1473-47-8

Upstream product

• 163222-89-7 1,2-dihydrocyclobutabenzene-1-carboxylic acid 
• 6809-91-2 1-cyanobenzocyclobutane 
• 7315-17-5 3-(2-chloro-phenyl)-propionitrile 

Downstream Products

• 1459789-79-7 N-(2-bromophenyl)-N-methyl-1,2-dihydrocyclobutabenzene-1-carboxamide 

Relevant academic research and scientific papers

Synthesis of 3,3-disubstituted oxindoles by palladium-catalyzed asymmetric intramolecular α-arylation of amides: Reaction development and mechanistic studies

Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency. Copyright

Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8- (trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury

Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the α position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.

TRICYCLIC LACTAM DERIVATIVES AS 11-BETA HYDROXYSTEROID DEHYDROGENASE INHIBITORS

Compounds of formulae (I) and (I bis) are useful as 11BETA-HSD1 inhibitors for treatment of obesity.

Torquoselectivity in the electrocyclic conversion of benzocyclobutenes to o-xylylenes

The conrotatory electrocyclic opening of benzocyclobutene to o-xylylene was studied by means of ab initio molecular orbital calculations. The theory developed earlier to predict the torquoselectivity of ring opening of 3-substituted cyclobutenes was found to be applicable. Experimentally, the ring opening of several 7-substituted benzocyclobutenes, such as the cyano, methoxycarbonyl, and formyl derivatives was examined. o-Xylylenes were obtained in which cyano or ester groups had rotated outwards, whereas the formyl group turned inwards. N,N-Dimethylbenzocyclobutene-7-carboxamide exhibited 75% inward torquoselectivity upon ring opening. A reversal of mode was seen with the 7-methyl derivatives of benzocyclobutene-7-carbonitrile and methyl benzocyclobutene-7-carboxylate in that the 7-methyl substituent manifested overwhelming outward motion.