Month: September 2021

Related Products of 25016-20-0, These common heterocyclic compound, 25016-20-0, name is 1-Methyl-1H-pyrazole-3-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.

Example 238 Production of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-fluorophenyl]-1-methyl-1H-pyrazole-3-carboxamide To a solution of 1-methyl-1H-pyrazole-3-carboxylic acid (115 mg, 0.92 mmol) in tetrahydrofuran (4.0 mL) were added N,N-dimethylformamide (20 muL, 0.26 mmol) and oxalyl chloride (80 muL, 0.92 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.62 mmol) in N,N-dimethylacetamide (4.0 mL), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure and ethanol (10 mL) was added to the residue. The mixture was stirred with heating at 75 C. and cooled to room temperature, and the precipitate was collected by filtration to give the title compound (144 mg, 54%) as a white powder. 1H-NMR (DMSO-d6, 300 MHz) delta 0.77-0.83 (4H, m), 1.87-1.97 (1H, m), 3.97 (3H, s), 6.77 (1H, d, J=2.4 Hz), 7.06-7.16 (2H, m), 7.36-7.43 (1H, m), 7.82-7.89 (2H, m), 7.95 (1H, s), 8.05 (1H, d, J=9.6 Hz), 9.59 (1H, s), 11.08 (1H, s).

Statistics shows that 1-Methyl-1H-pyrazole-3-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 25016-20-0.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; US2009/137595; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 632365-54-9, 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. 632365-54-9, name is Methyl 5-amino-1H-pyrazole-3-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

With stirring, a mixture of 10 g (0.037 mol) of dimethyl(2-chloro-4-cyanophenyl)malonate, 5.2 g (0.037 mol) of methyl 5-amino-1H-pyrazole-3-carboxylate and 7.6 g (0.041 mol) of tri-n-butyl-amine was heated at 180 C. for 6 hours. The methanol released during the reaction was continuously distilled off. The reaction mixture was then concentrated under reduced pressure. This gave 12.8 g (100% of theory) of methyl 5,7-dihydroxy-6-(2-chloro-4-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate. The product was used for further syntheses without additional purification.

The chemical industry reduces the impact on the environment during synthesis Methyl 5-amino-1H-pyrazole-3-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Gebauer, Olaf; Gayer, Herbert; Heinemann, Ulrich; Herrmann, Stefan; Hillebrand, Stefan; Elbe, Hans-Ludwig; Ebbert, Ronald; Wachendorff-Neumann, Ulrike; Dahmen, Peter; Kuck, Karl-Heinz; US2005/187224; (2005); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 930-36-9, These common heterocyclic compound, 930-36-9, name is 1-Methylpyrazole, 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.

Under room temperature, the 1-methyl -1H-pyrazole (2.0g, 24.4 mmol) dissolved in THF in (30 ml). Under the protection of the nitrogen of the obtained mixture to lower the temperature to -78 C, then slowly dripping n-BuLi to the (10.72 ml, 26.8 mmol). Then the resulting mixture at -78 C stirring 2 hours, to room temperature, then the stirring is performed for 1 hour. Then to the reaction solution to maintain this temperature in drying CO2gas, approximately through 5 minutes. After stirring at room temperature, to 1 hours. To the obtained water is added in the mixture of (30 ml) the reaction quenching and diluting. The resulting mixture is extracted with methylene chloride. After acid aqueous phase precipitating a large amount of solid, filtered. The resulting filter cake is dried to obtain 1.5 g of white solid (yield: 48.8%).

Statistics shows that 1-Methylpyrazole is playing an increasingly important role. we look forward to future research findings about 930-36-9.

Reference:
Patent; CSPC Weisheng Pharmaceutical Technology (Shijiahuang) Co., Ltd.; Shi, Ying; Gao, Qingzhi; Mi, Yi; Wang, Xuliang; (129 pag.)CN105384739; (2016); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3920-50-1,Some common heterocyclic compound, 3920-50-1, name is Pyrazole-3-carboxaldehyde, molecular formula is C4H4N2O, 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.

Reference Production Example 6-1 1-(hydroxymethyl)-3-formyl-1H-pyrazole The mixture of 0.96 g of 3-formyl-1H-pyrazole, 0. 60 g of paraformaldehyde and 0.3 ml of triethylamine was stirred at 100 °C for 5 hours. After the reaction mixture was cooled to room temperature, acetone was added to the reaction mixture. The mixture was filtered. The filterate was concentrated under reduced pressure to obtain 1.21 g of 1-(hydroxymethyl)-3-formyl-1H-pyrazole. The crude product was used for next process without purification. 1H-NMR(CDCl3,TMS,delta(ppm)):5.63(2H,s),6.84(1H,d),7.67(1H,d),9.96(1H,s)

The synthetic route of 3920-50-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sumitomo Chemical Company, Limited; EP1710234; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

14521-80-3, name is 3-Bromo-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. HPLC of Formula: C3H3BrN2

Step C: Preparation of 2-(3-Bromo-1H-pyrazol-1-yl)-3-chloropyridineTo a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-bromopyrazole (i.e. the product of Step B) (25.4 g, 176 mmol) in dry N,N-dimethylformamide (88 mL) was added potassium carbonate (48.6 g, 352 mmol), and the reaction mixture was heated to 125 C. for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 mL). A precipitate formed. The precipitated solids were stirred for 1.5 hrs, filtered and washed with water (2×100 mL). The solid filter cake was taken up in methylene chloride and washed sequentially with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution, and brine. The organic extracts were then dried over magnesium sulfate and concentrated to afford 39.9 g of a pink solid. The crude solid was suspended in hexane and stirred vigorously for 1 hr. The solids were filtered, washed with hexane and dried to afford the title product as an off-white powder (30.4 g) determined to be >94% pure by NMR. This material was used without further purification in Step D. 1H NMR (CDCl3) delta 6.52 (s, 1H), 7.30 (dd, 1H), 7.92 (d, 1H), 8.05 (s, 1H), 8.43 (d, 1H).

The synthetic route of 14521-80-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; E I DU PONT DE NEMOURS AND COMPANY; Lahm, George Philip; McCann, Stephen Frederick; Patel, Kanu Maganbhai; Selby, Thomas Paul; Stevenson, Thomas Martin; US9113630; (2015); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application 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.

Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then 1,3-dimethyl-1H-pyrazol-5-ol (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue 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 10.

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; Cao, Run-Jie; Ming, Ze-Zhong; Yang, Wen-Chao; Yang, Guang-Fu; Bioorganic and Medicinal Chemistry; vol. 22; 19; (2014); p. 5194 – 5211;,
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. 916211-79-5, name is 5-Chloro-1H-pyrazol-3-amine, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C3H4ClN3

A solution of ie/ -butyl 4-methyl-3-oxopentanoate (2.52 g, 13.6 mmol) in DMF-DMA (1.8 mL) was heated at 120 C for 1 hour. The solution was cooled to 80 C and a solution of 3- chloro-lH-pyrazol-5-amine (1.6 g, 13.6 mmol) in EtOH (21 mL) was added. The resulting mixture was stirred for 2 hours at 80 C. The solvent was removed in vacuo then concentrated under reduced pressure. The residue was purified by silica chromatography (petroleum ethenEtOAc = 40: 1) to give the title compound (2.1 g, 52% yield). 1H NMR (400 MHz, DMSO-Mu): delta 8.76 (s, 1H), 6.97 (s, 1H), 4.30 (m, 1H), 1.57 (s, 9H), 1.52 (d, = 7.2 Hz, 6H). MS m/z 296.45 [M+H]+.

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 916211-79-5.

Reference:
Patent; CORNELL UNIVERSITY; DANA-FARBER CANCER INSTITUTE, INC.; CHILDREN’S MEDICAL CENTER CORPORATION; MELNICK, Ari, M.; GABAS, Lorena, Fontan; US, Ilkay; CASALENA, Gabriella; GRAY, Nathanael, S.; SCOTT, David, A.; HATCHER, John; DU, Guangyan; WU, Hao; QIAO, Qi; (157 pag.)WO2018/85247; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 13808-64-5, name is 4-Bromo-3-methylpyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. HPLC of Formula: C4H5BrN2

NaH (60% in mineral oil, 410 mg, 10.2 mmol) is added portionwise to a stirred solution of 4- bromo-3-methylpyrazole (1.69 g, 10.2 mmol) in DMF (20 ml). The resulting mixture is stirred for 1 h at 00C and 4-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (as obtained in preparation 61 , 2.839 g, 10.16 mmol) is added. The resulting pale suspension is heated at 950C for 1h. The reaction is quenched with water and extracted with EtOAc several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 120 g silica gel column on a Combiflash Companion (Isco Inc.) apparatus ( gradient hexanes: TBDME from 1 :0 => 1 :1) to afford the two regioisomers identified by preparation 92 and preparation 93.

The synthetic route of 13808-64-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; WO2008/148867; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 96799-02-9,Some common heterocyclic compound, 96799-02-9, name is 5-(Furan-2-yl)-1H-pyrazol-3-amine, molecular formula is C7H7N3O, 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.

Example 18To a solution of cyanuric chloride (230 mg, 1.25 mmol) in THF (16 mL) was added 4- fluorophenyl-2-ethylamine (0.16 mL, 1.25 mmol) and DIPEA (0. 20 mL, 1.25 mmol) at 0 C. The reaction mixture was let to stir at 0 C to room temperature for 2h. 3-amino-5-(2- furyl)pyrazole (187 mg, 1.25 mmol) and DIPEA (0.20 mL, 1.25 mmol) were added to the above mixture and the resulting mixture was heated with microwave initiator at 150 C for 10 minutes. 1 -methylpiperazine (0.28 mL, 2.50 mmol) and DIPEA (0.44 mL, 2.50 mmol) were added to the mixture and the mixture was heated with microwave initiator at 60 C for 10 minutes. Saturated NaHCO3 in water was added and the mixture was extracted by ethyl acetate (3 x 50 mL). The combined organic was washed by brine, dried over sodium sulfate and concentrated. The residue was chromatographed on a silica gel column eluted with 0-5 % MeOH/DCM afforded 18 as white solid (65 mg, 11 %). 1HNMR (400 MHz, DMSO-d6,80C) delta 12.48 (bs, 1H, NH), 9.52 (bs, 1Eta, NH), 8.55 (bs, 1Eta, NH), 7.71-5.96 (m, 8Eta, Ar-H), 5.12 (bs, 1Eta, CH), 3.67 (b, 4Eta, 2CH2), 2.30 (bs, 4Eta, 2CH2), 2.21 (s, 3Eta, CH3), 1.47 (s, 3Eta, CH3), 1.45 (s, 3Eta, CH3); ESI-MS: calcd for (C23Eta26FN9O) 463, found 464 [M+H]+. HPLC: retention time: 16.82 min. purity: 95%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-(Furan-2-yl)-1H-pyrazol-3-amine, its application will become more common.

Reference:
Patent; ABRAXIS BIOSCIENCE, LLC; TAO, Chunlin; WANG, Qinwei; HO, David; NALLAN, Laxman; POLAT, Tulay; SUN, Xiaowen; DESAI, Neil; WO2010/144394; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 285984-25-0, name is 3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-amine, 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 285984-25-0, category: pyrazoles-derivatives

Example 127; {[3-(tert-butyl)-l-(4-methylphenyl)pyrazol-5-yl]amino}-N-[(2-{[5-bromo-2-methyl- l-(methylethyl)-6-oxohydropyridin-4-yloxy]methyl}-5- fluorophenyl)methyl]carboxamide; [0337] To a solution of 6-{ [2-(aminomethyl)-4-fluorophenyl]methoxy}-5-bromo- 2-methyl-3-(methylethyl)-3-hydropyrimidin-4-one (0.384g, 1.0 mmol) in dichloromethane (15 mL) and saturated solution Of NaHCO3 (15 mL), phosgene (20% in toluene, 1.042 mL, 1.97mmol) was added. The mixture was stirred for 15 min, the organic layer was dried over Na2SO4 and concentrated in vacuo, and the residue was treated with a solution of 3-(tert-butyl)-l-(4-methylphenyl)pyrazole-5-ylamine (0.229g) in dichloromethane (10 mL). The resulting mixture was stirred for 17 h at room temperature. After removal of the volatiles in vacuo the residue was purified by flash chromatography using dichloromethane/hexanes/acetone (5:5:1) as elution to give the title compound (0.366g, 57.2%) as a white solid: mp 133-135 0C; 1H NMR (CD3OD/400MHz) delta 7.44 (m, 1H),7.28 (m,lH), 6.97 (m, IH), 6.29 (s, IH), 5.44 (s, 2H), 4.60 (br.lH), 4.45 (s,2H), 2.57 (s, 3H), 2.37 (s, 3H), 1.54 (d, 6H, J = 6.8 Hz), 1.30 (s, 9H); Anal. Calcd for C31H36BrFN6O3: C, 58.22; H, 5.67; N, 13.14. Found: C, 57.72; H, 5.24; N, 12.76. ES-MS m/z 641.39 & 639.39

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

Reference:
Patent; PHARMACIA & UPJOHN COMPANY LLC; WO2006/40666; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics