Month: September 2021

Application of 152120-54-2,Some common heterocyclic compound, 152120-54-2, name is tert-Butyl (((tert-butoxycarbonyl)amino)(1H-pyrazol-1-yl)methylene)carbamate, molecular formula is C14H22N4O4, 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 stirred solution of N,N?-di-Boc-pyrazologuanidine (1,0 g, 3,22 mmol) in dry THF (20 mL) under N2 atmosphere, PPh3 (1,27 g, 4,19 mmol) and crotyl alcohol (0,36 mL, 4,19 mmol) were added. The mixture was cooled to 0 Cand DIAD (0,91 mL, 4,84 mmol) was added dropwise. The mixture was stirred at 0 C for 15 min then at room temperature for 2 h, then it was diluted with AcOEt and washed with water. The aqueous phase was back-extracted with AcOEt. The combined organic phases were washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified with flash chromatography on silica gel, eluting with 10% AcOEt/Hex to give pure compound 9 (0.95 g, 95% yield). 1H NMR (400 MHz CDCl3) delta 7.89 (s, 1H), 7.66 (s, 1H), 6.37 (s, 1H), 5.60 (m, 2H), 4.18 (m, 2H), 1.62 (s, 3H), 1.44 (s, 9H), 1.22 (s, 9H). LC-MS(ES) m/z = 387.1 [M+Na]+, 365.1 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route tert-Butyl (((tert-butoxycarbonyl)amino)(1H-pyrazol-1-yl)methylene)carbamate, its application will become more common.

Reference:
Article; Borgini, Matteo; Orofino, Francesco; Truglio, Giuseppina I.; Balestri, Lorenzo; Botta, Maurizio; Arkivoc; vol. 2019; 4; (2019);,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, 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. Quality Control of 1-Methyl-1H-pyrazole-4-carbaldehyde

1-methyl-1H-pyrazole-4-carbaldehyde previously obtained, malonic acid (4.68g, 45mmol), pyridine (4ml, 50mmol) and piperidine (0.09ml, 1mmol) were placed in a 250 ml flask and heated at 110C for 6h under nitrogen, then the reaction was stopped and cooled. The resulting solution was added with water (100ml), followed by addition of strong aqua dropwise to dissolve all the solids. The solution was then brought to pH~1 with concentrated hydrochloric acid. The precipitate thus obtained was collected by filtration, washed with water several times and then dried in vacuo to give the title compound (2.9g). 1H-NMR (d6-DMSO, 300 MHz) delta3.83 (s, 3H), 6.17 (d, 1H, J=16.2), 7.45 (d, 1H, J=15.9), 7.83 (s, 1H), 8.07 (s, 1H), 12.07 (s, 1H).

The synthetic route of 25016-11-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Institute of Materia Medica, Chinese Academy of Sciences; SHEN, Jianhua; WANG, Yiping; WANG, Kai; EP2725024; (2014); 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. 1572-10-7, name is 3-Amino-5-phenylpyrazole, This compound has unique chemical properties. The synthetic route is as follows., Safety of 3-Amino-5-phenylpyrazole

General procedure: The compound tetronic acid (15) (80 mg, 0.8 mmol) was dissolved in 4 mL of ethanol, followed by addition of terphenyl aldehyde 13a (221.2 mg, 0.8 mmol) and 3-amino-5-phenyl pyrazole 14a (127.2 mg, 0.8 mmol). The reaction mixture was refluxed in ethanol at 78 C for an hour. Then reaction suspension was cooled to room temperature, and the precipitated product was collected by vacuum filtration and washed with ethanol (3 mL), then recrystallized from ethanol to afford pure compound 8a as a white solid, 340 mg in 85% yield. Mp: 273-274 C; 1H NMR (300 MHz, DMSO-d6): delta 4.80 (s, 2H), 5.25 (s, 1H ), 6.89-6.99 (m, 1H), 7.19-7.35 (m, 7H), 7.42-7.52 (m, 4H), 7.65 (dd, 4H, J = 8.8, 11.7 Hz), 8.05 (s, 1H), 10.19 (s, 1H ), 12.56 (s, 1H); 13C NMR (300 MHz, DMSO-d6): delta 30.5, 64.8, 94.4, 99.8, 111.1, 111.3, 113.2, 121.3, 125.4, 126.1, 126.7, 126.9, 127.1, 127.2, 127.3, 128.3, 128.7, 128.8, 132.7, 137, 137.2, 138.8, 139.3, 145.8, 152.7, 157.7, 172.2; MS (ESI): 500 [M+H]+; HRMS (ESI) calcd for C32H23O2N3F [M+H]+ 500.1712; found: 500.1738.

According to the analysis of related databases, 1572-10-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kamal, Ahmed; Tamboli, Jaki R.; Lakshma Nayak; Adil; Vishnuvardhan; Ramakrishna; Bioorganic and Medicinal Chemistry; vol. 22; 9; (2014); p. 2714 – 2723;,
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. 25016-12-0, name is 1,3-Dimethyl-1H-pyrazole-4-carbaldehyde, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

To a suspension of tert-butyl 5-((2-amino-5-chloro-3-nitropyridin-4- yl)amino)hexahydrocyclo- penta[c]pyrrole-2(lH)-carboxylate (0.62 g, 1.60 mmol) and 1,3- dimethylpyrazole-4-carbaldehyde (0.22 g, 1.78 mmol) in EtOH (30.0 mL) was added a freshly prepared aqueous solution of sodium dithionite (6.30 mL, 6.30 mmol, 1.0 mol/L). The mixture was heated at 85 C overnight. The mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v) = 50/1 to 30/1 to 20/1) to afford the title compound as a white solid (0.50g, yield 68%).MS (ESI, pos. ion) m/z: 472.3 [M+H]+; MR (600 MHz, CDC ) delta (ppm): 7.87 (s, 1H), 7.72 (s, 1H), 5.49 – 5.39 (m, 1H), 5.03 (d, J = 8.4 Hz, 1H), 3.92 (s, 3H), 3.58 – 3.48 (m, 2H), 3.46 – 3.33 (m, 2H), 2.80 – 2.72 (m, 2H), 2.69 – 2.60 (m, 5H), 1.50 (s, 9H), 1.48 – 1.40 (m, 2H).

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; SUNSHINE LAKE PHARMA CO., LTD.; CALITOR SCIENCES, LLC; XI, Ning; LI, Xiaobo; LI, Mingxiong; ZHANG, Tao; HU, Haiyang; WU, Yanjun; (139 pag.)WO2018/169700; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 288148-34-5, 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. 288148-34-5 name is 1-Methyl-1H-pyrazole-4-sulfonyl chloride, 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.

Reference Example 106; tert-butyl ( {4-fluoro-5- (2-fluoropyridin-3-yl) -1- [ (1-methyl- lH-pyrazol-4-yl) sulfonyl] -lH-pyrrol-3- yl }methyl) methylcarbamate; To a solution of tert-butyl { [4-fluoro-5- (2- fluoropyridin-3-yl) -lH-pyrrol-3-yl]methyl }methylcarbamate (324 mg) in tetrahydrofuran (20 itiL) was added sodium hydride (60% in oil, 121 mg) at room temperature and the mixture was stirred for 15 min. 15-Crown-5 (664 mg) was added dropwise and the mixture was stirred for 5 min. l-Methyl-lH-pyrazole-4- sulfonyl chloride (362 mg) was added, and the mixture was further stirred for 30 min. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=l:l) to give the title compound as a colorless oil (yield 460 mg, 98%) .1H-NMR (CDCl3) delta: 1.48(9H,s), 2.88(3H,s), 3.87(3H,s),4.27(2H,brs) , 7.21 (IH, d, J=4.9Hz) , 7.30 (IH, t, J=6.1) , 7.41(lH,br), 7.42(lH,s), 7.86 (IH, t, J=8. IHz) ,8.29 (lH,d, J=4.9Hz) .

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

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2008/108380; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 5334-40-7, These common heterocyclic compound, 5334-40-7, name is 4-Nitro-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.

4-(morpholinomethyl)phenyl-1,2-diamine (2.3 g, 1.11 mmol),4-nitro-1H-pyrazole-3-carboxylic acid (1.57 g, 1 mmol),EDCl (2.13 g, 1.11 mmol) and HOBt (1.5 g, 1.11 mmol)Dissolved in dry DMF (25 mL) and stirred at rt overnight.The solvent was removed under reduced pressure, was added glacial acetic acid (40 mL), was heated to reflux for 3 hours.The solvent was removed under reduced pressure and purified by column (dichloromethane/methanol (v/v) = 10/1).Then wash with methanol (10 mL),Methanol-insoluble product as a yellow solid that is, to give the product (0.9g, 27percent).

The synthetic route of 5334-40-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Liu Bing; Zhang Yingjun; Zhang Jiquan; Li Yanping; Yang Xueqi; Zhang Jiancun; Zheng Changchun; (91 pag.)CN104211692; (2019); B;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 1120-82-7, The chemical industry reduces the impact on the environment during synthesis 1120-82-7, name is (1H-Pyrazol-1-yl)methanol, I believe this compound will play a more active role in future production and life.

To a Schlenk tube was added Cul (9.5 mg), Pd(Ph3P)2Cl2 (35 mg), compound A (1085) (188 mg, 0.5 mmol), TMS acetylene (98 mg, 1.0 mmol), DMF (2 mL), and Et3N (0.5 mL). The reaction mixture was heated at 80 C for 12 hours. The reaction mixture was cooled and treated with EtOAc and brine. The organic layer was separated, dried, and evaporated. The residue was chromatographed on silica gel to give the TMS intermediate. The TMS intermediate was treated with TBAF (0.6 mmol) in 2 mL dry THF for 15 min. The residue was chromatographed on silica gel to give compound C (115 mg, 17% yield). (1086) [0621] To a solution of (lH-pyrazol-l-yl)methanol (196 mg, 2 mmol) in DCM (2 mL) was added methanesulfonyl chloride (4 mmol). The mixture was stirred at 0 C for 10 minutes then Et3N (6 mmol) was slowly added. After stirring at r.t. for 30 min, all volatiles were removed. 3-(4-Hydroxy-l-oxoisoindolin-2-yl)piperidine-2,6-dione (520 mg, 2 mmol), KHC03 (400 mg, 4 mmol), KI (10 mg) and 4 mL CH3CN were added to the residue. The mixture was heated at reflux overnight. The residue was chromatographed on silica gel to give compound D (210 mg, 31% yield). (1087) [0622] To a solution of compound D (210 mg, 0.62 mmol) in acetic acid (4 mL) was added NIS (321 mg, 0.75 mmol). The reaction was stirred for 1 h prior to being concentrated. The residue was purified by HPLC to afford compound E (156 mg, 54%). ESI-MS: 481.05. (1088) [0623] To a Schlenk tube was added Cul (2 mg), Pd(Ph3P)2Cl2 (4 mg), compound C (1089) (20 mg, 0.06 mmol), compound E (28 mg, 0.06 mmol), DMF (2 mL), and Et3N (0.5 mL). The reaction mixture was heated at 80 C for 12 hours. The reaction mixture was cooled and treated with EtOAc and brine. The organic layer was separated, dried, and evaporated. The residue was subjected to HPLC purification to afford Cpd. No. 82 (25 mg, 64% yield). ESI-MS: 674.05.

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, (1H-Pyrazol-1-yl)methanol, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF MICHIGAN; WANG, Shaomeng; HU, Yang; QIN, Chong; XU, Fuming; HU, Jiantao; ZHOU, Bing; CHEN, Zhou; FERNANDEZ-SALAS, Ester; BAI, Longchuan; McEACHERN, Donna; (198 pag.)WO2018/52945; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 5952-93-2, 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. 5952-93-2, name is Methyl 1-methyl-1H-pyrazole-4-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To a solution of methyl 1-(methylcarbamoyl)-1H-pyrazole-3- carboxylate, Example 395.1 (0.943 g, 5.15 mmol) in MeOH (10 mL, 247 mmol), was added hydrazine (0.236 mL, 10.30 mmol) at RT. The resulting mixture was stirred at RT for 24 h. The mixture was then concentrated in vacuo and the residue was dissolved in water (100 mL). The aqueous solution was lyophilized to give the title compound (943 mg). LCMS-ESI (pos.): 184.1 (M+H)+.

The synthetic route of Methyl 1-methyl-1H-pyrazole-4-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; CHEN, Ning; CHEN, Xiaoqi; CHEN, Yinhong; CHENG, Alan C.; CONNORS, Richard V.; DEIGNAN, Jeffrey; DRANSFIELD, Paul John; DU, Xiaohui; FU, Zice; HARVEY, James S.; HEATH, Julie Anne; HEUMANN, Lars V.; HORNE, Daniel B.; HOUZE, Jonathan; KALLER, Matthew R.; KAYSER, Frank; KHAKOO, Aarif Yusuf; KOPECKY, David J.; LAI, Su-Jen; MA, Zhihua; MEDINA, Julio C.; MIHALIC, Jeffrey T.; NISHIMURA, Nobuko; OLSON, Steven H.; PATTAROPONG, Vatee; SWAMINATH, Gayathri; WANG, Xiaodong; WANSKA, Malgorzata; YANG, Kevin; YEH, Wen-Chen; (700 pag.)WO2018/97945; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 1353100-91-0, 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. 1353100-91-0 name is Ethyl 3-bromo-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.

Concentrated sulfuric acid (0.45 mL, 4.8 mmol) was added to a mixture of ethyl 3-bromo-1H-pyrazole-4-carboxylate (1.0 g, 4.6 mmol) and tert-amyl alcohol (3.0 mL, 27 mmol). The reaction was heated to 100 C. for 2.5 hours. The reaction was then cooled to room temperature and left stirring overnight. The reaction was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated to yield ethyl 3-bromo-1-tert-pentyl-1H-pyrazole-4-carboxylate (1.3 g) as a crude brown oil.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 3-bromo-1H-pyrazole-4-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; Pfizer Inc; US2012/108619; (2012); 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.

A solution of 5-cyclopropyl-1H-pyrazol-3-amine (0.267 g, 2.17 mmol) and 2,4,6-trichloroquinazoline (0.432 g, 2.17 mmol) in dimethylformamide (DMF) (10 mL) was treated with EtN(i-Pr)2 (0.49 mL, 2.82 mmol) and stirred for 4 h at 0 C. The reaction mixture was poured over ice water. The solid was collected by filtration and dried in air to provide compound 5 without further purification [16]. The yield was 74.6%.

The synthetic route of 175137-46-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wu, Tianxiao; Pang, Yu; Guo, Jing; Yin, Wenbo; Zhu, Mingyue; Hao, Chenzhou; Wang, Kai; Wang, Jian; Zhao, Dongmei; Cheng, Maosheng; Molecules; vol. 23; 2; (2018);,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics