33668-25-6Relevant academic research and scientific papers
A photo-reagent system of benzimidazoline and Ru(bpy)3Cl 2 to promote hexenyl radical cyclization and Dowd-Beckwith ring-expansion of α-halomethyl-substituted benzocyclic 1-alkanones
Hasegawa, Eietsu,Tateyama, Minami,Hoshi, Tsuneaki,Ohta, Taku,Tayama, Eiji,Iwamoto, Hajime,Takizawa, Shin-Ya,Murata, Shigeru
, p. 2776 - 2783 (2014)
A combination of 2-aryl substituted 1,3-dimethyl-benzimidazolines (DMBIHs) and tris(2,2′-bipyridine)ruthenium(II) chloride, Ru(bpy) 3Cl2 was used to promote photoinduced electron-transfer (PET) reactions of α-halomethyl-substituted benzocyclic 1-alkanones. This photo-reagent system stimulates free radical forming, cleavage of both carbon-bromine and carbon-chlorine bonds that are not activated by carbonyl groups. The resulting free radicals undergo 5-exo hexenyl cyclization as well as sequential cyclization and ring-expansion (Dowd-Beckwith) reactions to form radicals that abstract hydrogen atoms from the radical cation of DMBIH to yield the observed products. The results of a study of the effects of substituents located on the 2-aryl ring of DMBIH suggest that steric and hydrogen-bonding interactions influence the nature of the reaction pathways followed by the radical intermediates. PET reactions using an iridium complex and DMBIH were also investigated.
Rapid Enantioselective and Diastereoconvergent Hybrid Organic/Biocatalytic Entry into the Oseltamivir Core
Tiwari, Virendra K.,Powell, Douglas R.,Broussy, Sylvain,Berkowitz, David B.
supporting information, p. 6494 - 6503 (2021/05/06)
A formal synthesis of the antiviral drug (-)-oseltamivir (Tamiflu) has been accomplished starting from m-anisic acid via a dissolving metal or electrochemical Birch reduction. The correct absolute stereochemistry is efficiently set through enzyme-catalyzed carbonyl reduction on the resultant racemic α,β-unsaturated ketone. A screen of a broad ketoreductase (KRED) library identified several that deliver the desired allylic alcohol with nearly perfect facial selectivity at the new center for each antipodal substrate, indicating that the enzyme also is able to completely override inherent diastereomeric bias in the substrate. Conversion is complete, with d-glucose serving as the terminal hydride donor (glucose dehydrogenase). For each resulting diastereomeric secondary alcohol, O/N-interconversion is then efficiently effected either by synfacial [3,3]-sigmatropic allylic imidate rearrangement or by direct, stereoinverting N-Mitsunobu chemistry. Both stereochemical outcomes have been confirmed crystallographically. The α,β-unsaturation is then introduced via an α-phenylselenylation/oxidation/pyrolysis sequence to yield the targeted (S)-N-acyl-protected 5-amino-1,3-cyclohexadiene carboxylates, key advanced intermediates for oseltamivir pioneered by Corey (N-Boc) and Trost (N-phthalamido), respectively.
Phosphinous Acid Platinum Complex as Robust Catalyst for Oxidation: Comparison with Palladium and Mechanistic Investigations
Membrat, Romain,Vasseur, Alexandre,Martinez, Alexandre,Giordano, Laurent,Nuel, Didier
supporting information, p. 5427 - 5434 (2018/10/20)
Secondary phosphine oxides proved to be effective preligands to stabilise a hydroxy-platinum based catalyst that allows the aerobic/anaerobic oxidation of challenging substrates. Kinetic comparisons showed that this system is more efficient and stable than previously reported similar palladium-based catalysts. A neutral platinum dimer bearing bridging hydroxy ligands has been isolated and fully characterised by X-ray diffraction and its involvement in the mechanism has been evidenced by mechanistic studies.
Synthesis of gem-difluorocyclopentane/hexane building blocks
Melnykov, Kostiantyn P.,Nosik, Pavel S.,Kurpil, Bohdan B.,Sibgatulin, Dmitriy A.,Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Grygorenko, Oleksandr O.
, p. 60 - 66 (2017/05/17)
An approach to the preparation of gem-difluorocyclopentane/hexane-derived carboxylic acids and amines is described. Whereas for 3,3-difluoro-substituted cycloalkanones, straightforward deoxofluorination of the corresponding ketoesters led to the target compounds, in the case of 2,2-difluoro isomers, the bypass or alternative routes were necessary.
Biocatalytic synthesis of chiral cyclic γ-oxoesters by sequential C-H hydroxylation, alcohol oxidation and alkene reduction
Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Monti, Daniela,Parmeggiani, Fabio,Pugliese, Andrea,Tentori, Francesca
, p. 5122 - 5130 (2017/11/09)
A three-step biocatalytic procedure is described for the conversion of methyl and ethyl cyclopentene- and cyclohexenecarboxylates into both the enantiomers of the corresponding chiral 3-oxoesters, which are useful building blocks for the synthesis of active pharmaceutical ingredients. The allylic hydroxylation of the starting cycloalkenecarboxylates is carried out by using R. oryzae resting cells entrapped in alginate beads, in acetate buffer solution at 25 °C. The oxidation of the intermediate allylic alcohols to unsaturated ketones, performed by the laccase/TEMPO system, and the ene-reductase mediated hydrogenation of the alkene bond were carried out in the same reaction vessel in a sequential mode at 30 °C. Being entirely biocatalytic, our multistep procedure provides considerable advantages in terms of selectivity and environmental impact over reported chemical methods.
Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)
De Lucca, George V.,Shi, Qing,Liu, Qingjie,Batt, Douglas G.,Beaudoin Bertrand, Myra,Rampulla, Rick,Mathur, Arvind,Discenza, Lorell,D'Arienzo, Celia,Dai, Jun,Obermeier, Mary,Vickery, Rodney,Zhang, Yingru,Yang, Zheng,Marathe, Punit,Tebben, Andrew J.,Muckelbauer, Jodi K.,Chang, Chiehying J.,Zhang, Huiping,Gillooly, Kathleen,Taylor, Tracy,Pattoli, Mark A.,Skala, Stacey,Kukral, Daniel W.,McIntyre, Kim W.,Salter-Cid, Luisa,Fura, Aberra,Burke, James R.,Barrish, Joel C.,Carter, Percy H.,Tino, Joseph A.
, p. 7915 - 7935 (2016/10/12)
Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.
9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors
Zimmermann, Kurt,Sang, Xiaopeng,Mastalerz, Harold A.,Johnson, Walter L.,Zhang, Guifen,Liu, Qingjie,Batt, Douglas,Lombardo, Louis J.,Vyas, Dinesh,Trainor, George L.,Tokarski, John S.,Lorenzi, Matthew V.,You, Dan,Gottardis, Marco M.,Lippy, Jonathan,Khan, Javed,Sack, John S.,Purandare, Ashok V.
, p. 2809 - 2812 (2015/06/08)
The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.
IRAK INHIBITORS AND USES THEREOF
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Paragraph 00284-00285, (2014/02/15)
The present invention provides arylo-fused thienopyrimidine compounds, compositions thereof, and methods of using the same.
FLT3 INHIBITORS AND USES THEREOF
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Paragraph 00353; 00356, (2014/12/12)
The present invention provides methods of using compounds of formula I: or compositions thereof for the inhibition of FLT3, and the treatment of FLT3-mediated disorders.
Photoinduced electron transfer promoted radical ring expansion and cyclization reactions of α-(ω-carboxyalkyl) β-keto esters
Nishikawa, Keisuke,Ando, Tomoki,Maeda, Kousuke,Morita, Toshio,Yoshimi, Yasuharu
supporting information, p. 636 - 638 (2013/04/10)
Photoinduced electron transfer (PET) promoted decarboxylation of α-(ω-carboxyalkyl) β-keto esters undergoes radical ring expansion and cyclization reactions. This mild and environmentally friendly method can provide one-carbon expanded γ-keto esters and b
