methylpyrazole, 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.

Potassium /-butoxide (3.9 g, 0.33 mmol) was dissolved in DMSO (25 mL). To this solution was added 3 -methyl pyrazole (2.7 g, 0.33 mmol) and the reaction was heated at 50 °C for 30 min. l-Bromo-4-chloro-2-fluorobenzene (4.6 g, 0.22 mmol) was then added and the reaction was stirred at 50 °C for 16 h. The reaction was cooled to RT and extracted with water and EtOAc, washed with brine, and dried over Na2S04) filtered and concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtO Ac/heptane) provided l-(2- bromo-5-chlorophenyl)-3-methyl-lH-pyrazole and l-(2-bromo-5-chloroplienyl)-5-methyl-lH- pyrazole as a 4: 1 mixture that was used in the next step directly,

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

Reference:
Patent; KAROS PHARMACEUTICALS, INC.; DE LOMBAERT, Stephane; GOLDBERG, Daniel R.; BRAMELD, Kenneth; SJOGREN, Eric Brian; SCRIBNER, Andrew; WO2015/35113; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 26621-44-3, 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. 26621-44-3 name is 3-Nitro-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.

[313] To a 0 C solution of 3-nitro-1H-pyrazole (250.0 g, 2.17 mol, 1.0 eq) in anhydrous DMF (2.5 L; 10.2 vol eq) under nitrogen was added NaH (95.42 g of 60 %w/w, 2.39 mol, 1.1 eq) in batches over 30 min while maintaining temperature below 8 C. The mixture was stirred for 1 h then 2,4-difluoropyridine (300 mL, 3.29 mol, 1.5 eq) was added, and the reaction was warmed to room temperature and stirred for approximately 16 hours (h). The reaction mixture was diluted with water (12.5 L) and stirred vigorously for 1 h. The off-white solid was collected by vacuum filtration. The solid was re-suspended in water (2 L) and filtered, and this step was repeated once further. The product was dried under vacuum, then suspended in heptane (4L), stirred 3 h at room temperature, and filtered. The solid was washed with two further portions of heptane (2 L each) and dried under vacuum to provide 2-fluoro- 4-(3-nitro-1H-pyrazol-1-yl)pyridine (426.3 g of 92% purity, 87% yield). 1H NMR (400 MHz, DMSO-d6) delta 9.01 (d, J = 2.8 Hz, 1H), 8.45 (d, J = 5.7 Hz, 1H), 7.95 (ddd, J = 5.7, 1.9, 1.2 Hz, 1H), 7.81 (t, J = 1.4 Hz, 1H), 7.46 (d, J = 2.8 Hz, 1H) ppm. ESI-MS m/z calc. 208.04, found 209.01 (M+1).

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

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARIFSON, Paul, S.; COME, Joh, H.; COURT, John, J.; GALE-DAY, Zachary; GU, Wenxin; JACKSON, Katrina, L.; MAGAVI, Sanjay, Shivayogi; NANTHAKUMAR, Suganthini, S.; RONKIN, Steven, Michael; SWETT, Rebecca, Jane; TANG, Qing; (383 pag.)WO2018/107056; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 158001-28-6, 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. 158001-28-6, name is 5-Amino-1-(tert-butyl)-1H-pyrazole-4-carbonitrile belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Preparation #26. 3-Bromo-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine A suspension of 5-amino-1-tert-butyl-1H-pyrazole-4-carbonitrile (8.67 g, 0.0528 mol) in formamide (100 mL) was heated at 180 C. for about 4 hours. The reaction mixture was cooled, poured into ice water (200 mL), and the product was extracted with ethyl acetate (4*80 mL). The combined organic layers were dried over magnesium sulfate, and the solvent was removed under reduced pressure. The residue was taken up in ether (35 mL) and the precipitate was filtered, washed with ether (50 mL), and dried under reduced pressure to afford 1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (3.22 g, 0.0169 mol) as a white solid; RP-HPLC (30% to 95% acetonitrile/0.01M aqueous ammonium acetate, buffered to pH 4.5, over 4.5 min at 0.8 mL/min; lambda=190-700 nm; Genesis C18, 120 A, 3 mum, 30*4.6 mm column) Rt 1.38 min.

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-Amino-1-(tert-butyl)-1H-pyrazole-4-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Wishart, Neil; Friedman, Michael; Arnold, Lee D.; Yang, Bryant; Fix-Stenzel, Shannon R.; Ericsson, Anna; Michaelides, Michael R.; Qian, Xiao-Dong; Holms, James H.; Steinman, Douglas H.; Tian, Zhengping; Wittenberger, Steven J.; US2006/25383; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 131797-35-8, A common heterocyclic compound, 131797-35-8, name is 5-Chloro-3-(trifluoromethyl)-1H-pyrazole, molecular formula is C4H2ClF3N2, 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 ethyl 2-[7-(chloromethyl)-2-methyl-5-oxo-5H-[l,3]thiazolo[3,2-a]pyrimidin- 3-yl]propanoate (2 g, 6.35 mmol) in acetonitrile (30 mL) was added 5-chloro-3-(trifluoromethyl)-lH- pyrazole (1.1 g, 6.45 mmol), potassium iodide (1.06 g, 6.39 mmol), and potassium carbonate (2.2 g, 15.9 mmol). The resulting mixture was stirred for 2 h at 90 C, cooled to room temperature and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/petroleum ether (1/4) to afford ethyl 2-(7-[[5-chloro-3-(trifluoromethyl)-lH-pyrazol-l-yl]methyl]- 2-methyl-5-oxo-5H-[l,3]thiazolo[3,2-a]pyrimidin-3-yl)propanoate (2.9 g, crude) as a brown solid. LCMS (ESI): M+H+ = 449.0.

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; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; YU, Jiang; WU, Guosheng; YUEN, Po-Wai; VILLEMURE, Elisia; SCHWARZ, Jacob; LY, Cuong; SELLERS, Benjamin; VOLGRAF, Matthew; WO2015/52226; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 10010-93-2,Some common heterocyclic compound, 10010-93-2, name is 3-Methyl-5-(trifluoromethyl)-1H-pyrazole, molecular formula is C5H5F3N2, 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: In a Biotage tube, the relevant trifluoromethylpyrazole (1 mmol) and sodium hydroxide (0.2 g, 5 mmol) were stirred in ethanol/water 1:3 (1.2 mL). The tube was sealed and heated at 120 or 150 C, as mentioned in the text for 1 h in a microwave oven. The resulting suspension was dissolved in water; the aqueous phase was washed with dichloromethane twice and made acidic with 2 N hydrochloric acid. This was extracted with ethyl acetate twice; the organic layer was washed with brine, dried over magnesium sulfate, and concentrated to dryness to yield the corresponding acid as described below. CAUTION: the reaction conditions used lead to the release of fluorine ions that attack the glass tubes. Never recycle the reaction tubes as their resistance toward pressure and temperature may have been weakened in a process, which is releasing sodium fluoride.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Methyl-5-(trifluoromethyl)-1H-pyrazole, its application will become more common.

Reference:
Article; Ermolenko, Mikhail S.; Guillou, Sandrine; Janin, Yves L.; Tetrahedron; vol. 69; 1; (2013); p. 257 – 263;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 1192-21-8, 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. 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

BrettPhos 3rd generation precatalyst (12.44 mg, 0.02 mmol) was added to CS2CO3 (304 mg, 0.93 mmol), 1 -methyl- lH-pyrazol-5-amine (91 mg, 0.93 mmol) and (5)-2-(2-chloro-5- methylpyrimidin-4-yl)-7-(3-(difluoromethyl)benzyl)-6-methyl-6,7-dihydroimidazo[l,2- a]pyrazin-8(5H)-one (Intermediate 69; 130mg, 0.31 mmol) in 1,4-dioxane (5 mL) under nitrogen. The resulting mixture was stirred at 100 °C for 4 hours. The solvent was then removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 6percent MeOH in DCM. Pure fractions were evaporated to dryness to afford a residue. This residue was purified further by preparative HPLC (XSelect CSH Prep C18 OBD column, 5mu silica, 19 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1percent Formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (5)-7-(3- (difluoromethyl)benzyl)-6-methyl-2-(5-methyl-2-((l-methyl-lH-pyrazol-5- yl)amino)pyrimidin-4-yl)-6,7-dihydroimidazo[l,2-a]pyrazin-8(5H)-one (Example 21; 85 mg, 57.1percent) as a white solid. lH NMR (300 MHz, DMSO, 23 °C) delta 1.12 (3H, s), 2.40 (3H, s), 3.70 (3H, s), 3.90-4.10 (1H, m), 4.36-4.44 (3H, m), 5.14 (1H, d), 6.29 (1H, d), 7.04 (1H, t), 7.33 (1H, d), 7.50-7.59 (4H, m), 7.93 (1H, s), 8.32 (1H, s), 9.21 (1H, s). m/z (ES+), [M+H]+ = 479.

The synthetic route of 1-Methyl-1H-pyrazol-5-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WARD, Richard, Andrew; JONES, Clifford, David; SWALLOW, Steven; GRAHAM, Mark, Andrew; DOBSON, Andrew, Hornby; MCCABE, James, Francis; (223 pag.)WO2017/80979; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 360056-45-7,Some common heterocyclic compound, 360056-45-7, name is Methyl 4-amino-1H-pyrazole-3-carboxylate, molecular formula is C5H7N3O2, 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.

A solution of 4-amino-1 H-pyrazole-3-carboxylic acid methyl ester (0.634 Kg, 4.49 mol, 1 wt) in 1 ,4-dioxane (8.90 L, 9 vol) under nitrogen was treated with triethylamine (0.761 L, 5.46 mol, 1.2 vol) followed by 2,6-dichlorobenzoyl chloride (0.710 L, 4.96 mol, 0.72 vol) such that the internal temperature was maintained in the range 20 to 25 0C. Residual 2,6- dichlorobenzoyl chloride was washed in with a line rinse of 1 ,4-dioxane (0.990 L, 1 vol) and the reaction mixture stirred at 18 to 25 C until complete (16 hours) by TLC analysis (eluent: ethyl acetate: heptanes 3:1 ; Rf amin80.25, Rf product 0.65). The reaction mixture was filtered, the filter-cake washed with 1 ,4-dioxane (2x 0.990 L, 2x 1 vol) and the combined filtrates (red) progressed to Stage 4 without further isolation.Triethylamine (1.42L, 10.20 MoI, 1.2 vol) was added to solution of 4-amino-1H-pyrazole-3- carboxylic acid methyl ester (1.184Kg, 8.39 MoI, 1.0 wt) in 1,4-dioxane (10.66L, 9.0 vol) at 15 to 25C under nitrogen. 2,6-Dichlorobenzoyl chloride (1.33L, 9.28 MoI, 1.12 vol) was charged at 15 to 250C followed by a line rinse of 1 ,4-dioxane (1.18L, 1.0 vol) and the reaction mixture stirred at 15 to 25C for 14 to 24 hours. Reaction completion was determined by 1H NMR analysis2. The reaction mixture was filtered, the filter-cake washed with 1 ,4-dioxane (2x 1.18L, 2x 1.0 vol) and the combined filtrates progressed to Stage 4 without further isolation.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 4-amino-1H-pyrazole-3-carboxylate, its application will become more common.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/1101; (2008); A2;,
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 934758-92-6 as follows. Product Details of 934758-92-6

Fuming nitric acid (14.00 ml, 329 mmol) was added at 0 ‘C over a period of 10 min to a solution of 5-chloro-1 H-pyrazole (10.0 g, 97.5 mmol) in acetic acid (14.0 ml, 245 mmol). The resulting mixture was stirred at 0 ‘C for 2 h, then acetic anhydride (33.0 ml, 349 mmol) was added and the reaction mixture was stirred at rt. Progress of the reaction was monitored by TLC and LCMS and when starting material was deemed completely consumed (after 4h), the reaction mixture was poured into ice-water (70 mL) and basified with Na2C03 (60 g) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with aqueous saturated sodium bicarbonate (100 mL) and brine (50 mL), dried over Na2S04 and concentrated. The afforded solid was washed with n-pentane which gave the title compound (7.0 g, 6.2%) as a solid. MS (ES+) 147.93 [M+H]+.

According to the analysis of related databases, 934758-92-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MEDIVIR AB; ALBERTELLA, Mark; OeBERG, Fredrik; (96 pag.)WO2018/141749; (2018); 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. 1280210-79-8, name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: 1280210-79-8

under nitrogen protection, Intermediate 2(604 mg, 2.87mmol) is dissolved in tetrahydrofuran (20 ml) in, lowering the temperature to 0 C, adding sodium hydride to (180 mg, 60 wt %, 4.5mmol), stirring 30 minutes. Then cyclopropyl sulfonyl chloride (1.27g, 9.0mmol), natural temperature to react at room temperature for 1 hour. Adding water to the reaction solution (20 ml) in the quenching of the reaction, ethyl acetate (20mL × 2) extraction, the combined organic layer, drying with anhydrous sodium sulfate, concentrated, re-dissolved in 5 ml of tetrahydrofuran, cooled to -10 C to 0 C, adding 3rd butanol potassium (36 mg, 0.32mmol), this temperature is kept under reaction 28 hours. The end of the reaction, adding citric acid aqueous solution (1 ml, 15%), the addition of water (10 ml), ethyl acetate (20mL × 3) extraction, the combined organic layer, drying with anhydrous sodium sulfate, concentrated. Silica gel column chromatography separation and purification of the residue (petroleum ether/ethyl acetate (v/v)=2:1), to obtain white solid1a (660 mg, yield 73%).

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; SICHUAN HAISCO PHARMACEUTICAL CO., LTD; ZHANG, CHEN; FAN, JIANG; LI, CAI-HU; WEI, YONG-GANG; (99 pag.)TW2017/8222; (2017); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics