Month: July 2021

Reference of 31037-02-2, 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. 31037-02-2 name is Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate, 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.

EXAMPLE IX.5 This Example illustrates a preparation of ethyl 5-(4,4-difluorobut-3-enylthio)-1-methylpyrazol-4-yl carboxylate (Compound IX.34). Bis-(4,4-difluorobut-3-enyl)disulfide (2.90 g) and tert.butyl nitrite (1.22 g) in acetonitrile (40 cm3) were heated to 60 C. under an atmosphere of nitrogen. To the stirred solution was added dropwise ethyl 5-amino-1-methylpyrazol-4-yl carboxylate (1.00 g) in acetonitrile (10 cm3). On complete addition the reaction solution was heated for 2 hours at 60 C., evaporated under reduced pressure and fractionated by chromatography (silica; hexane:diethyl ether, 5:1 by volume) to give Compound IX.34 (yield 42%). M+ =276; 1 H NMR: delta 1.38(3H,t); 2.20(2H,m); 3.05(2H,t); 3.97(3H,s); 4.25(1H,m); 4.34(2H,q); 7.98(1H,s); (oil).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; Zeneca Limited; US5705516; (1998); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 82560-12-1,Some common heterocyclic compound, 82560-12-1, name is 3-Amino-5-tert-butylpyrazole, molecular formula is C7H13N3, 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 j04: 3-Tert-butyl-1 H-pyrazol-5-amine (J-lll) (1 eq., 40 g) was dissolved in dilute HCI (120 ml of HCI in 120 ml of water) and mixed dropwise with NaNO2 (1.03 eq., 25 g in 100 ml) at 0 – 5 C over a period of 30 min. After stirring for 30 minutes, the reaction mixture was neutralised with Na2C03. A diazonium salt obtained by reaction of KCN (2.4 eq., 48 g), water (120 ml) and CuCN (1.12 eq., 31 g) was added dropwise to the reaction mixture within 30 min and the mixture was stirred for a further 30 min at 75 C. After complete reaction, the reaction mixture was extracted with EE (3 x 500 ml), the combined organic phases were dried over sodium sulphate and the solvent was removed under vacuum. The purification (Si02, 20 % EE/hexane) of the residue by column chromatography produced a white solid (J- IV) (6.5 g, 15.1 % yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Amino-5-tert-butylpyrazole, its application will become more common.

Reference:
Patent; GRUeNENTHAL GMBH; FRANK, Robert; CHRISTOPH, Thomas; FRORMANN, Sven; WO2012/62463; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3398-16-1, 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. 3398-16-1, name is 4-Bromo-3,5-dimethylpyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a dry three-necked flask with a magnetic rotor was added 4-bromo-3,5-dimethylpyrazole (3.5714 g, 20 mmol, 98%, 1.0 eq.), phenylboronic acid (2.9552 g, 24 mmol, 99%, 1.2 equivalents),Palladium acetate (0.1123 g, 0.5 mmol, 0.025 equivalent), ligand S-Phos (0.5027 g, 1.2 mmol, 98%, 0.06 equivalent), 1,4-dioxane (60 mL) and potassium carbonate (8.2920 g, 60 mmol, 3.0 eq.) of aqueous solution (20 mL).Nitrogen was bubbled for 15 minutes and then the reaction flask was placed in a 115 C oil bath.After stirring for 15 hours, the reaction was monitored by thin layer chromatography. It was cooled to room temperature and extracted with dichloromethane (20 mL×3).All organic phases were combined and dried over anhydrous sodium sulfate.Filtration, concentration, and purification of the crude product by flash chromatography on silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3/1 – 1/2) to give 3,5-dimethyl-4-phenyl -1H-imidazole,The white solid was 3.0773 g, and the yield was 89%.

The synthetic route of 4-Bromo-3,5-dimethylpyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhejiang University of Technology; Ruisheng Optoelectric Science And Technology (Changzhou) Co., Ltd.; Li Guijie; Dai Jianxin; She Yuanbin; Chen Shaohai; (127 pag.)CN108659050; (2018); A;,
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. 876343-24-7, name is 1-Ethyl-1H-pyrazol-4-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 1-Ethyl-1H-pyrazol-4-amine

EXAMPLE 187: 4-[4-(l-EthyMNo.-pyrazol-4-ylamino)-7No.-pyrroIo[2,3-“npyrimidin-6-yI]-3,6-dihydro-2No.-pyridine-l-carboxylic acid fcrf-butyl ester.; [527] A mixture of 4-(4-chloro-7No.-pyrrolo[2,3 -d]pyrimidin-6-yl)-3 ,6-dihydro-2No.-pyridine-1-carboxylic acid fert-butyl ester (HOmg, 0.33mmol) and l-ernyl-4-amino-l./:/’-pyrazole (44mg, 0.39mmol) in 1-butanol (3mL) was heated at 120°C overnight, LC-MSshowed the desired product and some de-Boc product. After the mixture was cooled to rt, itwas diluted with methylene chloride (3mL), then AyV-diisopropylethylamine (0.1 ImL,0.66mmol) and di-tert-butyldicarbonate (72mg, 0.33mmol) were added, the resulting mixturewas stirred at rt for 30min. The mixture was diluted with EtOAc (30mL), then washed withbrine (20mL), and dried over anhydrous sodium sulfate. The solvent was evaporated underreduced pressure, and the residue was crystallized with EtOAc to give, the title compound asan off-white solid. LC-MS (ES, Pos.): 410 [MH*]. ‘HNMR (CDC13, 400 MHz): 8 = 1.51 (s,9H), 1.56 (t, J = 7.3 Hz, 3H), 2.50 (m, 2H), 3.66 (m, 2H), 4.16 (m, 2H), 4.22 (q, J = 7.3 Hz,2H), 6.04 (s, 1H), 6.17 (s, 1H), 6.57 (s, 1H), 7.56 (s, 1H), 7.95 (s, 1H), 8.38 (s, 1H), 10.96 (brs, 1H).

The synthetic route of 876343-24-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; OSI PHARMACEUTICALS, INC.; WO2006/17443; (2006); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 18213-75-7, A common heterocyclic compound, 18213-75-7, name is 5-Amino-1-methyl-1H-pyrazole-4-carboxamide, molecular formula is C5H8N4O, 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.

Isopropyl chloroformate (1.95 g, 14.3 mmol) and N-methylmorpholine (1.44 g, 14.3 mmol) were added to a solution of 4,4,4-trifluorobutanoic acid (2.03 g, 14.3 mmol) in THF (40 mL) at -15C. The solution was stirred for 10 min then cooled to -50C and a solution of 5-amino-1-methyl-1H-pyrazole-4-carboxamide (2.0 g, 14.3 mmol) and DIEA (2.49 ml, 14.3 mmol) in DMF (20 ml) was added. The solution was allowed to slowly warm to ambient temperature over 2 h. The solution was diluted with EtOAc and washed with brine. The organic layer was dried, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography using 0% to 15% MeOH in CH2CI2 gradient to give the title compound.

The synthetic route of 18213-75-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; HAN, Xiaoqing; WHITEHEAD, Alan; RAGHAVAN, Subharekha; CERNAK, Timothy, A.; DREHER, Spencer; GROEPER, Jonathan; GUO, Jian; ZHANG, Yong; WO2015/88886; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

4149-06-8, name is 3-Amino-1-phenyl-1H-pyrazol-5(4H)-one, 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. category: pyrazoles-derivatives

General procedure: A mixture of substituted 3-(2-aryl-2-oxoethylidene)indolin-2-one 1 (1 mmol), 1,3-dimethylurea (2, 1.2 mmol) or 5-amino-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (4, 1 mmol), PTSA·H2O (0.3 mmol), and MeCN (5 mL) was added to a 25 mL flask and reacted at 80 C (monitored by TLC) about 2 h. After completion, the mixture was cooled to r.t. and the precipitate obtained was isolated by filtration and drying. Compounds 3 or 5 were purified by recrystallization (DMF or EtOH).

The synthetic route of 4149-06-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Dai, Lei; Shu, Ping; Wang, Zhansheng; Li, Qingyang; Yu, Qiuyu; Shi, Yanhui; Rong, Liangce; Synthesis; vol. 49; 3; (2017); p. 637 – 646;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 113100-53-1,Some common heterocyclic compound, 113100-53-1, name is 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, molecular formula is C6H5F3N2O2, 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 suspension of 6-(2-amino-5-chlorothiazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (0.100 g, 0.41 mmol) and 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (0.087 g, 0.45 mmol), and pyridine (0.15 mL, 1.83 mmol in acetonitrile (5 mL) in a sealed tube was added propylphosphonic anhydride solution (50 wt % in ethyl acetate, 0.60 mL, 1.02 mmol). The sealed tube was heated to 100 C. for over night and the precipitation formed. After cooling, the precipitate was collected by filtration and washed with cold 1:1 acetonitrile/water to give 1-methyl-N-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (0.120 g, 70%). 1H NMR (400 MHz, DMSO-d): delta 12.61 (bs, 1H), 10.19 (s, 1H), 8.76 (s, 1H), 7.74 (m, 1H), 7.69 (dd, 1H, J=8.4, 2.0 Hz), 7.50 (s, 1H), 6.90 (d, 1H, J=8.0 Hz), 4.00 (s, 3H), 2.92 (t, 2H, J=7.2 Hz), 2.48 (partial masked under d-DMSO, m, 2H); MS (ESI): Calcd. For C18H14F3N5O2S: 421, found 422 (M+1)+.

The synthetic route of 113100-53-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nantbio, Inc.; Tao, Chunlin; Nallan, Laxman; Ho, David G.; Wang, Qinwei; Weingarten, Paul; Juncker-Jensen, Anna B.; (121 pag.)US2018/201610; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 34091-51-5, name is 5-Iodo-1-methyl-1H-pyrazole, 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. Recommanded Product: 34091-51-5

Production Example 11 1′-(4-Fluorophenyl)-2-methyl-1’H,2H-3,4′-bipyrazole Under a nitrogen atmosphere, a mixture of 5-iodo-1-methyl-1H-pyrazole (600 mg), [1-(4-fluorophenyl)-1H-pyrazol-4-yl]boronic acid (650 mg), tetrakistriphenylphosphine palladium (166 mg), 2 M sodium carbonate aqueous solution (2.9 mL), ethanol (3.0 mL) and toluene (6.0 mL) was stirred at 100 C. for 4 hours. Thereafter, water was added to the reaction solution, and the obtained mixture was then extracted with ethyl acetate. The organic layer was concentrated under a reduced pressure, and the residue was then purified by column chromatography (silica gel cartridge, hexane:ethyl acetate=9:1 to ethyl acetate), so as to obtain the title compound (450 mg) in the form of a light yellow solid. 1H NMR (600 MHz, CHLOROFORM-d) delta ppm 3.97 (s, 3H) 6.34 (d, J=1.83 Hz, 1H) 7.14-7.22 (m, 2H) 7.46-7.53 (m, 1H) 7.66-7.72 (m, 2H) 7.83 (s, 1H) 7.98 (s, 1H); MS (ESI pos.) m/z: 243 [M+H]+

The synthetic route of 5-Iodo-1-methyl-1H-pyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAISHO PHARMACEUTICAL CO., LTD.; Nakamura, Toshio; Sakagami, Kazunari; Konishi, Kazuhide; Yamamoto, Kanako; Masuda, Seiji; Matsuda, Yohei; Okada, Kumiko; Shibata, Tsuyoshi; Ohta, Hiroshi; Yasuhara, Akito; Kawamoto, Hiroshi; Amada, Hideaki; Urabe, Hiroki; Nishikawa, Rie; Kashiwa ASHIWA, Shuhei; US2013/137865; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 25016-20-0, 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. 25016-20-0, name is 1-Methyl-1H-pyrazole-3-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

Example 67;(i?)-(l-Methyl-l/-r-pyrazoI-3-yl)(l-(4-(trifluoromethyl)phenyl)-3,4-dihydroiso- quinoIin-2(lH)-yl)methanone; A solution of (R)- -(4-(trifluoromethyl)phenyl)- 1,2,3, 4-tetrahydroisoquinoline (58 mg, 0.21 mmol, example 30, step 1) in DMF (1 mL) was added 1-methyl-leta- pyrazole-3-carboxylic acid (Fluorochem, 34 mg, 0.27 mmol), 1-hydroxybenzo- triazole hydrate (42 mg, 0.27 mmol), and JV-((isopropylimino)methylene)propan- 2-amine (66 muL, 0.42 mmol). The resulting mixture was then stirred at RT for 16 h. Then, the mixture was filtered and the filtrate was purified by preparative HPLC to give the target compound. The product was dissolved in MeOH and passed through PL-HCO3 MP resin and the resin was washed with MeOH (2 x 0.3 mL). The combined filtrates were concentrated and dried under vacuum to give the title compound as a light-yellow solid. MS (ESI, positive ion) m/z: 386 (M+H).

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

Reference:
Patent; AMGEN INC.; WO2009/73203; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

42027-81-6, name is 2-(4-Nitro-1H-pyrazol-1-yl)ethanol, 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. Product Details of 42027-81-6

To a stirred solution of 2-(4-nitro-1H-pyrazol-1-yl)ethanol 17 (2.0 g, 1.23 mmol) in EtOH (25 mL), 0.40 g of Pd(OH)2 added and then stirred reaction under H2 gas atm for 1 4h. After the completion of reaction (TLC monitoring) the reaction mixture was filtered through celite bed, washed with MeOH, concentrated the solvent and the crude compound was purified by triturating with ether and pentane to give 2-(4-amino-1H- pyrazol-1-yl)ethanol precursor-07 as brown solid (1.30 g, 81% yield). MS: 128.07 (M+H).

The synthetic route of 42027-81-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JUBILANT BIOSYS LIMITED; VENKATESHAPPA, Chandregowda; SIVANANDHAN, Dhanalakshmi; BAKTHAVATCHALAM, Rajagopal; KETHIRI, Raghava Reddy; VISWANADHAN, Vellarkad Narayana; GIRI, Sanjeev; WO2015/25197; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics