34259-99-9Relevant academic research and scientific papers
Synthesis of thiazole compounds via lithiation: An unexpected rearrangement
Ross Kelly,Lang, Fengrui
, p. 9293 - 9296 (1995)
A novel rearrangement was discovered during an investigation of the lithium-bromine exchange reactions of bromothiazole derivatives and their subsequent reactions with various electrophiles.
Process Development of a Second Generation β-Amyloid-Cleaving Enzyme Inhibitor - Improving the Robustness of a Halogen-Metal Exchange Using Continuous Stirred-Tank Reactors
Li, Bryan,Barnhart, Richard W.,Dion, Amelie,Guinness, Steven,Happe, Alan,Hayward, Cheryl M.,Kohrt, Jeffrey,Makowski, Teresa,Maloney, Mark,Nelson, Jade D.,Nematalla, Asaad,McWilliams, J. Christopher,Peng, Zhihui,Raggon, Jeffrey,Sagal, John,Weisenburger, Gerald A.,Bao, Denghui,Gonzalez, Miguel,Lu, Jiangping,McLaws, Mark D.,Tao, Jian,Wu, Baolin
, p. 1440 - 1453 (2021/06/21)
Process development for the synthesis of a second generation β-amyloid-cleaving enzyme (BACE1) inhibitor (1) is described. The lithiothiazole addition to the isoxazolene (5) under batch conditions was not scalable because of reaction gelling and anion instability. A continuous stirred-tank reactor flow process was developed and successfully executed on the 70 kg scale in multiple runs. In a head-to-head comparison between the continuous and batch processes, the former was clearly superior as it gave a higher yield (80 vs 63%) of the adduct (4) and better reaction control for handling the unstable lithiothiazole as a reaction intermediate. Subsequently, 4 underwent Pd-catalyzed amination with t-butyl carbamate, reductive cleavage of the N-O bond, thioamidine cyclization, and deprotection of the Boc group to provide hydropyranothiazine 2. The synthesis of 1 was completed by amidation with 5-(difluoromethoxy)picolinic acid and the successive deprotection of the benzamide group with either Silicycle-diamine or l-lysine.
An Approach to Nonsymmetric Bis(tertiary phosphine oxides) Comprising Heterocyclic Fragments via the Pd-Catalyzed Phosphorylation
Zakirova, Gladis G.,Mladentsev, Dmitrii Yu.,Borisova, Nataliya N.
supporting information, p. 1833 - 1837 (2020/09/21)
Nonsymmetric tertiary phosphine oxides with different five- and six-membered heterocyclic fragments such as pyridine, 2,2′-bipyridine, 1,10-phenantroline, quinoline, imidazole, and thiazole were synthesized in good yields via the successive introduction of phosphine oxide groups into the initial dihalogenated heterocycles by means of Pd-catalyzed phosphorylation reaction. The synthesis of pyridine-type compounds is hindered by competing double coupling, while for five-membered heterocycles the principal difficulty is the dehalogenation. Both side processes were successfully suppressed by the use of an excess of a dihalide (which can be easily recovered during the product purification step), proper phosphine ligand for palladium, and nonpolar solvent such as toluene.
Novel 4,8-benzobisthiazole copolymers and their field-effect transistor and photovoltaic applications
Conboy, Gary,Taylor, Rupert G. D.,Findlay, Neil J.,Kanibolotsky, Alexander L.,Inigo, Anto R.,Ghosh, Sanjay S.,Ebenhoch, Bernd,Krishnan Jagadamma, Lethy,Thalluri, Gopala Krishna V. V.,Sajjad, Muhammad T.,Samuel, Ifor D. W.,Skabara, Peter J.
supporting information, p. 11927 - 11936 (2017/11/30)
A series of copolymers containing the benzo[1,2-d:4,5-d′]bis(thiazole) (BBT) unit has been designed and synthesised with bisthienyl-diketopyrrolopyrrole (DPP), dithienopyrrole (DTP), benzothiadiazole (BT), benzodithiophene (BDT) or 4,4′-dialkoxybithiazole (BTz) comonomers. The resulting polymers possess a conjugation pathway that is orthogonal to the more usual substitution pathway through the 2,6-positions of the BBT unit, facilitating intramolecular non-covalent interactions between strategically placed heteroatoms of neighbouring monomer units. Such interactions enable a control over the degree of planarity through altering their number and strength, in turn allowing for tuning of the band gap. The resulting 4,8-BBT materials gave enhanced mobility in p-type organic field-effect transistors of up to 2.16 × 10-2 cm2 V-1 s-1 for pDPP2ThBBT and good solar cell performance of up to 4.45% power conversion efficiency for pBT2ThBBT.
Synthesis of Brominated Thiazoles via Sequential Bromination-Debromination Methods
Uzelac, Eric J.,Rasmussen, Seth C.
, p. 5947 - 5951 (2017/06/07)
The synthesis of the full family of bromothiazoles has been revisited in order to update and optimize their production. The species reported include 2-bromothiazole, 4-bromothiazole, 5-bromothiazole, 2,4-dibromothiazole, 2,5-dibromothiazole, 4,5-dibromothiazole, and 2,4,5-tribromothiazole, the majority of which are produced via sequential bromination and debromination steps. This complete family can now be produced without the use of elemental bromine, and the presented methods have allowed the physical and NMR spectroscopic characterization of the full family to be reported for the first time.
Substituted propiolic acid amides and their use for producing drugs
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Page/Page column 44, (2008/12/04)
The present invention relates to substituted propiolic acid amides, methods for the production thereof, medicaments containing these compounds and the use thereof for producing medicaments.
Halogenated 2′-chlorobithiazoles via Pd-catalyzed cross-coupling reactions
Stanetty, Peter,Schnuerch, Michael,Mihovilovic, Marko D.
, p. 3754 - 3761 (2007/10/03)
Halogenated bithiazoles allow facile further functionalization and are, therefore, suitable intermediates for the synthesis of compounds with interesting biological activity or material science properties. The applicability of three coupling methods (Negi
Compounds and compositions as inhibitors of receptor tyrosine kinase activity
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Page/Page column 16-18, (2010/02/11)
The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with cSRC, Lck, FGFR3, Flt3, TrkB, Bmx, and/or PFGFRα kinase
Azoles. Part 8. Metallation and Bromine -> Lithium Exchange Reactions of Polyhalogenothiazoles
Athmani, Salah,Bruce, Andrew,Iddon, Brian
, p. 215 - 219 (2007/10/02)
2,4-Dichloro- and 2,4-dibromo-thiazole were deprotonated at position-5 with LiN(iPr)2 in THF at -78 deg C and the resulting lithium compound was quenched with various reagents, to yield various trisubstituted thiazoles. 2,5-Dibromo-4-chlorothiazole reacted with n-butyllithium in THF at -78 deg C at position-5 and the resulting lithium derivative gave 2-bromo-4-chloro-5-substituted thiazoles when quenched with the appropriate reagent.Both the 2- and 5-bromine-atoms were reactive in diethyl ether. 2,5-Dibromothiazole failed to deprotonate at position-4 under various reaction conditions, whereas treatment of 2,4,5-tribromothiazole with 1 mole equivalent of n-butyllithium in THF at -90 deg C, followed by addition of dimethyl disulfide after 30 min, gave a high yield of the 2,5-bis(methylthio)-compound.The tribromo-compound was also treated with 1 mole equivalent of n-butyllithium or methyllithium under various reaction conditions and the products formed after hydrolysis were analysed by 1H NMR spectroscopy.The 5-bromine-atom is the most reactive and greater selectivity is obtained with methyllithium.
