717-94-2Relevant academic research and scientific papers
Cobalt-catalyzed cross-coupling reactions of aryl- And alkylaluminum derivatives with (hetero)aryl and alkyl bromides
Dilauro, Giuseppe,Messa, Francesco,Bona, Fabio,Perrone, Serena,Salomone, Antonio
supporting information, p. 10564 - 10567 (2021/10/19)
A simple cobalt complex, such as Co(phen)Cl2, turned out to be a highly efficient and cheap precatalyst for a host of cross-coupling reactions involving aromatic and aliphatic organoaluminum reagents with aryl, heteroaryl and alkyl bromides. New C(sp2)-C(sp2) and C(sp2)-C(sp3) bonds were formed in good to excellent yields and with high chemoselectivity, under mild reaction conditions.
Method for synthesizing phenylpropionic acid compounds through heterogeneous palladium metal catalysis
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Paragraph 0084-0091, (2021/04/21)
The invention discloses a method for synthesizing phenylpropionic acid compounds by heterogeneous catalysis. The method comprises the following steps: sequentially adding Pd@POL, toluene, styrene, formic acid and acetic anhydride into a reaction flask, stirring the reaction mixture at 80 DEG C to react, cooling the reaction solution to room temperature after the reaction is finished, diluting with dichloromethane, and transferring the solution into a separating funnel, washing with a sodium hydroxide solution, acidifying the water layer with a hydrochloric acid aqueous solution, extracting with dichloromethane, merging organic phases, drying with anhydrous sodium sulfate, and carrying out vacuum concentration to obtain the phenylpropionic acid compound. The method can remove heavy metal residues, is green and environment-friendly, is simple to operate and easy to implement, and the prepared phenylpropionic acid compound has a good application prospect.
Method for preparing AZD4547, intermediate and preparation method of intermediate
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Paragraph 0084-0089, (2020/05/14)
The invention provides a method for preparing AZD-4547. The method comprises the following steps: (1) preparing a first intermediate 2-cyano-5-(3, 5-dimethoxyphenyl)-3-oxoethyl valerate; (2) preparinga second intermediate 5-[2-(3, 5-dimethoxyphenyl) ethyl]-1H-pyrazole-3-amine by taking the first intermediate as a raw material; and (3) in an alkali-containing organic solvent, carrying out a reaction on a third intermediate 4-((3S, 5R)-3, 5-dimethylpiperazinyl-1-yl) benzoyl chloride and the second intermediate to prepare the AZD-4547. The method has the advantages of accessible raw materials, simple technique, mild reaction conditions, convenient operation, high yield and low cost and can easily implement industrial production. The invention also provides an intermediate 2-cyano-5-(3, 5-dimethoxyphenyl)-3-oxoethyl valerate for preparing AZD-4547 and a preparation method thereof.
New and convergent synthesis of AZD 4547
Bu, Lehao,Chen, Wenxin,Gao, Lei,Mao, Yongjun,Sun, Cong,Wang, Han
, p. 276 - 282 (2020/06/10)
A practical and convergent synthetic route of AZD 4547 was developed successfully. The intermediate 5-(3,5-dimethoxyphenylethyl)-1H-pyrazol-3-amine (7) was prepared from 3,5-dimethoxybenzaldehyde through 6 simple steps in 52.3% yield. Another intermediate 4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzoic acid (14) was synthesized from ethyl 4-fluorobenzoate and (2R,6S)-2,6-dimethylpiperazine in 62% yield over 2 steps. Finally, AZD 4547 was obtained from 7 and 14 in 73% yield and 99.1% purity. Purification methods of the intermediates and the final product involved in the route were developed.
Design, synthesis and biological evaluation of novel 1H-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors viafragment-based virtual screening
Liu, Jian,Wen, Yu,Gao, Lina,Gao, Liang,He, Fengjun,Zhou, Jingxian,Wang, Junwei,Dai, Rupeng,Chen, Xiaojing,Kang, Di,Hu, Lihong
, p. 72 - 84 (2019/11/14)
Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.
ACYL HYDRAZONE LINKERS, METHODS AND USES THEREOF
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Paragraph 00228, (2019/07/04)
The present application is directed to compounds of Formula (I)-(VI): (I), (II), (III), (IV), (V) (VI), (VII) and (VIII), compositions comprising these compounds and their uses, for example as medicaments and/or diagnostics.
Synthesis and Biological Evaluation of Tripartin, a Putative KDM4 Natural Product Inhibitor, and 1-Dichloromethylinden-1-ol Analogues
Guillade, Lucía,Sarno, Federica,Tarhonskaya, Hanna,Nebbioso, Angela,Alvarez, Susana,Kawamura, Akane,Schofield, Christopher J.,Altucci, Lucia,de Lera, ángel R.
supporting information, p. 1949 - 1956 (2018/09/14)
The natural product tripartin has been reported to inhibit the N-methyl-lysine histone demethylase KDM4A. A synthesis of tripartin starting from 3,5-dimethoxyphenylacrylic acid was developed, and the enantiomers were separated by chiral HPLC. We observed
Synthesis of C4-C5 cycloalkyl-fused and C6-modified chromans via ortho-quinone methides
Tangdenpaisal, Kassrin,Chuayboonsong, Kanokpish,Sukjarean, Patchaya,Katesampao, Varisa,Noiphrom, Nok,Ruchirawat, Somsak,Ploypradith, Poonsakdi
, p. 1050 - 1064 (2015/03/31)
Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-cycloalkyl-fused and 6-modified chromans could be prepared via ortho-quinone methides (o-QMs)/hetero-Diels-Alder (HDA) reactions of the appropriate precursors.
First synthesis of dopamine and rotigotin analogue 2-amino-6,8-dimethoxy-1, 2,3,4-tetrahydronaphthalene
Yilmaz, Süleyman,G?ksu, Süleyman
, p. 1058 - 1065 (2014/04/03)
The title compound was synthesized starting from 3-(3,5-dimethoxyphenyl) acrylic acid in 11 steps with 30% total yield. The reaction sequence hydrogenation of acrylic acid, reduction of acid to alcohol derivative with LiAlH4, reaction of alcohol with CBr4/PPh3, substitution reaction of alkyl halide to nitrile derivative with NaCN, hydrolysis of nitrile with NaOH, cyclization reaction of acid with PPA to give 1-tetralone, α-carboxylation of tetralone with Me2CO 3 in the presence of NaH, reduction of ketone group with Et 3SiH, hydrolysis of ester, Curtius rearrangement of acid with diphenylphosphoryl azide followed by conversion to carbamate, and finally hydrogenolysis of carbamate afforded 2-amino-6,8-dimethoxy-1,2,3,4- tetrahydronaphthalene hydrogen chloride salt.
Synthesis and antitumor activity evaluation of 2-arylisoquinoline-1,3(2H, 4H)-diones in vitro and in vivo
Kang, Bo-Rui,Wang, Juan,Li, Huan,Li, Yan,Mei, Qi-Bing,Zhang, San-Qi
, p. 1340 - 1349 (2014/03/21)
Six 2-(2-acylaminobenzothiazol-6-yl)isoquinoline-1,3(2H,4H)-diones (1a-1f) and five 2-arylisoquinoline-1,3(2H,4H)-diones (1g-1k) were synthesized by refluxing homophthalic anhydrides with 2-acylaminobenzothiazolyl-6-amine or substituted aniline in glacial acetic acid. The cytotoxic activities of 1a-1k were evaluated via MTT method against A431, A549, and PC3. Compound 1b relatively displayed a higher cytotoxic activity than the others. The antitumor effect of 1b were evaluated in established nude mice PANC-1 xenograft model. The results suggest that compound 1b could potentially inhibit tumor growth.
