866837-96-9 | pyrazoles-derivatives

Dressen, Darren’s team published research in Journal of Medicinal Chemistry in 2007 | CAS: 866837-96-9

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.COA of Formula: C12H13N3O2

COA of Formula: C12H13N3O2On October 18, 2007 ,《Preparation and Optimization of a Series of 3-Carboxamido-5-phenacylaminopyrazole Bradykinin B1 Receptor Antagonists》 was published in Journal of Medicinal Chemistry. The article was written by Dressen, Darren; Garofalo, Albert W.; Hawkinson, Jon; Hom, Dennis; Jagodzinski, Jacek; Marugg, Jennifer L.; Neitzel, Martin L.; Pleiss, Michael A.; Szoke, Balazs; Tung, Jay S.; Wone, David W. G.; Wu, Jing; Zhang, Heather. The article contains the following contents:

The B1 receptor is an attractive target for the treatment of pain and inflammation. 3-Carboxamido-5-phenacylamino pyrazole B1 receptor antagonists are described that exhibit good potency against B1 and high selectivity over B2. Initially, N-unsubstituted pyrazoles were studied, but these compounds suffered from extensive glucuronidation in primates. This difficulty could be surmounted using N-substituted pyrazoles. Optimization efforts culminated in compound 41 {4-bromo-5-[(2-chlorobenzoyl)amino]-1-phenyl-N-[2-[1-(4-pyridinyl)-4-piperidinyl]ethyl]-1H-pyrazole-3-carboxamide}, which has high receptor potency and metabolic stability. In the experiment, the researchers used many compounds, for example, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9COA of Formula: C12H13N3O2)

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Bagal, Sharan K.’s team published research in Journal of Medicinal Chemistry in 2019 | CAS: 866837-96-9

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.SDS of cas: 866837-96-9

Bagal, Sharan K.; Omoto, Kiyoyuki; Blakemore, David C.; Bungay, Peter J.; Bilsland, James G.; Clarke, Philip J.; Corbett, Matthew S.; Cronin, Ciaran N.; Cui, J. Jean; Dias, Rebecca; Flanagan, Neil J.; Greasley, Samantha E.; Grimley, Rachel; Johnson, Eric; Fengas, David; Kitching, Linda; Kraus, Michelle L.; McAlpine, Indrawan; Nagata, Asako; Waldron, Gareth J.; Warmus, Joseph S. published an article on January 10 ,2019. The article was titled 《Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.SDS of cas: 866837-96-9 The information in the text is summarized as follows:

Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are activated by hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4). Moreover, the NGF antibody tanezumab has provided clin. proof of concept for inhibition of the TrkA kinase pathway in pain leading to significant interest in the development of small mol. inhibitors of TrkA. However, achieving TrkA subtype selectivity over TrkB and TrkC via a Type I and Type II inhibitor binding mode has proven challenging and Type III or Type IV allosteric inhibitors may present a more promising selectivity design approach. Furthermore, TrkA inhibitors with minimal brain availability are required to deliver an appropriate safety profile. Herein, we describe the discovery of a highly potent, subtype selective, peripherally restricted, efficacious, and well-tolerated series of allosteric TrkA inhibitors that culminated in the delivery of candidate quality compound 23. In the experiment, the researchers used many compounds, for example, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9SDS of cas: 866837-96-9)

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Silvestri, Romano’s team published research in Journal of Medicinal Chemistry in 2008 | CAS: 866837-96-9

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylateOn March 27, 2008, Silvestri, Romano; Cascio, Maria Grazia; La Regina, Giuseppe; Piscitelli, Francesco; Lavecchia, Antonio; Brizzi, Antonella; Pasquini, Serena; Botta, Maurizio; Novellino, Ettore; Di Marzo, Vincenzo; Corelli, Federico published an article in Journal of Medicinal Chemistry. The article was 《Synthesis, cannabinoid receptor affinity, and molecular modeling studies of substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides》. The article mentions the following:

The new 1-phenyl-5-(1H-pyrrol-1-yl)pyrazole-3-carboxamides were compared with the reference compounds AM251 and SR144528 for cannabinoid hCB1 and hCB2 receptor affinity. Compounds bearing 2,4-dichlorophenyl or 2,4-difluorophenyl groups at position 1 and 2,5-dimethylpyrrole moiety at position 5 of the pyrazole nucleus were generally more selective for hCB1. On the other hand, the N-cyclohexyl group at the 3-carboxamide was the determinant for the hCB2 selectivity, in particular when a 3,4-dichlorophenyl group was also present at position 1. Compound I was the most selective ligand for the hCB1 receptor (Ki (CB2)/Ki (CB1) = 140.7). Derivative II, the most potent hCB1 ligand (Ki = 5.6 nM), was equipotent to AM251 and behaved as an inverse agonist in the cAMP assay (EC50 ∼1 nM). The carbonyl oxygen of both I and II formed a H-bond with K3.28(192), while the substituents at the nitrogen fitted in a pocket formed by lipophilic residues. This H-bonding interaction was proposed to account for the high affinity for receptors’ inactive state and the inverse agonist activity. The experimental part of the paper was very detailed, including the reaction process of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9Name: Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate)

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Arikawa, Yasuyoshi’s team published research in Bioorganic & Medicinal Chemistry Letters in 2015 | CAS: 866837-96-9

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.Electric Literature of C12H13N3O2

Electric Literature of C12H13N3O2On May 15, 2015 ,《Synthetic studies of five-membered heteroaromatic derivatives as potassium-competitive acid blockers (P-CABs)》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Arikawa, Yasuyoshi; Hasuoka, Atsushi; Nishida, Haruyuki; Hirase, Keizo; Inatomi, Nobuhiro; Takagi, Terufumi; Tarui, Naoki; Kawamoto, Makiko; Imanishi, Akio; Itoh, Fumio; Kajino, Masahiro. The article conveys some information:

On the basis of a series of novel and potent potassium-competitive acid blockers represented by 1-sulfonylpyrrole derivative I, we prepared several five-membered heterocyclic analogs II [Ht = S, N, O containing heterocycle] and evaluated their H+,K+-ATPase activities in vitro. We also assessed the role of the methylaminomethyl side chain by comparison with methylamino and ethylamino derivatives We observed that the five-membered core ring and its orientation affect inhibitory activity and that the methylaminomethyl moiety is the best side chain. On the basis of potency and ligand-lipophilicity efficiency, compound I remains the most drug-like of the compounds studied to date. This study revealed the factors necessary for potent H+,K+-ATPase inhibition, such as differences in electron d., the properties of the lone pair at each apical position of the heteroaromatic ring, and the geometry of the substituents. After reading the article, we found that the author used Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9Electric Literature of C12H13N3O2)

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

14-Sep-2021 News The important role of 866837-96-9

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, and friends who are interested can also refer to it.

Related Products of 866837-96-9, 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. 866837-96-9 name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-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.

Pyridine (12.9 mL, 161 mmol) was added to a solution of ethyl 5-amino-1-phenyl-1H- pyrazole-3-carboxylate (9.32 g, 40.3 mmol) and 5-bromo-2-chlorobenzoic acid (10.4 g,44.3 mmol) in 2-methyl-tetrahydrofuran (100 mL). The reaction was heated to 85C before the addition of propylphosphonic anhydride (38.5 mL, 60.4 mmol, 50% solution in EtOAc) drop-wise. The reaction was heated at 85C for 16 hours before cooling to room temperature. The organic solution was washed with saturated aqueous sodium hydrogen carbonate solution (3 x 25 mL), saturated brine (30 mL) and concentrated invacuo. The resulting solid was triturated with TBME (5 x 50 mL) to afford the titlecompound (13.7 g, 76%).1H NMR (400MHz, CDCI3): O ppm 1.42 (t, 3H), 4.44 (q, 2H), 7.25 (d, 1H), 7.39 (5, 1H),7.51 (m, 5H), 8.02 (d, 1H), 8.43 (5, 1H).LCMS Rt = 3.13 minutes MS mlz 448 [M+H]

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; PFIZER INC.; BAGAL, Sharanjeet Kaur; CUI, Jingrong Jean; GREASLEY, Samantha Elizabeth; LUNNEY, Elizabeth Ann; MCALPINE, Indrawan James; NAGATA, Asako; NINKOVIC, Sacha; OMOTO, Kiyoyuki; SKERRATT, Sarah Elizabeth; STORER, Robert Ian; WARMUS, Joseph Scott; WO2015/170218; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

September 9,2021 News Sources of common compounds: 866837-96-9

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

Electric Literature of 866837-96-9,Some common heterocyclic compound, 866837-96-9, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, molecular formula is C12H13N3O2, 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.

5-(3,3-Dimethyl-2-oxo-butylamino)-1 -phenyl-1 H-pyrazole-3-carboxylic acid ethyl ester; O,6g (25,9mmol) of 5-Amino-1 -phenyl-1 H-pyrazole-3-carboxylic acid ethyl ester are dissolved in 50ml DMF, 4,65g (25,9mmol) 1 -bromopinacolone and 16g (49.1 mmol, 1 ,9eq) of Cs2CO3 are added and the resulting mixture is heated to 100C for4hours.The reaction mixture is filtrated and the solvent removed in vacuo, the residue is subjected to preparative HPLC chromatography to obtain 2g (23%) of the product.

Reference:
Patent; SANOFI; RUF, Sven; SADOWSKI, Thorsten; HORSTICK, Georg; SCHREUDER, Herman; BUNING, Christian; OLPP, Thomas; WIRTH, Klaus; WO2012/101199; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

New downstream synthetic route of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

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.

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. 866837-96-9, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., Formula: C12H13N3O2

A solution of 5-(6-((tert-butoxycarbonyl)amino)pyridin-2-yl)-2,4-dichlorobenzoic acid (Preparation 24, 620 mg, 1.62 mmol), ethyl 5-amino-1-phenyl-1 H-pyrazole-3- carboxylate (374 mg, 1.62 mmol) and DIPEA (0.847 mL, 4.86 mmol) in 2- methyltetrahydrofuran (15 mL) was heated under nitrogen to 85C. To the solution was added T3P (50% in EtOAc; 2.90 mL, 4.86 mmol) dropwise over 5 minutes. The reaction was heated at 85C for 5 hours before cooling to room temperature and partitioning between saturated aqueous NaHCC solution (30 mL) and EtOAc (20 mL). The aqueous layer was washed with EtOAc (20 mL), the organic layers combined, dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 30-50% TBME in heptanes to afford the title compound as a white solid (750 mg, 77%). 1 H NMR (400MHz, CDCI3): delta ppm 1 .41 (t, 3H), 1.56 (s, 9H), 4.45 (m, 2H), 7.01 (s, 1 H), 7.30 (d, 1 H), 7.40 (s, 1 H), 7.50-7.62 (m, 5H), 7.73 (t, 1 H), 7.97 (d, 1 H), 8.14 (s, 1 H), 8.42 (s, 1 H).

Reference:
Patent; PFIZER INC.; BAGAL, Sharanjeet Kaur; CUI, Jingrong Jean; GREASLEY, Samantha Elizabeth; LUNNEY, Elizabeth Ann; MCALPINE, Indrawan James; NAGATA, Asako; NINKOVIC, Sacha; OMOTO, Kiyoyuki; SKERRATT, Sarah Elizabeth; STORER, Robert Ian; WARMUS, Joseph Scott; WO2015/159175; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Simple exploration of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

Reference of 866837-96-9,Some common heterocyclic compound, 866837-96-9, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, molecular formula is C12H13N3O2, 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.

1 -Phenyl-5-(pyridin-2-ylamino)-1 H-pyrazole-3-carboxylic acid; 200mg (0,865 mmol) of 5-Amino-1 -phenyl-1 H-pyrazole-3-carboxylic acid ethyl ester were dissolved in 5 ml DMF and 108mg (0,95 mmol, 1 .1 eq) of 2-Chloropyridine, 620mg (1 ,9mmol, 2,2eq) of Cs2C03, 20mg (0, 1 eq) of palladium(ll)acetate and 60mg of xantphos (0, 12eq) were added and the resulting mixture heated to 100C for 6 hours. The mixture was filtered over a pad of Celite and 2 ml of 1 N NaOH (2mmol, 2,3eq) were added together with 2ml of EtOH. After stirring overnight at RT the crude reaction mixture was subjected to HPLC chromatography delivering 60mg of product. (Yield: 25%)

A new synthetic route of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

To a solution of ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (498 mg) synthesized according to the method described in WO2004/98589 in N,N-dimethylacetamide (10 mL) were added N-ethyldiisopropylamine (417 mg) and benzoyl chloride (453 mg) at room temperature. After stirring at the same temperature for 18 hr, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=6:1?3:1) to give the title compound as colorless crystals (yield 550 mg, yield 76%). 1H-NMR(CDCl3)delta:1.42(3H,t,J=7.2Hz), 4.44(2H,q,J=7.2Hz), 7.36(1H,s), 7.43-7.59(8H,m), 7.69-7.73(2H,m), 7.95(1H,brs).

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2196459; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Discovery of 866837-96-9

The synthetic route of 866837-96-9 has been constantly updated, and we look forward to future research findings.

866837-96-9, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, 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. Safety of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

11512] A solution of ethyl 5-amino-i-phenyl-1H-pyra-zole-3-carboxylate (CAS: 866837-96-9, 300 mg, 1.3 mmol) in THF (6.5 mE), under nitrogen atmosphere was cooled down to -78 C. Diisobutylaluminum hydride (1 M in toluene, 2.9 mE, 2.9 mmol) was added dropwise to the solution, and the stirring at -78 C. was continued for 1 hour. Methanol was added, and the reaction mixture was stirred for 30 minutes warming to RT. DCM was added, and the organic phase was washed with water. The organic phase was separated using a phase separator and concentrated under reduced pressure. The titled compound was used as such without any further purification.

The synthetic route of 866837-96-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Akkari, Rhalid; Alvey, Luke Jonathan; Bock, Xavier Marie; Claes, Pieter Isabelle Roger; Cowart, Marlon D.; De Lemos, Elsa; Desroy, Nicolas; Duthion, Beranger; Gfesser, Gregory A.; Gosmini, Romain Luc Marie; Housseman, Christopher Gaetan; Jansen, Koen Karel; Ji, Jianguo; Kym, Philip R.; Lefrancois, Jean-Michel; Mammoliti, Oscar; Menet, Christel Jeanne Marie; Newsome, Gregory John Robert; Palisse, Adeline Marie Elise; Patel, Sachin V; Pizzonero, Mathieu Rafael; Shrestha, Anurupa; Swift, Elizabeth C.; Van der Plas, Steven Emiel; Wang, Xueqing; (454 pag.)US2017/101406; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics