78686-86-9Relevant articles and documents
Synthesis of [14C]- and [13C6]-labeled potent HIV non-nucleoside reverse transcriptase inhibitor
Latli, Bachir,Hrapchak, Matt,Busacca, Carl A.,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
, p. 84 - 90 (2009)
5,11-Dihydro-11-ethyl-5-methyl-8-{2-{(1-oxido-4-quinolinyl)oxy}ethyl} -6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one, (1), labeled with carbon-14 in the quinoline-benzene ring, in one of the pyridine rings of the dipyridodiazepinone tricyclic moiety, and in the side chain, was prepared in three different syntheses with specific activities ranging from 44 to 47 mCi/mmol (1.63-1.75 GBq/mmol). In the first synthesis, 5,11-dihydro-11-ethyl-8- (2-hydroxyethyl)-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4] diazepin-6-one (2) was coupled to 4-hydroxyquinoline, [benzene- 14C(U)]-, using Mitsunobu's reaction conditions, followed by the oxidation of the quinoline nitrogen with 3-chloroperoxybenzoic acid to give ([14C]-(1a)) in 43% radiochemical yield. Second, 3-amino-2- chloropyridine, [2,6-14C]-, was used to prepare 8-bromo-5,11-dihydro- 11-ethyl-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (8), and then Stille coupled to allyl(tributyl)tin followed by ozonolysis of the terminal double bond and in situ reduction of the resulting aldehyde to alcohol (10). Mitsunobu etherification and oxidation as seen before gave ([ 14C]-(1b)) in eight steps and in 11% radiochemical yield. Finally, carbon-14 potassium cyanide was used to prepare isopropyl cyanoacetate (12), which was used to transform bromide (8) to labeled aryl acetic acid (13) under palladium catalysis. Trihydroborane reduction of the acid gave alcohol (14) labeled in the side chain, which was used as described above to prepare ([ 14C]-(1c)) in 4.3% radiochemical yield. The radiochemical purities of these compounds were determined by radio-HPLC and radio-TLC to be more than 98%. To prepare [13C6]-(1), [13C 6]-4-hydroxyquinoline was prepared from [13C 6]-aniline and then coupled to (2) and oxidized as seen before. Copyright
MITOCHONDRIAL ALDEHYDE DEHYDROGENASE 2 (ALDH2) BINDING POLYCYCLIC AMIDES AND THEIR USE FOR THE TREATMENT OF CANCER
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Page/Page column 148, (2015/09/28)
The present invention provides compounds of formula I that bind to mitochondrial aldehyde dehydrogenase-2 (ALDH2), and methods of using said compounds to treat patients with i.a. cancer, Fanconi anemia and alcohol-related disorders. [Formula should be ins
Iridium-catalyzed C-H borylation of heteroarenes: Scope, regioselectivity, application to late-stage functionalization, and mechanism
Larsen, Matthew A.,Hartwig, John F.
supporting information, p. 4287 - 4299 (2014/04/03)
A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were found to be amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodology for the synthesis of complex heteroaryl structures. Application of this methodology to the synthesis and late-stage functionalization of biologically active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen.
