Month: August 2021

Electric Literature of 89088-55-1, 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. 89088-55-1, name is 5-Bromo-1-methyl-1H-pyrazol-3-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of compound 11-3 (2.0 g, 5.4 mmol) and K2C03 (2.2 g, 16.2 mmol) in dioxane (40 mL) and H20 (4 mL) were added 5-bromo-l-methyl-lH-pyrazol-3-amine (1.0 g, 5.9 mmol ) and Pd(dppf)Cl2 (395 mg, 540 umol). The mixture was stirred at 90C for 12 h under N2, cooled to rt and concentrated. The residue was purified by prep-TLC (Si02) followed by prep-HPLC. The eluent was adjusted to pH = 8 with sat.NaHC03 and extracted with ethyl acetate (20 mL chi 3). The combined organic layers was dried over Na2S04, filtered and concentrated under reduced pressure to afford 11-4 (114.9 mg, 337.0 umol, 6.2% yield). M+H+ = 340.2 (LCMS); 1H MR (DMSO-i, 400MHz): delta 9.89 (s, 1H), 9.12 (s, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.92 (d, J= 8.6 Hz, 1H), 7.73 (dd, J= 1.5, 8.6 Hz, 1H), 5.67 (s, 1H), 4.63 (br s, 1H), 3.66 (s, 3H), 1.50 (s, 9H).

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, 5-Bromo-1-methyl-1H-pyrazol-3-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; QUENTIS THERAPEUTICS, INC.; VACCA, Joseph P.; LI, Dansu; BETTIGOLE, Sarah; (159 pag.)WO2018/102751; (2018); 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. 1280210-79-8, name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C10H15N3O2

4,6-Dihydro-2H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester(0.30 g, 1.43 mmol) was dissolved in tetrahydrofuran (10 mL).Nitrogen protection, sodium hydride (0.11 g, 2.85 mmol, 60%) was added at 0 C.Slowly rise to room temperature for 1 hour, then cool to 0 C,Add 5-methylthiophene-2-sulfonyl chloride (0.39 g, 1.99 mmol),The reaction was carried out for 6 hours at room temperature. The reaction was quenched by adding water (10 mL) at 0 C.Extracted with ethyl acetate (20 mL×3).The combined organic phases were washed with a saturated sodium chloride solution (10 mL) and dried over anhydrous sodium sulfate, concentrated by suction filtration, and the residue was subjected to silica gel column chromatography[ethyl acetate / petroleum ether (v / v) = 1 / 9] purified,The title compound was obtained (0.40 g, yield 76%).It is a white solid.

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; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Ruyuan Yong Xing Technology Services Co., Ltd.; Li Jianhao; Gu Zheng; Deng Xinshan; Tang Wanjun; Zhang Zongyuan; Kang Panpan; Yuan Weihui; Peng Fei; (49 pag.)CN109942583; (2019); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 19968-17-3, 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 19968-17-3 as follows.

To a solution of 4-bromo-3-trifluoromethyl-lH-pyrazole 33 (0.645 g, 3 mmol) in dimethylformamide (DMF) (50 niL) was added NaH (0.2 g, 9 mmol). The mixture was stirred for 0.5 h at room temperature and the 2-bromo-l ,3-thiazole (0.76 g, 4.5 mmol) was added. The reaction mixture was stirred for 1 h at room temperature. The reaction temperature was raised to 90C and stirred for overnight. The reaction was quenched with MeOH and solvent was removed in vacuo. The residue was treated with water and EtOAc. The organic layer was separated and aqueous was extracted with EtOAc. The combined organic phase was dried over Na2S04, filtered, and concentrated to give crude product. The crude product was purified on ISCO columns. Fractions containing pure product were combined and evaporated to give 34 as a brown oil (0.45 g, 50%).

According to the analysis of related databases, 19968-17-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CALCIMEDICA, INC.; WHITTEN, Jeffrey, P.; CAO, Jianguo; WANG, Zhijun; GREY, Jonathan; ROGERS, Evan; WO2015/54283; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference 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.

To a solution of 1H-pyrazole-3-carbaldehyde (5.00 g, 52.0 mmol, CAS: 3920-50-1) and BnBr (9.34 g, 54.6 mmol) in DMF (50 mL) was added Cs2CO3 (42.4 g, 130 mmol). The reaction mixture was stirred at 25 C. for 1 hour. On completion, the reaction mixture was diluted with water, extracted with ethyl acetate (3×100 mL). The combined organic layers was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (Petroleum ether: Ethyl acetate=20:1) to give the title compound (8.00 g, 83% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) delta 10.02 (s, 1H), 7.44 (d, J=2.4 Hz, 1H), 7.43-7.33 (m, 3H), 7.29-7.24 (m, 2H), 6.85 (d, J=2.4 Hz, 1H), 5.42 (s, 2H).

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

Reference:
Patent; Kymera Therapeutics, Inc.; Mainolfi, Nello; Ji, Nan; Kluge, Arthur F.; Weiss, Matthew M.; Zhang, Yi; (1443 pag.)US2019/192668; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 155377-19-8, 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. 155377-19-8, name is Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 3-trifluoromethyl-lH-pyrazole-4-carboxylic acid ethyl ester (2.5 g, 12.0 mmol), copper (I) iodide (0.69 g, 3.6 mmol) and potassium carbonate (3.49 g, 25.3 mmol) in toluene (12 mL) in a round bottom flask was purged with argon. To the reaction mixture was then added iodobenzene (1.61 mL, 14.4 mmol) and racemic trans- N,N’-dimethyl-cyclohexane-l,2-diamine (1.16 mL, 7.2 mmol). The slurry was heated under Ar in an oil bath at HO0C for 24 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered over a bed of celite. The organic washings were combined and concentrated to give a crude which was purified by silica gel chromatography (Isco 120 g column, 0 -> 30% ethyl acetate/hexanes) to give 1- phenyl-3-trifluoromethyl-lH-pyrazole-4-carboxylic acid ethyl ester (2.91 g, 85%) as an off-white solid. The NMR spectrum obtained on the sample is compatible with its structure.

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 3-(trifluoromethyl)pyrazole-4-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2008/141976; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 5203-77-0, name is 1,3-Dimethyl-1H-pyrazol-5-ol, molecular formula is C5H8N2O, 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 1,3-Dimethyl-1H-pyrazol-5-ol

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.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5203-77-0, its application will become more common.

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

Electric Literature of 35344-95-7, 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. 35344-95-7 name is 1H-Pyrazole-4-carbaldehyde, 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.

To the stirred solution of lH-pyrazole~4~carbaldehyde 46-3 (461.54 mg, 4.80 mmol) and (l-benzy~4~ piperidyl) methanesulfonate 46-2 (1.2 g, 4.46 mmol) in DMF (20 mL) was added cesium carbonate (3.35 g, 10.28 mmol). Reaction mixture was heated at 80C for 16 hours and was then cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. Crude material was purified by combiflash chromatography eluting at 0 1% methanol in dichlorometha e to afford l~(l-benzyl~4- piperidyl)pyrazole-4-carbaldehyde 46-4 (650 mg, 2.41 mmol, 70.42% yield) as brown gum. LC MS: ES+ 269 8.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Pyrazole-4-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Patent; C4 THERAPEUTICS, INC.; VEITS, Gesine, Kerstin; HE, Minsheng; HENDERSON, James, A.; NASVESCHUK, Christopher, G.; PHILLIPS, Andrew, J.; GOOD, Andrew, Charles; (471 pag.)WO2019/191112; (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. 139756-02-8, name is 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide, A new synthetic method of this compound is introduced below., Quality Control of 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide

General procedure: We intended to synthesize compounds based on 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one scaffold by using microwave assisted protocol (Scheme 1). In this direction we started the studies for optimization of synthesis of 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 3a. The optimization studies were initiated by screening of different oxidizing agents as depicted in Table1, see Supplementary data using DMSO:Water in 1:1 proportion to see the conversion in desired product. Amongst all oxidants, the best result was observed with K2S2O8, in equivalence studies for catalyst, 3eq. of catalyst has given maximum yields (Table1, see Supplementary data). Therefore, all reactions were conducted using this condition after optimization of catalyst. However, oxone has also given the product 3a with minor yields. After screening of the catalyst we started study of selectivity for solvent that could affect the formation of 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 3a. The solvent screening was carried out to find out the best conversion, the mixture of DMSO:H2O in 1:1 proportion has given the best results with excellent yields (Table2, see Supplementary data). The microwave protocols were optimized for this reaction as mentioned in Table 3, see Supplementary data; the reactions carried under different microwave Watt powers have given varied results. Wherein, entry 3(b) (Table3, see Supplementary data) was found to be the best condition for maximum conversion. A series of compounds based on 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one scaffold was synthesized using these optimized conditions, wherein, all kind of substrates with diversity around aryl ring were chosen for conversion and in all cases products obtained in good to excellent yields (Table1).

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:
Article; Reddy, G. Lakshma; Guru, Santosh Kumar; Srinivas; Pathania, Anup Singh; Mahajan, Priya; Nargotra, Amit; Bhushan, Shashi; Vishwakarma, Ram A.; Sawant, Sanghapal D.; European Journal of Medicinal Chemistry; vol. 80; (2014); p. 201 – 208;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1128-54-7,Some common heterocyclic compound, 1128-54-7, name is 3-Methyl-1-phenyl-1H-pyrazole, molecular formula is C10H10N2, 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.

A suspension of Preparation 137 (2 g, 12.58 mmol) in water (50 mL) and tert-Butanol (2 mL) was heated at 70C and a solution of KMnO4 (4.97 g, 31.45 mmol) in water (120 mL) was dropwise added and mixture stirred at 70C for 12 h. Crude was filtered through Celite, concentrated and acidified with 2 N HCl. Product was extracted with ethyl acetate, organic layers were combined and washed with brine, dried over sodium sulphate, filtered and concentrated to yield the title compound as a white solid (4% yield). LRMS: m/z 189 (M+1)+ Retention time: 2.50 min (Method B) 1H NMR (400 MHz, DMSO-d6) delta ppm 6.96 (d, J=2.34 Hz, 1 H) 7.40 (t, J=7.42 Hz, 1 H) 7.55 (t, J=8.01 Hz, 2 H) 7.90 (d, J=7.82 Hz, 2 H) 8.61 (d, J=2.34 Hz, 1 H) 12.99 (br. s., 1H).

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

Reference:
Patent; Almirall, S.A.; Erra Sola, Montserrat; Aguilar Izquierdo, Nuria; Carrascal Riera, Marta; Taboada Martinez, Lorena; Navarro Romero, Eloisa; Vidal Juan, Bernat; EP2390252; (2011); 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. 2075-45-8, name is 4-Bromo-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 4-Bromo-1H-pyrazole

To a solution of 4-bromo-1H-pyrazole (3.0 g, 20.4 mmol) in N,N-dimethylformamide (10 mL) was added NaH (60% in mineral oil, 1.0 g, 25 mmol) at 0 C. The reaction mixture was stirred at 0 C. for 10 min. Methyl 2-bromo-2-methylpropanoate (5 mL, 38.67 mmol) was added. The reaction mixture was stirred at room temperature for 1 h before 50 mL of brine was added. The mixture was extracted with ethyl acetate (20 mL*3). The organics were dried with Na2SO4, concentrated and purified by column chromatography (ethyl acetate/petroleum ether, 1:3) to afford methyl 2-(4-bromopyrazol-1-yl)-2-methyl-propanoate (4.7 g, 93.2% yield) as a colorless liquid. LCMS(ESI): [M+H]+=249.0.

According to the analysis of related databases, 2075-45-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Genentech, Inc.; Chan, Bryan; Daniels, Blake; Drobnick, Joy; Gazzard, Lewis; Heffron, Timothy; Huestis, Malcolm; Liang, Jun; Malhotra, Sushant; Mendonca, Rohan; Rajapaksa, Naomi; Siu, Michael; Stivala, Craig; Tellis, John; Wang, Weiru; Wei, BinQing; Zhou, Aihe; Cartwright, Matthew W.; Gancia, Emanuela; Jones, Graham; Lainchbury, Michael; Madin, Andrew; Seward, Eileen; Favor, David; Fong, Kin Chiu; Good, Andrew; Hu, Yonghan; Hu, Baihua; Lu, Aijun; US2018/282328; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics