Day: June 21, 2021

Reference of 25016-11-9, 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. 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows.

Example 12: l-{l-[9-Methyl-8-(l-methyl-lH-pyrazol-4-yI)-9H-purin-6-yI]piperidin-4- yI}-l,3-dihydro-2H-benzimidazol-2-one (Compound 149)l H9-Methy -8-a-methyl-lH-pyrazol-^2H-benzimidazol-2-one[00207] To a solution of l-(l-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)- lH-benzo[d]imidazol-2(3H)-one (70 mg, 0.2 mmol) in anhydrous ethanol (8 mL) were added 1 -methyl- lH-pyrazole-4-carbaldehyde (34 mg, 0.3 mmol) and catalytic amount of hydrochloric acid (0.05 mL, 4M HCl in Dioxane, Aldrich). The reaction mixture was heated to 80 C for 18 hours. The resulting precipitate was collected by vacuum filtration, washed with ethanol (2 mL) and dried under reduced pressure, to give 62.6 mg (70% yield) of the title compound. NMR (400MHz, DMSO-d6): delta 10.84 (s, 1H), 8.41 (s, 1H), 8.25 (s, 1H), 8.02 (s, 1H), 7.13 (dd, 1H), 6.93 (m, 3H), 4.53 (m, 1H), 3.92 (s, 3H), 3.81 (d, 3H), 3.33 (m, 2H), 3.24 (m, 2H), 2.33 (m, 2H), 1.82 (d, 2H); MS (EI) for C22H23N9O: 430.4 (MH+).

The chemical industry reduces the impact on the environment during synthesis 1-Methyl-1H-pyrazole-4-carbaldehyde. I believe this compound will play a more active role in future production and life.

Reference:
Patent; EXELIXIS, INC.; PATRICK, Kearney; WO2012/37226; (2012); 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. 37687-24-4, name is Diethyl 3,5-pyrazoledicarboxylate, This compound has unique chemical properties. The synthetic route is as follows., Safety of Diethyl 3,5-pyrazoledicarboxylate

Example 4: ethyl 4-hydroxy-6-methyl-pyrazolo[l,5-a]pyrazine-2-carboxylate (0257) l-Chloropropan-2-one (10.5 kg, 113 mol) was added slowly at room temperature (0258) (exothermic) to a suspension of diethyl lH-pyrazole-3,5-dicarboxylate (20 kg, 94.2 mol) and cesium carbonate (30.7 kg, 94.2 mol) in acetone (200 1). The reaction mixture was stirred for 1.5 hours, filtred and the precipitate was washed with acetone. Acetone was distilled off from the filtrate at 60 C to obain a volume of 60-90 1, DMSO (85 1) was added and the distillation was continued until acetone was completely removed. (0259) Ammonium acetate (14.5 kg, 188 mol) was added at room temperature. The reaction mixture was stirred at 80 C for 18 hours, cooled to 60 C and water (290 1) was slowly added. The suspension was stirred 2 hours at 0-5 C. The precipitate was filtered off, washed with water and dried at 70 C under high vacuum affording ethyl 4-hydroxy-6- methyl-pyrazolo[l,5-a]pyrazine-2-carboxylate (16.8 kg, 80.6%) as beige crystals. (0260) 1H-NMR (600 MHz, DMSO-d6): 11.51 (s, 1H), 7.62 (s, 1H), 7.32 (s, 1H), 4.33 (q, 2H), 2.14 (s, 3H), 1.32 (t, 3H); MS(ISP): m/e = 222.09 (M+H+).

According to the analysis of related databases, 37687-24-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DOTT, Pascal; FEYEN, Fabian; HILDBRAND, Stefan; HOFFMANN, Ursula; HOFFMANN-EMERY, Fabienne; MEIER, Roland; MOINE, Gerard; REGE, Pankaj; WUITSCHIK, Georg; (64 pag.)WO2017/186668; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 25016-20-0, A common heterocyclic compound, 25016-20-0, name is 1-Methyl-1H-pyrazole-3-carboxylic acid, molecular formula is C5H6N2O2, 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.

i-Methyl-I H-pyrazole-3-carboxylic acid (48.8 mg) was dissolved in a solution of DMF (3 ml_), DIPEA (182 mul_) and HATU (201 mg), the reaction was stirred at room temperature for 15 mins. Intermediate 64 (150 mg) in DMF (1 ml.) was added and the reactions were stirred at 5O0C under nitrogen for 22 h. The reaction mixture was evaporated in vacuo and was partitioned between DCM and saturated sodium bicarbonate solution. The organic phase was collected and dried by passing through a hydrophobic frit and evaporated in vacuo. The crude material was purified using a 12 g silica ISCO cartridge eluting with a gradient of 5 – 100% EtOAc in cyclohexane to give the title compound. MS calcd for (C29H34N4O4S + H)+ : 535 MS found (electrospray) : (M+H)+ = 535

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; SMITHKLINE BEECHAM CORPORATION; WO2008/59042; (2008); 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. 694-31-5, name is 1,5-Dimethyl-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 1,5-Dimethyl-1H-pyrazole

General procedure: To a solution of pyrazole 1a (50.0 g, 0.45 mol) in pyridine (200 mL,2.6 mol) cooled to 0 C (CF3CO)2O (69.5 mL, 0.50 mol) was added dropwise. The mixture was stirred at r.t. for 12 h. H2O (1000 mL) was added. The formed suspension was washed with CH2Cl2 (3 × 500 mL). The organic layer was dried (Na2SO4), filtered, and evaporated under vacuum. The residue was purified by vacuum distillation (bp 107-110 C/26.7 mbar) to afford pure 2a (78.6 g, 0.38 mmol, 84%) as a yellowish liquid.

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 694-31-5.

Reference:
Article; Yarmoliuk, Dmytro V.; Arkhipov, Viatcheslav V.; Stambirskyi, Maksym V.; Dmytriv, Yurii V.; Shishkin, Oleg V.; Tolmachev, Andrei A.; Mykhailiuk, Pavel K.; Synthesis; vol. 46; 9; (2014); p. 1254 – 1260;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, 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. Safety of 3-Methyl-4-nitro-1H-pyrazole

DIAD (930 muIota_, 4.7 mmol) was added to a solution of 3-methyl-4-nitro-1 H-pyrazole (500 mg, 3.93 mmol), /V-methyl-4-piperidinol (453 mg, 3.93 mmol) and triphenylphosphine (1238 mg, 4.7 mmol) in THF (25ml_). The reaction mixture was stirred at rt for 5 days. The mixture was cone, in vacuo before purification by flash chromatography on silica, washing with 50% EtOAc/DCM, followed by 5/45/50 MeOH/EtOAc/DCM mixture. The product was eluted with 2/5/43/50 NEt3/MeOH/EtOAc/DCM mixture to give the title compound as an off-white low melting solid (202 mg, 23%). LCMS (Method 1 ) Rt 2.7 min, ESIMS m/z [M+H]+ 225.3.

The synthetic route of 5334-39-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIONOMICS LIMITED; HARVEY, Andrew John; RIPPER, Justin Anthony; HUFF, Belinda Cheryl; PAUL, Dharam; WO2015/123722; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3528-45-8,Some common heterocyclic compound, 3528-45-8, name is 1-(4-Methoxybenzyl)-1H-pyrazol-5-amine, molecular formula is C11H13N3O, 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.

1-(4-Methoxybenzyl)-1H-pyrazol-5-amine (3.94 g, 1 9.39 mmol), followed by diethyl 2-(ethoxymethylene)malonate (4 mL, 20 mmol) was added to a 200 mL round bottom flask fitted with a distillation head to remove ethanol. The mixture was heated to 130 C for 45 min, then 10 mL of diphenyl ether was added and the temperature was raised to 240 C for 2 h. The reaction mixture was then cooled to rt and Et2O ( 1 00 mL) was added. The resulting precipitate was collected by vacuum filtration and dried under vacuum to afford the target compound as a white solid (4 g, 62%).

The synthetic route of 3528-45-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GENENTECH,INC.; FORMA TM, LLC; BAIR, Kenneth W.; BAUMEISTER, Timm R.; BUCKMELTER, Alexandre J.; CLODFELTER, Kanl H.; DRAGOVICH, Peter; HAN, Bingsong; LIN, Jian; LIU, Xiongcai; REYNOLDS, Dominic J.; SMITH, Chase C.; WANG, Zhongguo; YUEN, Po-Wai; ZAK, Mark; ZHANG, Yamin; ZHENG, Xiaozhang; ZHAO, Guiling; WO2013/127268; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 5203-77-0, A common heterocyclic compound, 5203-77-0, name is 1,3-Dimethyl-1H-pyrazol-5-ol, molecular formula is C5H8N2O, 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: Intermediate 7 (4mmol), dissolved in dry dichloromethane (60mL), and PCl5 (4.2mmol) were added and stirred at room temperature for 1h. The solvent was moved out under reduced pressure to afford acid chloride, the acid chloride was then dissolved in dry CH2Cl2 (60mL), Then 1-methyl-1H-pyrazol-5-ol (4mmol) and Et3N (4.8mmol) were added to the above solution, and stirred for a further 18-24hat room temperature. After adding dichloromethane (30mL), the resultant mixture was washed sequentially with 2N hydrochloric acid (100mL), saturated NaHCO3 and saturated NaCl and dried over Na2SO4. The rest of the solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V:V = 1:2) to obtain the desired intermediate 8 as a write powder (30%-70%). 4.1.10 1-methyl-1H-pyrazol-5-yl3-methyl-2-oxo-1-propyl-2,3-dihydro-1H-benzo[d] imidazole- 5-carboxylate Yield: 45%. m.p. 107-108C. 1H NMR (600MHz, CDCl3) delta 8.01 (dd, J=8.4, 1.2Hz, 1H), 7.77 (d, J=1.2Hz, 1H), 7.48 (d, J=1.8Hz, 1H), 7.10 (d, J=8.4Hz, 1H), 6.20 (d, J=1.8Hz, 1H), 3.92 (t, J=7.2Hz, 2H), 3.80 (s, 3H), 3.51 (s, 3H), 1.91-1.71 (m, 2H), 1.00 (t, J=7.8Hz, 3H). EI-MS (m/z): 314.18 (M)+.

The synthetic route of 5203-77-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xu, Yu-Ling; Lin, Hong-Yan; Ruan, Xu; Yang, Sheng-Gang; Hao, Ge-Fei; Yang, Wen-Chao; Yang, Guang-Fu; European Journal of Medicinal Chemistry; vol. 92; (2015); p. 427 – 438;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 35277-02-2,Some common heterocyclic compound, 35277-02-2, name is 4-Fluoro-1H-pyrazole, molecular formula is C3H3FN2, 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 C72 (222 mg, 0.539 mmol) in N,N-dimethylformamide (3 mL) were added cesium carbonate (528 mg, 1.62 mmol) and 4-fluoro-1H-pyrazole (69.6 mg, 0.809 mmol). The reaction mixture was stirred overnight at room temperature, and then at 50 C. for 3 hours, whereupon it was diluted with water and extracted with ethyl acetate (3*50 mL). The combined organic layers were dried over magnesium sulfate, filtered, concentrated in vacuo, and purified via chromatography on silica gel (Gradient: 10% to 65% ethyl acetate in heptane) to provide the product as a colorless oil. Yield: 148 mg, 0.455 mmol, 84%. LCMS m/z 326.4 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 7.37 (d, J=5.1 Hz, 1H), 7.32 (d, J=4.3 Hz, 1H), 4.88-4.80 (m, 1H), 4.15 (dd, half of ABX pattern, J=10.0, 6.0 Hz, 1H), 4.10 (dd, half of ABX pattern, J=10.2, 4.7 Hz, 1H), 3.68-3.56 (br m, 2H), 3.37-3.26 (m, 2H), 2.28 (dd, half of ABX pattern, J=13.7, 8.6 Hz, 1H), 2.17 (dd, half of ABX pattern, J=13.5, 5.3 Hz, 1H), 1.80-1.59 (m, 3H), 1.59-1.49 (m, 1H), 1.44 (s, 9H).

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

Reference:
Patent; PFIZER INC.; BRODNEY, MICHAEL AARON; BUTLER, CHRISTOPHER RYAN; MCALLISTER, LAURA ANN; HELAL, CHRISTOPHER JOHN; O’NEIL, STEVEN VICTOR; VERHOEST, PATRICK ROBERT; (103 pag.)US2018/208607; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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

[0553] To a solution of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (83 mg, 0.3mmol) in HOAc (2 mL) was added sodium 2-nitro-1,3-dioxopropan-2-ide (47 mg, 0.3 mmol).After stirring at RT for 1 hr, water (2 mL) was added. The mixture was partitioned between EA(25 mL) and brine (25 mL). The combined organic layers were washed with brine (25 mL x 2),dried over Na2S04 and concentrated to afford 90 mg of 6-nitro-2-(4-phenoxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (84percent) as a yellow solid. MS (ESI) m/e[M+1t 358.2.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; GUO, Yunhang; BEIGENE, LTD.; WANG, Zhiwei; WO2014/173289; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 83725-05-7, 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 83725-05-7 as follows.

A mixture of N-(5-methyl-1H-pyrazol-3-yl)acetamide (1.448 g, 10.4 mmol),1 3,4-dihydro-2H-pyran (2.39 mL, 26.0 mmol) and trifluoroacetic acid (15 muL, 0.208 mmol) in anhydrous MeCN (15 mL) was refluxed for 2 h. Solvent was evaporated and the residue was resuspended in CH2Cl2 (50 mL) and washed with H2O and brine. After drying with Na2SO4, solvent evaporation and silica gel column chromatography (PE-EtOAc, 6:4) N-(5-Methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)acetamide (1.87 g, quantitative) was obtained. 1Lu, Y.; Kraatz, H.-B. Inorg. Chim. Acta 2004, 357, 159-1661H NMR (400 MHz, CDCl3): =7.61 (bs, 1H), 6.50 (s, 1H), 5.15 (dd, J=10.0 Hz, J=2.4 Hz, 1H), 4.05 (d, J=11.4 Hz, 1H), 3.63 (dt, J=11.8 Hz, J=2.5 Hz, 1H), 2.31 (s, 3H), 2.30 (m, 1H), 2.09 (s, 3H), 2.06 (m, 1H), 1.86 (d, J=11.0 Hz, 1H), 1.63-1.67 (m, 3H).MS (ESI): m/z=224.37 [MH+].

According to the analysis of related databases, 83725-05-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AC IMMUNE SA; US2010/144793; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics