131195-91-0Relevant academic research and scientific papers
Preparation method of ortho-amino trifluoroacetophenone and derivatives thereof
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Paragraph 0041; 0045-0048, (2021/11/19)
The invention relates to the field of organic synthesis, in particular to a preparation method of ortho-amino trifluoroacetophenone and derivatives thereof. The preparation of ortho-amino trifluoroacetophenone comprises three steps of amino protection, trifluoroacetylation and deprotection, the overall reaction condition is mild, the yield is high, and the method is suitable for large-scale production. In addition, on the basis of the preparation, substitution is carried out after amino diazotization, the ortho-amino trifluoroacetophenone derivative is further prepared, and the industrial application prospect is good.
Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
supporting information, p. 417 - 428 (2019/02/14)
Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
Efficient Electrocatalysis for the Preparation of (Hetero)aryl Chlorides and Vinyl Chloride with 1,2-Dichloroethane
Liang, Yujie,Lin, Fengguirong,Adeli, Yeerlan,Jin, Rui,Jiao, Ning
supporting information, p. 4566 - 4570 (2019/02/14)
Although the application of 1,2-dichloroethane (DCE) as a chlorinating reagent in organic synthesis with the concomitant release of vinyl chloride as a useful byproduct is a fantastic idea, it still presents a tremendous challenge and has not yet been achieved because of the harsh dehydrochlorination conditions and the sluggish C?H chlorination process. Here we report a bifunctional electrocatalysis strategy for the catalytic dehydrochlorination of DCE at the cathode simultaneously with anodic oxidative aromatic chlorination using the released HCl as the chloride source for the efficient synthesis of value-added (hetero)aryl chlorides. The mildness and practicality of the protocol was further demonstrated by the efficient late-stage chlorination of bioactive molecules.
A Visible Light-Mediated Regioselective Halogenation of Anilides and Quinolines by Using a Heterogeneous Cu-MnO Catalyst
Singh, Harshvardhan,Sen, Chiranjit,Sahoo, Tapan,Ghosh, Subhash Chandra
, p. 4748 - 4753 (2018/09/06)
A simple and practical heterogeneous Cu-MnO catalyzed regioselective halogenation of anilides and quinolines under irradiation with household 40 W incandescent lamp was developed. This method uses a recyclable Cu-MnO catalyst, acetonitrile as an industrially friendly solvent, and economic N-halo succinimides as a halogenating source. The reaction is scalable and well tolerated with a broad range of functional groups.
Discovery of atrop fixed alkoxy-aminobenzhydrol derivatives: Novel, highly potent and orally efficacious squalene synthase inhibitors
Ichikawa, Masanori,Yokomizo, Aki,Itoh, Masao,Haginoya, Noriyasu,Sugita, Kazuyuki,Usui, Hiroyuki,Terayama, Koji,Kanda, Akira
experimental part, p. 5207 - 5224 (2011/10/08)
We have recently reported the discovery of the new benzhydrol template, which has a highly potent inhibitory activity for squalene synthase, as typified by compound 1 (SSI IC50 = 0.85 nM). However, it was composed of a pair of easy rotatable at
Synthesis and evaluation of analogs of Efavirenz (SUSTIVA(TM)) as HIV-1 reverse transcriptase inhibitors
Patel, Mona,Ko, Soo S.,McHugh Jr., Robert J.,Markwalder, Jay A.,Srivastava, Anurag S.,Cordova, Beverly C.,Klabe, Ronald M.,Erickson-Viitanen, Susan,Trainor, George L.,Seitz, Steven P.
, p. 2805 - 2810 (2007/10/03)
Efavirenz (SUSTIVA(TM)) is a potent non-nucleoside reverse transcriptase inhibitor. Due to the observation of breakthrough mutations of the reverse transcriptase enzyme during Efavirenz therapy, we sought to develop an optimized second generation series. To that end, SAR of the substituents on the aromatic ring was undertaken and the results are summarized here. The 5,6-difluoro (4f) and the 6-methoxy (4m) substituted benzoxazinones were determined to be equipotent, and as a result such substitution patterns will be incorporated in second generation scaffolds.
