Synthesis of Indazoles Base-catalyzed tandem carbon–carbon followed by nitrogen–nitrogen bond formations quantitatively converted N-alkyl-2-nitro-N-(2-oxo-2-aryl-ethyl)-benzenesulfonamides to 2H-indazoles 1-oxides under mild conditions. Triphenylphosphine or mesyl chloride/triethylamine-mediated deoxygenation afforded 2H-indazoles.

Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence of two heterocyclic cores connected by a spacer of variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both heterocyclic rings were assembled on resin in a combinatorial fashion.

The quality of the most commonly used support for solid phase syntheses, polystyrene resin cross linked with 1% of divinylbenzene, differs considerably even among different lots of resin from the same source. Determination of the swelling capacity of resins before carrying out solid-phase synthesis represents a very simple means of nondestructive pre-synthetic resin characterization.

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In continuation of our efforts to develop novel and efficient polymer-supported routes, leading to heterocyclic derivatives with potentially attractive pharmacological properties, we turned our attention to thiazolo [2,3,b]quinazolines. A survey of the literature revealed that a quinazoline ring fused with thiazole exhibits a wide range of biological activities, 1-3 including antifungal 4 and antibacterial activities. [4][5][6]3,b]quinazoline derivatives were also tested for their application as herbicides for the agricultural industry. 7 To date, only solution-chemistry syntheses have been described. Narang et al. 5,8 reported the first synthetic route to thiazoloquinazolines in solution by refluxing the appropriate R-haloketones with 2-carbethoxy-phenylthiourea. Subsequently, Schadev et al. 1 used 2-aminobenzonitrile and 4-chloro-2-aminobenzonitrile with R-thiocyanoketones in the presence of hydrochloric acid to synthesize thiazolo[2,3,b]-quinazolines and Sharma et al. 9 condensed isatin with allyl isothiocyanate in the presence of aqueous alcoholic potassium hydroxide. Dhami et al. 5 condensed anthranilic acid with 2-chlorothiazole. Chern et al. 10 described a multistep route from 2-thioxo-1H,3H-quinazolin-4-one leading to 3-methylthiazolo[2,3-b]quinazolin-5-one, that was further derivatized. Although some of the routes described provided respectable yield, in all reported syntheses the conditions for cyclization of acyclic precursor were severe. The harsh conditions limited the diversity of accessible derivatives. Here we report the first solid-phase synthesis of thiazolo[2,3,b]quinazoline accomplished under mild conditions and amenable to high throughput/combinatorial synthesis.Our solid-phase synthesis of thiazolo[2,3,b]quinazoline is based on the use of anthranilates and bromoketones as key building blocks and diversity elements. Anthranilates are versatile synthons providing access to diverse fused heterocyclic systems. Their application for polymer-supported syntheses of heterocycles is employed frequently and includes the synthesis of quinazolin-4-ones, 11-14 quinazoline-2,4-diones, 15-21 4-hydroxyquinolin-2-ones, 22 2-amino-benzooxazin-4-ones, 23 2-thioxoquinazoline-4-ones, 24 1,4-benzodiazepine-2,5-diones, [25][26][27][28][29] and pyrrolo[2,1-c][1,4]benzodiazepines. 30,31 We have used anthranilates for syntheses of quinazolin-4-ones 32 and recently 2-substituted-3-hydroxy-4(1H)-quinolinone-7-carboxamides. 33 Our first effort to prepare thiazolo[2,3,b]quinazolines was based on a solid-supported synthesis of 2-thioxoquinazoline-4-ones using anthranilates as the key synthon. This was followed by alkylation with bromoketones and subsequent formation of the six-membered quinazolinone ring. Combination of these two types of building blocks allows for the preparation of thiazolo[2,3,b]quinazolines with two diversity positions: one on the carboxylic benzene ring and the second on position 3 of the thiazolo ring.Briefly, Rink amide resin 1, after cleavage of the Fmoc group, was acylated with commercially avail...

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A resin capsule is a permeable container for resin beads designed for multiple/combinatorial solid-phase organic synthesis. Resin capsules consist of a high density polyethylene ring sealed with peek mesh on both sides. The cylindrical shape of resin capsules enabled space-saving packing into plastic column-like reaction vessels commonly used for solid-phase organic synthesis. Resin capsules have been evaluated for their use in combinatorial synthesis, and a set of model compounds with excellent purity was prepared.