- Regioselective electrophilic formylation - 3-substituted thiophenes as a case study
-
A variety of methods for regioselective formylation have been examined and exemplified with 3-methylthiophene. Optimal yields and regioselectivity for 2-formylation were obtained with N-formylpyrrolidine (11:1) although up to a 46:1 ratio could be obtained with MeOCHCl2:TiCl4, albeit in lower yield. Optimal 5-formylation (1:1.5) was obtained when using N- formylindoline:(COCl)2. (C) 2000 Elsevier Science Ltd.
- Meth-Cohn, Otto,Ashton, Mark
-
-
Read Online
- Synthesis and optical/electrochemical properties of meso-5,10,15,20-tetrathienyl substituted porphyrins and their metal complexes
-
Two kinds of meso-5,10,15,20-tetrathienyl substituted porphyrin compounds, meso-5,10,15,20-tetra(2-thienyl)porphyrin (H2TTP), meso-5,10,15,20-tetra(3-methyl-2-thienyl)porphyrin [H2T(3-M)TP] and their metal complexes were synthesized and characterized by IR, 1H NMR. UV-visible absorption spectra, fluorescence spectra, photoluminescence spectra and the cyclic voltammograms of the synthesized porphyrins and metalloporphyrins. Optical properties reveal that zinc porphyrin possesses intensive fluorescence emission, whereas cobalt(II) and copper(II) porphyrins exhibit no fluorescence emission. When the complexation of H2TTP and H2T(3-M)TP with metal ions occur, the electrochemical band-gaps (Eg) increase meanwhile the ELUMO shows smaller change than that of the EHOMO. The values of ionization potential, electronic affinity, HOMO energy level (EHOMO) and LUMO energy level (ELUMO) of the synthesized porphyrins and metalloporphyrins were also given in the paper.
- Zhou, Yong,Liu, Fude,Wu, Haiyan,Qu, Boyang,Duan, Lijie
-
-
Read Online
- Systematic structure-activity relationship (SAR) exploration of diarylmethane backbone and discovery of a highly potent novel uric acid transporter 1 (URAT1) inhibitor
-
In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a-1x and 1ha-1hi) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC50) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h, which was 200-and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC50 = 0.035 μM against human URAT1 for 1h vs. 7.18 μM and 0.28 μM for lesinurad and benzbromarone, respectively). Compound 1h is the most potent URAT1 inhibitor discovered in our laboratories so far and also comparable to the most potent ones currently under development in clinical trials. The present study demonstrates that the diarylmethane backbone represents a very promising molecular scaffold for the design of potent URAT1 inhibitors.
- Cai, Wenqing,Wu, Jingwei,Liu, Wei,Xie, Yafei,Liu, Yuqiang,Zhang, Shuo,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
-
-
- Palladium-catalyzed C-H formylation of electron-rich heteroarenes through radical dichloromethylation
-
A novel palladium-catalyzed C-H formylation of electron-rich N-, O-, and S-containing heteroarenes has been developed. The key to success is that the commercially available BrCHCl2 was used as a stoichiometric carbonyl source. Mechanistic investigations indicated that different from the known Reimer-Tiemann reaction, this net C-H formylation proceeded through an electrophilc radical-type path.
- Bao, Yan,Wang, Jian-Yong,Zhang, Ya-Xuan,Li, Yan,Wang, Xi-Sheng
-
supporting information
p. 3147 - 3150
(2018/07/13)
-
- Chemoselective Reduction of Sterically Demanding N,N-Diisopropylamides to Aldehydes
-
A sequential one-pot process for chemoselectively reducing sterically demanding N,N-diisopropylamides to aldehydes has been developed. In this reaction, amides are activated with EtOTf to form imidates, which are reduced with LiAlH(OR)3 [R = t-Bu, Et] to give aldehydes by hydrolysis of the resulting hemiaminals. The non-nucleophilic base 2,6-DTBMP remarkably improves reaction efficiency. The combination of EtOTf/2,6-DTBMP and LiAlH(O-t-Bu)3 was found to be optimal for reducing alkyl, alkenyl, alkynyl, and 2-monosubstituted aryl N,N-diisopropylamides. In contrast, EtOTf and LiAlH(OEt)3 in the absence of base were found to be optimal for reducing extremely sterically demanding 2,6-disubstituted N,N-diisopropylbenzamides. The reaction tolerates various reducible functional groups, including aldehyde and ketone. 1H NMR studies confirmed the formation of imidates stable in water. The synthetic usefulness of this methodology was demonstrated with N,N-diisopropylamide-directed ortho-metalation and C-H bond activation.
- Xiao, Peihong,Tang, Zhixing,Wang, Kai,Chen, Hua,Guo, Qianyou,Chu, Yang,Gao, Lu,Song, Zhenlei
-
p. 1687 - 1700
(2018/02/23)
-
- Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases
-
There is interest in developing potent, selective, and cell-permeable inhibitors of human ferrous iron and 2-oxoglutarate (2OG) oxygenases for use in functional and target validation studies. The 3-component Betti reaction enables efficient one-step C-7 functionalisation of modified 8-hydroxyquinolines (8HQs) to produce cell-active inhibitors of KDM4 histone demethylases and other 2OG oxygenases; the work exemplifies how a template-based metallo-enzyme inhibitor approach can be used to give biologically active compounds.
- Thinnes,Tumber,Yapp,Scozzafava,Yeh,Chan,Tran,Hsu,Tarhonskaya,Walport,Wilkins,Martinez,Müller,Pugh,Ratcliffe,Brennan,Kawamura,Schofield
-
supporting information
p. 15458 - 15461
(2015/10/20)
-
- Synthesis of N-(Methoxycarbonylthienylmethyl)thioureas and evaluation of their interaction with inducible and neuronal nitric oxide synthase
-
Two isomeric N-(memoxycarbonylmienylmemyl)mioureas were synthesised by a sequence of radical bromination of methylthiophenecarboxylic esters, substitution with trifluoroacetamide anion, deprotection, formation of the corresponding isothiocyanates and addition of ammonia. The interaction of these new thiophene-based thioureas with inducible and neuronal nitric oxide synthase was evaluauted. These novel thienylmethyl- thioureas stimulated the activity of inducible Nitric Oxide Synthase (iNOS).
- Suaifan, Ghadeer A.R.Y.,Goodyer, Claire L.M.,Threadgill, Michael D.
-
experimental part
p. 3121 - 3134
(2010/09/04)
-
- Chiral helicenoid diarylethene with large change in specific optical rotation by photochromism
-
A diarylethene possessing one [4]thiaheterohelicene and one benzothiophene, the latter with a chiral methoxymethoxyethyl group on its C-3 position, was proved to work as a switch of specific optical rotation at a wavelength at which both colored and colorless forms have no absorption in solution. The difference of the specific optical rotation was 1300° between the open form and the photostationary state. The specific optical rotation of one of the isolated optically active major colored forms was -4680°. The conversion to the colored form was 64%, and the diastereomeric excess of photocyclization was 47%.
- Okuyama, Tomoyuki,Tani, Yutaka,Miyake, Kentaro,Yokoyama, Yasushi
-
p. 1634 - 1638
(2007/10/03)
-
- Highly selective 5-substitution of 3-methylthiophene via directed lithiation
-
(Chemical Equation Presented) Lithiation of 3-methylthiophene with lithium 2,2,6,6-tetramethylpiperidide (LiTMP) is highly selective at the 5-position, and reaction with a range of electrophiles gives high yields of the corresponding 2,4-disubstituted thiophenes, even when unhindered electrophiles are used.
- Smith, Keith,Barratt, Mark Lewis
-
p. 1031 - 1034
(2008/02/04)
-
- Ramoplanin derivatives possessing antibacterial activity
-
Novel ramoplanin derivatives are disclosed. These ramoplanin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against gram positive bacteria, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
- -
-
Page/Page column 55
(2010/11/23)
-
- Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: Potent human histamine H4 antagonists
-
Three series of H4 receptor ligands,- derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H 4 receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4 and 5-positions led to increased activity in a [3H]histamine radiolabeled ligand competitive binding assay. In vitro metabolism and initial pharmacokinetic studies were performed on selected compounds leading to the identification of indole 8 and benzimidazole 40 as potent H4 antagonists with the potential for further development. In addition, both 8 and 40 demonstrated efficacy in in vitro mast cell and eosinophil chemotaxis assays.
- Venable, Jennifer D.,Cai, Hui,Chai, Wenying,Dvorak, Curt A.,Grice, Cheryl A.,Jablonowski, Jill A.,Shah, Chandra R.,Kwok, Annette K.,Ly, Kiev S.,Pio, Barbara,Wei, Jianmei,Desai, Pragnya J.,Jiang, Wen,Nguyen, Steven,Ling, Ping,Wilson, Sandy J.,Dunford, Paul J.,Thurmond, Robin L.,Lovenberg, Timothy W.,Karlsson, Lars,Carruthers, Nicholas I.,Edwards, James P.
-
p. 8289 - 8298
(2007/10/03)
-
- 4-Amino-thieno[3,2-c]pyridine-7-carboxylic acid amides
-
Disclosed are novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides, and their pharmaceutically acceptable salts and esters, that are selective inhibitors of KDR and/or FGFR kinases. These compounds and their pharmaceutically acceptable salts are anti-proliferative agents useful in the treatment or control of solid tumors, in particular solid cancerous tumors of the breast, colon, lung and prostate. Also disclosed are pharmaceutical compositions containing these compounds and methods of treating cancer using these compounds.
- -
-
Page/Page column 10
(2010/02/14)
-
- Heterocyclic compounds
-
Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H4 receptor, including allergic rhinitis.
- -
-
Page/Page column 12
(2010/02/05)
-
- STUDIES TOWARD ALKYLTHIOPHENE-2-CARBOXALDEHYDES. REDUCTION OF 3-ALKENYLTHIOPHENES WITH TRIETHYLSILANE/TRIFLUOROACETIC ACID. REGIOSELECTIVTY IN FORMYLATION REACTIONS OF ALKYLTHIOPHENES
-
Reduction of 2- or 3-alkenylthiophenes with Et3SiH/CF3CO2H in CH2Cl2 gives the corresponding 2- or 3-alkylthiophene in >90percent isolated yield.The regioselectivity of various Vilsmeier formylations of 3-alkylthiophenes was found to be a function of increasing steric bulk in the 3-alkyl substituent and in the Vilsmeier reagent.The regioselectivty of formylations of 3-alkylthiophenes by initial lithiation with butyllithium in ether followed quenching with DMF is independent of the presence or absence of TMEDA.
- Detty, Michael R.,Hays, David S.
-
p. 925 - 938
(2007/10/02)
-
- Process for production of 2-thiophene aldehydes
-
There is disclosed a process for the production of 2-thiophene aldehydes, in which the 2-thiophene aldehydes are obtained by the formylation of thiophene or derivatives thereof with formamides and phosgene.
- -
-
-
- A Thiophene Analogue of Praziquantel, and Related Systems, by Intramolecular Cyclisation of Acyliminium Salts
-
N--succinimide (7a) and -glutarimide (7b) on reduction with sodium borohydride in methanol at -10 deg C yield the respective hydroxylactams which on treatment with formic acid cyclise via the intermediate acyliminium ions to 4,5,9,9a-tetrahydropyrrolothienopyridin-7-one (9a) and 4,5,8,9,10,10a-hexahydropyridothienopyridin-7-one (9b) respectively.In a similar manner, 4-cyclohexylcarbonyl-1-piperazine-2,6-dione (11) is converted into the thiophene isostere (2) of praziquantel (1).Likewise, formic acid induced cyclisations of the hydroxylactams derived from N-- (16) and N-succinimide (19) furnish 5,6,10,10a-tetrahydropyrrolothienothiazepin-8(9H)-one (18) and 5,6,10,10a-tetrahydropyrrolothienothiazepin-8(9H)-one (21), respectively.
- Meth-Cohn, Otto,Vij, Rup Rani,Smalley, Robert K.,Bass, Robert J.
-
p. 1001 - 1018
(2007/10/02)
-
- Lithiation of Heterocycles Directed by α-Amino Alkoxides
-
The addition of heterocyclic aromatic aldehydes to certain lithium dialkylamides gave α-amino alkoxides that were ring-lithiated with butyllithium.Alkylation and hydrolysis provided ring-substituted heterocyclic aromatic aldehydes via a one-pot reaction.The metalation of α-amino alkoxides derived from thiophenecarboxaldehydes, furaldehydes, N-methylpyrrolecarboxaldehydes, and indolecarboxaldehydes was examined.The regioselectivity of the lithiation, was dependent on the heterocycle, the amine component of the α-amino alkoxide, and the metalation conditions.A novel N-methyl metalation of α-amino alkoxides derived from N-methylpyrrole-2-carboxaldehyde and N-methylindole-2-carboxaldehyde was achieved when N,N,N'-trimethylethylenediamine was used as the amine component for in situ formation of the α-amino alkoxides.The novel directed N-methyl lithiations are attributed to an intramolecular TMEDA-like assisted metalation.
- Comins, Daniel L.,Killpack, Michael O.
-
p. 104 - 109
(2007/10/02)
-
- Processes for making 3-methylthiophene-2-carboxaldehyde and intermediates therefor
-
Processes for preparing isomerically pure 3-methylthiophene-2-carboxaldehyde, an intermediate for synthesis of anthelmintic agents, by reaction of mercaptoacetaldehyde or the dimer, or a polymer thereof, or a dialkylacetal thereof in the presence of a base with (1) methyl vinyl ketone or an alpha- or beta-oxidized derivative of methyl vinyl ketone to form a 3-oxobutylmercaptoacetaldehyde or dialkyl acetal thereof, or an alpha- or beta-substituted derivative thereof which is then converted to 3-methylthiophene-2-carboxaldehyde via appropriate steps including, if necessary, treatment with acid, followed, if necessary, by enamine catalyzed cyclization and, in the case of using methyl vinyl ketone as reactant, a dehydrogenation step; or (2) 3-butyn-2-one to produce a mixture of isomeric 3-oxobut-1-enylmercaptoacetaldehyde or dialkyl acetals thereof which is cyclized to 3-methylthiophene-2-carboxaldehyde. A further aspect of this invention is an improved process for making dialkyl acetals of 2-mercaptoacetaldehyde which comprises reacting an alkyl vinyl ether with sulfur chloride to produce a bis(2-chloro-2-alkoxy ethyl)disulfide which is then treated with an alcohol to afford a bis(2,2-dialkoxyethyl)disulfide which is reduced under alkaline conditions to 2-mercaptoethyl acetaldehyde alkali metal salt which can be alkylated to a thioether, a valuable intermediate.
- -
-
-
