Day: July 6, 2021

Synthetic Route of 288-13-1, 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 288-13-1 as follows.

General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999% purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98% purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.

According to the analysis of related databases, 288-13-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Teo, Yong-Chua; Yong, Fui-Fong; Lim, Gina Shiyun; Tetrahedron Letters; vol. 52; 52; (2011); p. 7171 – 7174;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route 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.

Step 1: A clean and dry 500 L glass-lined reactor A was evacuated to -0.08–0.O5MPa and filled with nitrogen to normal pressure. It was repeated for 3 times. The reactors were sampled for oxygen content to ensure it was 3%.[001145j Diisopropylamine (106.0 kg) and 1-methyl-4-iodo-1H-pyrazole (24.3 kg, 23.6 kg corrected) were added to the reactor A at 15-25 C. Cuprous iodide (0.37 kg) was added to reactor A under the protection of nitrogen at 15-25 C. Bis(triphenylphosphine)palladium(II) chloride (1.09 kg) was added to the mixture under the protection of nitrogen at 15-25 C. The mixture was stirred for 20-30 mi Trimethylsilylacetylene (22.2 kg, 14.0 kg corrected) was added to the mixture in portions with 4-5 kg and an interval of 20-30 mm for each portion at 15-30 C. The mixture was allowed to react at 20-30 C. After 2h, the mixture was sampled every 1-2h for purity analysis by HPLC until area% of 1-methyl-4-iodo-1H-pyrazole was 0.5%.[001 146j After reaction completion, the mixture was filtered with a stainless steel centrifuge. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). The filtrate was transferred to reactor A and concentrated under reduced pressure (P -0.08 MPa) at T 45 C until 40-60 L was left. Methyl tert-butyl ether (92.5 kg) was added to the mixture and concentration was continued until 40-60 L was left. Methyl tert-butyl ether (92.2 kg) was added to concentrated mixture and the mixture was sampled for diisopropylamine residual analysis to ensure it was 1%. Active carbon (4.9 kg) was added to the mixture at 15-25 C and the mixture was maintained for 6-8 h under stirring. The mixture was filtered with stainless steel nutsche filter at 15-25 C. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). A solution of citric acid monohydrate (6.1 kg) in purified water (121.6 kg) was added to the filtrate at 15-25 C. The mixture was stirred for 20-30 mm and settled for 20-3 0 mm before separation. The emulsion layer was separated to aqueous phase. The aqueous phase was sampled for pH analysis and wt% analysis to ensure pH was < 7. Active carbon (4.9 kg) was added to the mixture at 15-25 C and the mixture was maintained for 6-8 h under stirring. The mixture was filtered with stainless steel nutsche filter at 15-25 C. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). The filtrate was checked to ensure it was yellow solution. The filtrate was transferred to reactor B and concentrated under reduced pressure (P -0.O8MPa) at T 35 C until 30-40 L was left. Anhydrous ethanol (96.3 kg) was added to the mixture and concentration was continued at T 45 C until 30-40 L was left. The mixture was sampled for methyl tert-butyl ether residual analysis to ensure it was 0.5%. The mixture was cooled to 15-25 C. Purified water (121.3 kg) was added to the mixture through peristaltic pump at 15-25 C at a reference rate of 25-50 kg/h. Brown yellow solid precipitated. The mixture was allowed to crystallize at 15-25 C. After 2h, the mixture was sampled every 1- 2h for mother liquor wt% analysis until it was 0.5% or the difference between the two samples was 0.3%. The mixture was filtered with a stainless steel nutsche filter. The filter cake was rinsed twice with purified water (12.1 kg x2). The filter cake was swept in the stainless steel nutsche filter. After 12h, the solid was sampled every 6-8h for ethanol residual until it was 1%. The product was packaged in one plastic bag. Product weight12.0 kg, Yield = 52.3%, Purity (HPLC) = 98.9%. 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:
Patent; INFINITY PHARMACEUTICALS, INC.; CRENIER, Louis; LESCARBEAU, Andre; SHARMA, Praveen; GENOV, Daniel G.; (324 pag.)WO2017/48702; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 175137-46-9,Some common heterocyclic compound, 175137-46-9, name is 5-Cyclopropyl-1H-pyrazol-3-amine, molecular formula is C6H9N3, 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.

2,4-dichloropyrimidine 2 (13.30 g, 89.31 mmol) and 3-amino-5-cyclopropylpyrazole 1 (11.00 g, 89.31 mmol) were dissolved in tetrahydrofuran (TFA) (100 ml) followed by theaddition of deionized water (100 ml). The solution was then treated with potassium acetate (261.9 g, 2.5 mol). The resulting mixture was kept at 55C for 48 h. The mixture was filtered to remove excess potassium acetate. The organic layer was separated and dried using magnesium sulfate and concentrated before loading on an AnaLogix silica column. Intermediate 3 was separated as previously reported (34). ?H NMR (400 MHz, DMSO) oe 12.14 (s, 1H), 10.23 (s,1H), 1.84 (m, 1H), 0.88 (m, 2H), 0.64 (m, 2H). ?3C NMR (100 MHz, DMSO) oe 161.4, 160.7,160.0, 153.9, 148.6, 147.8, 146.8, 8.4, 8.2. MS calculated for C,0H,0N5 235.06, found 236.15 (M).

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

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; SHOKAT, Kevan, M.; MENDEZ, Aaron, S.; (131 pag.)WO2016/22839; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 118430-74-3, 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. 118430-74-3 name is 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, 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.

Intermediate I12.2, (0.20 g), 3-cyclopropyl-1-methyl-1H-pyrazole-5-amine (0.14 g), potassium t-butoxide (0.10 ml of a 1M THF solution) and dioxane (2 ml) were transferred to a microwave vial and heated under microwave irradiation under the following conditions: max power 150 W, T 150 C., 15 min; after the first cycle 0.05 mL of base were added and two more cycles of irradiation performed under the same conditions. The reaction mixture was evaporated to dryness, and the oily residue was purified by preparative LC-MS affording example 208 (as TFA salt) (0.09 g). HPLC (Rt)=7.12 min (method P)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2010/261687; (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. 948570-75-0, name is 1-(2-Methoxyethyl)-4-nitro-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H9N3O3

To a solution of l-(2-methoxyethyl)-4- nitro-pyrazole (3.0 g, 17.53 mmol) in MeOH (50 ml) was added 10 % Pd/C (300 mg) under N2. The suspension was degassed and purged with H2 several times. The mixture was stirred under a H2 atmosphere at 25 C for 3 h. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give the title compound as a red oil (Y = 97 %). NMR (400 MHz, chloroform-rf) d ppm 7.16 (s, 1H), 7.09 (s, 1H), 4.16 (t, J= 5 Hz, 2H), 3.69 (t, J= 5 Hz, 2H), 3.32 (s, 3H), 2.93 – 2.83 (hr. s, 2H).

According to the analysis of related databases, 948570-75-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NODTHERA LIMITED; HARRISON, David; WATT, Alan Paul; BOCK, Mark G.; (334 pag.)WO2019/121691; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 31037-02-2, 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. 31037-02-2, name is Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

5-Amino-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (5.0 g, 29.6 mmol) was added portionwise to a mixture of tert-butyl nitrite (4.57 g, 44.3 mmol) and copper (II) bromide (7.92 g, 35.5 mmol) in acetonitrile (20 mL). The mixture was heated to 60C for 2 h. The resulting mixture was poured into 6M HCl (200 mL) and extracted with dichloromethane (3 x 250 mL). The combined organics was dried on magnesium sulfate and concentrated in vacuo. The crude material was purified by column chromatography (SiO2, 0% to 50% ethyl acetate in hexanes) to afford 5-bromo-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester as an off-white solid (4.7 g, 68%). 1H NMR (CDCl3) : 7.93 (s, 1H), 4.32 (q, J = 7.2 Hz, 2H), 3.92 (s, 3H), 1.36 (t, J = 7.0 Hz, 3H).

The chemical industry reduces the impact on the environment during synthesis Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BOLIN, David Robert; DE VICENTE FIDALGO, Javier; HERMANN, Johannes Cornelius; TIVITMAHAISOON, Parcharee; YI, Lin; ZAK, Mark; WO2013/189904; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 50877-42-4, 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. 50877-42-4, name is 1-Benzyl-4-iodo-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 1-benzyl-4-iodo-1H-pyrazole (1.05 g, 3.70 mmol) , bis (pinacolato) diboron (1.00 g, 3.94 mmol) , potassium acetate (1.00 g, 9.88 mmol) and Pd (dppf) Cl2(130 mg, 0.18 mmol) in DMSO (20 mL) was stirred at 80 under N2for 7 h. The reaction mixture was cooled to rt and quenched with water (50 mL) . The resulting mixture was extracted with EtOAc (50 mL × 3) . The combined organic layers were washed with saturated aqueous NaCl (50 mL × 2) , dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 5/1 to give a light yellow oily product (200 mg, 19.0) .[1088]MS (ESI, pos. ion) m/z: 282.3 [M+1]+ and[1089]1H NMR (600 MHz, CDCl3) : delta (ppm) 7.84 (s, 1H) , 7.69 (s, 1H) , 7.34 (m, 3H) , 7.25 (m, 2H) , 5.32 (s, 2H) , 1.32 (s, 12H)

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, 1-Benzyl-4-iodo-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; LIU, Bing; ZHANG, Yingjun; CHENG, Changchung; HUANG, Jiuzhong; BAI, Shun; REN, Xingye; LI, Zhi; ZHOU, Youbai; (368 pag.)WO2016/615; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 10250-64-3, These common heterocyclic compound, 10250-64-3, name is 1-Methyl-3-phenyl-1H-pyrazole-5-carboxylic acid, 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: To a solution of 19 (1.2 eq) and HOBt(1.4 eq) in DMF (0.5 M) were added EDCI (1.3 eq) and a solution of 15a-j or 16a-j (1.0 eq) in DMF (0.25 M), Et3N (3.5 eq) at 0 C. The reaction mixture was stirred at room temperature for 24 hours, then diluted in AcOEt. The organic phase was washed with water twice, saturated aqueous NaHCO3 three times, and brine, then dried over Na2SO4,filtered, and concentrated. The residue was purified by flash column chromatography to give intermediates 17a-j and 18a-j.

The synthetic route of 10250-64-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 25; 23; (2015); p. 5619 – 5624;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 17635-44-8, These common heterocyclic compound, 17635-44-8, name is 3,4,5-Tribromopyrazole, 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 D183 (0.95 g, 8.3 mmol) in THF (50mL) was added 3,4,5-tribromo-1 H- pyrazole (2.8 g, 9.1 mmol), PPh3 (4.3 g, 16.6 mmol) and DEAD (3.6 g, 20.7mmol) at 0-5 C under N2. The reaction solution was stirred at rt for 16 hrs. The reaction solution was poured into water (50 mL) and extracted with EtOAc (100 ml_x2). The combined organic layer was washed with brine, dried over anhydrous Na2S04and concentrated in vacuo. The crude product was purified by gel silica column chromatography (PE:EtOAc from 50:1 to 10:1 ) to afford the title compound as yellow oilsolid (2.4g, yield 71.6 %). LC-MS 403.0 (M+H)+.

The synthetic route of 17635-44-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; DING, Xiao; HO, Ming-Hsun; REN, Feng; YU, Haihua; ZHAN, Yang; (290 pag.)WO2019/12093; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 20154-03-4, 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 20154-03-4 as follows.

To a stirred solution of 10 g (73.5 mmol) 3-(trifluoromethyl)-1H-pyrazole (3) in DMSO (150 ml) were added 9.9 g of potassium tert.-butoxide portion wise. After stirring for 5 minutes drop wise addition of 12 ml of iodoethane followed by stirring overnight were conducted. Water was added afterwards and the pH value was adjusted to 3 by using 1N HCl. The mixture was diluted with MTBE and extracted two more times with MTBE. The combined organic phase was washed with Na2S2O3-solution, water and brine yielding 8 g (67 percent) of the ionic liquid 8.

According to the analysis of related databases, 20154-03-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SOLVAY SA; Braun, Max Josef; Fischer, Reiner; EP2662359; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics