Category: pyrazoles-derivatives

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. COA of Formula: C4H7N3

3rd generation BrettPhos pre-catalyst (0.227 g, 0.25 mmol) was added to methyl i-(i((tert-butoxycarbonyl)amino)-3 -methoxypropan-2-yl)-4-(2-chloro-5 -methylpyrimidin-4- yl)-1H-pyrrole-2-carboxylate (1.1 g, 2.51 mmol), i-methyl-1H-pyrazol-5-amine (0.487 g, 5.01 mmol) and cesium carbonate (2.041 g, 6.27 mmol) in 1,4-dioxane (30 mL) at 25 °C under nitrogen. The resulting solution was stirred at 85 °C for 3 hours. The reactionmixture was poured into water (25 mL), extracted with EtOAc (3 x 50 mL), the organic layer was dried over Na2SO4, filtered and evaporated to afford crude yellow solid. The crude product was purified by flash silica chromatography, elution gradient 80 to 90percent EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford methyl 1 -(1- ((tert-butoxycarbonyl)amino)-3 -methoxypropan-2-yl)-4-(5 -methyl-2-(( i-methyl-i H25 pyrazol-5-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylate (0.700 g, 55.9 percent) as a whitefoam. mlz: ES+ [M+H]+ 500.

The synthetic route of 1192-21-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WARD, Richard, Andrew; GRAHAM, Mark, Andrew; SWALLOW, Steven; JONES, Clifford, David; (282 pag.)WO2016/162325; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 330792-70-6, These common heterocyclic compound, 330792-70-6, name is 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile, 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.

5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (1.5 g, 5.4 mmol)And a mixture of K2CO3 (2.24 g, 16.3 mmol) in DMF (50 mL),Stir for 45 minutes under nitrogen at 80C.Then, tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (4.5 g, 16.3 mmol) was added in one portion.The reaction mixture was stirred at 80 C for 1 h.It was then cooled to room temperature and water (150 mL) and EA (150 mL) were added.The aqueous phase was further extracted with EA (100 mL x 3) and the combined organic phases were washed with saturated brine, dried over Na2SO4, concentrated, and purified on a tannin extract column (15 g of silica gel, DCM/MeOH = 400/1 to 200/1).An off-white solid product 3-cyano-2-(4-phenoxyphenyl)-5,6-dihydro-4H-pyrazolo[5′,1′:2,3]imidazo[4, 5-c]tert-Butyl pyridine-7(8H)-carboxylate (850 mg, 35%).

Statistics shows that 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile is playing an increasingly important role. we look forward to future research findings about 330792-70-6.

Reference:
Patent; BEIGENE, LTD; WANG, ZHIWEI; GUO, YUNHANG; (300 pag.)TWI602818; (2017); B;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 1780-72-9, These common heterocyclic compound, 1780-72-9, name is 4-Bromo-5-methyl-1H-pyrazol-3-amine, 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.

General procedure: The kinetics of reactions were followed by measuring the change in absorbance at suitable wavelengthsas a function of time. Working wavelengths were determined for each reaction system, recording thespectra of reaction mixture over wavelength range between 220 and 600 nm. Substitution reactionswere studied under pseudo-first-order conditions whereas the concentration of entering ligand wasalways in large excess (at least 10-fold). Reactions were initiated by mixing equal volumes (1.5 cm3) ofcomplex (2 × 10-4 M) and ligand (2 × 10-3; 4 × 10-3; 6 × 10-3; 8 × 10-3; 1 × 10-2 M) solutions in a quartzcuvette. The changes in absorbance versus time were fitted as a single-exponential function usingOrigin Pro 8. Values for the pseudo-first-order rate constants, kobsd, were calculated as the average valuefrom three to five independent kinetic runs. Experimental data are reported in tables S2-S13 (supplementarymaterial). The values of pseudo-first-order rate constants, kobsd, at 298 K were recalculatedby Guggenheim and Kezdy-Swinbourne methods (table 14S) [33, 34]. All reactions were studied atfour different temperatures (288, 298, 308, and 313 K). The activation parameters, DeltaH? and DeltaS?, werecalculated using the Eyring equation. Eyring plots for all studied systems are given in supplementarymaterial, figures 4S-15S.

Statistics shows that 4-Bromo-5-methyl-1H-pyrazol-3-amine is playing an increasingly important role. we look forward to future research findings about 1780-72-9.

Reference:
Article; Kosovi?, Milica; Jovanovi?, Sne?ana; Bogdanovi?, Goran A.; Giester, Gerald; Ja?imovi?, ?eljko; Bugar?i?, ?ivadin D.; Petrovi?, Biljana; Journal of Coordination Chemistry; vol. 69; 19; (2016); p. 2819 – 2831;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 612511-81-6,Some common heterocyclic compound, 612511-81-6, name is (1-Methyl-1H-pyrazol-3-yl)methanamine, molecular formula is C5H9N3, 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 methyl 4-fluoro-3-nitrobenzoate (350 mg, 1 .758 mmol) in DMF (5 mL) were added (1 – methyl-1 H-pyrazol-3-yl)methanamine (205 mg, 1 .845 mmol) and K2C03 (316 mg, 2.285 mmol), and the reaction mixture was stirred at room temperature overnight. The reaction was then quenched with water (10 mL), and the resulting solid was isolated by filtration, washed with water, and dried in vacuum oven for 4 hours to afford methyl 4-(((1 -methyl-1 H- pyrazol-3-yl)methyl)amino)-3-nitrobenzoate (395 mg) as a yellow solid. LC-MS (ES) m/z = 291 [M+H]+. NMR (400 MHz, DMSO-c/6): delta 3.81 (s, 3H), 3.83 (s, 3H), 4.59 (d, J = 5.8 Hz, 2H), 6.20 (d, J = 2.3 Hz, 1 H), 7.19 (d, J = 9.4 Hz, 1 H), 7.64 (d, J = 2.0 Hz, 1 H), 7.97 (dd, J = 9.0, 1 .9 Hz, 1 H), 8.64 (d, J = 2.0 Hz, 1 H), 8.96 (t, J = 5.6 Hz, 1 H).

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

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; MEDINA, Jesus Raul; TIAN, Xinrong; NG DI MARCO, Christina; GRAYBILL, Todd L.; HEERDING, Dirk A.; LI, William Hoi Hong; MANGATT, Biju; MARTYR, Cuthbert D.; RIVERO, Raphael Anthony; (570 pag.)WO2019/49061; (2019); 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. 155377-19-8, name is Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C7H7F3N2O2

Ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (95.00 g, 0.456 mol) was dissolved in dry THF (1 L) and the resulting solution cooled in an acetone/ice bath. A 1M solution of LiAlH4 in THF (550 mL, 0.550 mol) was added over 30 min, keeping the temperature <10 C. Cooling was then removed and the reaction mixture was stirred at RT for 4 h. The reaction was again cooled and a 1:1 THF:water solution (250 mL) was added with cooling (maintaining the temperature <20 C.), followed by 5M HCl (160 mL) to neutrality/pH 6. EtOAc (1.5 L) was added and the mixture stirred for 30 min then left to settle overnight. The resulting grey granular solid was removed by filtration through dicalite and washed with EtOAc. The combined filtrates were washed with brine and dried over MgSO4, before concentrating in vacuo to give a white solid (76.00 g, 0.457 mol, 100%).1H NMR (400 MHz, CD3OD): delta 4.61 (s, 2H), 7.75 (s, 1H). 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; N.V. Organon; US2009/131455; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 2458-26-6, name is 3-Phenyl-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 2458-26-6, name: 3-Phenyl-1H-pyrazole

Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yl)butanoate 3-Phenyl-1 H-pyrazole (250 mg, 1 .73 mmol), methyl crotonate (275 muIota, 2.60 mmol) and DBU (130 muIota, 0.87 mmol) were combined in acetonitrile (3.5 ml), under nitrogen. The reaction was stirred at 50 C for 18 h and by TLC the reaction was complete. All of the volatiles were removed in vacuo and the crude material was purified by column chromatography, eluting 15-25% ethyl acetate/petroleum spirits. The title compound was obtained as a colourless oil [32] mg, 76%). HPLC – rt 7.48 min > 98% purity at 254 nm; LRMS [M+H]+ 245.2 m/z; HRMS [M+H]+ 245.1285 m/z, found 245.1284 m/z; 1 H NMR (400 MHz, DMSO) delta 7.87 – 7.70 (m, 3H), 7.44 – 7.33 (m, 2H), 7.33 – 7.19 (m, 1 H), 6.66 (d, J = 2.3 Hz, 1 H), 4.93 – 4.62 (m, 1 H), 3.56 (s, 3H), 2.93 (ddd, J= 22.0, 16.0, 7.0 Hz, 2H), 1 .48 (d, J = 6.8 Hz, 3H); 13C NMR (101 MHz, DMSO) delta 170.8, 149.7, 133.5, 130.3, 128.6 (2C), 127.3, 125.0 (2C), 102.2, 54.0, 51 .5, 40.5, 20.9.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; MONASH UNIVERSITY; THE UNIVERSITY OF WESTERN AUSTRALIA; BAELL, Jonathan; PIGGOTT, Matthew; RUSSELL, Stephanie; TOYNTON, Arthur; RAHMANI, Raphael; FERRINS, Lori; NGUYEN, Nghi; (178 pag.)WO2015/172196; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 31037-02-2, name is Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate, molecular formula is C7H11N3O2, 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. Safety of Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate

Carboxylate 62 (20.0 g, 118 mmol) in ethanol (100 mL) was treated with aqueous sodium hydroxide (50 mL, 3 M). The reaction mixture was heated to reflux and allowed to stir for 2 h and the ethanol removed under reduced pressure. The aqueous solution was cooled to 0 C and acidified with HCl (3 M) to pH 5. The white precipitate was collected by filtration and heated neat to 185 C in Kugelrohr oven under vacuum (1 mmHg) to afford titled compound 22 (10.0 g, 87%) as a light brown solid. MP: 73 – 74 C; IR (Diamond Cell, neat): 3395, 3134, 1643, 1556, 1517, 1431, 1344, 1268, 1207, 999, 928, 758, 632 cm-1; 1H NMR (300 MHz, Chloroform-d) delta 7.21 (d, J = 2.0 Hz, 1H), 5.49 (d, J = 2.0 Hz, 1H), 3.62 (s, 3H), 3.50 (br. s, 2H); 13C NMR (75 MHz, Chloroform-d) delta 144.6 (C), 138.2 (CH), 91.2 (CH), 34.3 (CH3); LRMS (ESI+) m/z: 98 (100, [M + H]+), 120 (50, [M + Na]+). This data matched that previously reported. 3

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 31037-02-2, its application will become more common.

Reference:
Article; Katte, Timothy A.; Reekie, Tristan A.; Werry, Eryn L.; Jorgensen, William T.; Boyd, Rochelle; Wong, Erick C.N.; Gulliver, Damien W.; Connor, Mark; Kassiou, Michael; European Journal of Medicinal Chemistry; vol. 136; (2017); p. 330 – 333;,
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. 96799-02-9, name is 5-(Furan-2-yl)-1H-pyrazol-3-amine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 5-(Furan-2-yl)-1H-pyrazol-3-amine

Synthesis of 2-(5-Amino-3-furan-2-yl-pyrazol-1-yl)-1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethanone Protocol T was followed using 3-Furan-2-yl-2H-pyrazol-5-ylamine, K2CO3, 2-Chloro-1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethanone and DMF. Column chromatography using 100% ethyl acetate afforded the title compound as a white solid. 1H NMR (400 MHz, CD6CO) delta 7.48-7.52 (m, 1H), 6.98-7.06 (m, 2H), 6.52-6.56 (m, 2H), 6.44-6.48 (m, 2H), 5.74 (s, 1H), 4.98 (s, 2H), 3.68-3.88 (m, 4H), 3.12-3.24 (m, 4H). MS (ES) M+H) expected=369.4, found 370.1.

According to the analysis of related databases, 96799-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ChemoCentryx, Inc.; US2004/162282; (2004); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 16034-46-1,Some common heterocyclic compound, 16034-46-1, name is 1-Methyl-1H-pyrazole-5-carboxylic acid, molecular formula is C5H6N2O2, 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 tert-butyl {4-methyl-2-[3-(methylsulfonyl)benzyl]-1,3-thiazol-5-yl}carbamate (300 mg, 0.78 mmol) obtained in Example 233-F) in ethanol (2 mL) was added dropwise concentrated hydrochloric acid (0.600 mL) at room temperature, and the mixture was stirred at 50C for 1 hr. The reaction mixture was cooled to 0C, neutralized with 8N aqueous sodium hydroxide solution, adjusted to pH 10-11 with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in DMA (3 mL), and 1-methyl-1H-pyrazole-5-carboxylic acid (118 mg, 0.94 mmol), HATU (356 g, 0.94 mmol) and DIEA (0.068 mL, 0.39 mmol) were added at room temperature. The reaction mixture was stirred at 60C for 2 hr, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: hexane-ethyl acetate (1:4-0:1)] and basic silica gel column chromatography [eluent: hexane-ethyl acetate (1:9-0:1)], and crystallized from ethyl acetate-hexane to give the title compound (159 mg) as white crystals (yield 52%). MS (ESI+) : [M+H]+ 391. 1H NMR (300 MHz, DMSO-d6) delta 2.31 (3H, s), 3.31 (3H, s), 4.04 (3H, s), 4.37 (2H, s), 7.06 (1H, d, J = 1.9 Hz), 7.53 (1H, d, J = 1.9 Hz), 7.59-7.74 (2H, m), 7.80-7.87 (1H, m), 7.91 (1H, brs), 10.52 (1H, s).

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

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2530078; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 82231-58-1, 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. 82231-58-1, name is Ethyl 2-(4-bromo-1H-pyrazol-1-yl)acetate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 4,4,5,5-tetramethyl- 2-(4,4,5,5-tetramethyl (1,3.2 – dioxaborolan-2-yl)) -1,3,2-dioxaborolane (436mg, 1.72mmol) in DMF (1OmL) at O0C were added KOAc (420mg, 4.29mmol) and Pd(dppf)Cl2.CH2Cl2 (35mg, 0.043mmol). The reaction mixture was heated to 8O0C at which point a solution of 27b (333mg, 1.43mmol) in DMF (1OmL) was added drop-wise. The resulting mixture was stirred at 8O0C overnight and evaporated to dryness. The residue was chromatographed on silica gel (ethyl acetate/petrol=l : 10) to provide 27c (76mg, 19%).

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, Ethyl 2-(4-bromo-1H-pyrazol-1-yl)acetate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; XCOVERY, INC.; WO2008/88881; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics