Synthesis of Quinazolines from N-(2-Nitrophenylsulfonyl)iminodiacetate and α-(2-Nitrophenylsulfonyl)amino Ketones via 2H-Indazole 1-Oxides

Abstract

Base-catalyzed rearrangement of 2H-indazoles 1-oxides, prepared by tandem carbon-carbon followed by nitrogen-nitrogen bond formations from easily accessible N-alkyl-2-nitro-N-(2-oxo-2-aryl-ethyl)-benzenesulfonamides using glycine, 2-nitrobenzenesulfonyl chlorides and bromo ketones/acetates, yielded high purity quinazolines.

Traceless Solid-Phase Synthesis of 1′H-Spiro[Pyrrolidine-3,2′-quinazolin]-2-ones and 1′H-Spiro[Piperidine-3,2′-quinazolin]-2-ones via Lactamization of 1,2-Dihydroquinazoline-2-carboxylates

“…Resin 3 , ∼250 mg, prepared according to the published procedure, was washed 3 × DCM and 3 × DMF. A solution of 0.1–0.5 M DBU (1 mmol, 38 μL for the 0.1 M solution −5 mmol, 188 μL for the 0.5 M solution) in 2.5 mL of DMF was added, and the resin slurry was shaken at room temperature or 50 °C (see Supporting Information) overnight.…”

“…The growing side chain of the amino acids caused deceleration of the ring expansion reaction rate. Compared with analogous reported glycine derivatives (0.1–0.2 M DBU, 10 min to 16 h) with bulkier side chains, the substrates evaluated in this work necessitated an increase in the concentration of DBU, an extension in the reaction time to the order of days and the use of elevated temperature (details in Supporting Information). Electron-withdrawing substituent CF 3 (R substituent) moderated the reaction conditions to 0.1 M DBU in 2 days.…”

“…The presence of a chiral carbon prompted us to carry out chiral separation of two compounds prepared using l - and d -ornithine (see Supporting Information for details). The separation revealed full epimerization, a result that supports the suggested mechanism of ring expansion …”

Solid phase synthesis of functionalized indazoles using triazenes – scope and limitations

“…18 While the solid phase organic synthesis (SPOS) of small-sized molecules has emerged as an important tool for the generation of heteroaromatic scaffolds in drug discovery, 19 there are only a few reported examples for the synthesis of indazoles in solid phases. [20][21][22] Therefore, in order to benet from the possibility of rapid syntheses without tedious and time-consuming purication steps, we intended to develop a straightforward method to gain diverse indazoles via solid phase chemistry. While according to the rst synthesis of indazoles on solid supports, 20 the indazole unit was formed by a Lewis acid-catalyzed cyclization and the cleavage of the indazole from the solid phase in a second step, we decided to follow a route that would allow the formation of the indazole and cleavage off the resin in only one step.…”

Solid‐Phase Synthesis of 3,4‐Dihydroquinoxalin‐2(1H)‐ones via the Cyclative Cleavage of N‐Arylated Carboxamides

“…[2] Resin-bound N,N-disubstituted Nos amides are an intriguing class of acyclic intermediates that can be converted to diverse nitrogen heterocycles.T he critical feature of these advanced intermediates is an acidic proton on the alphac arbon of the N-alkyl group due to the presence of an electron-withdrawing substituent, R 2 (Scheme 1). Exposure to ab ase, typically DBU,t riggers C-arylation [6,19,20] via at ype of Smiles rearrangement [21] involving the spiro-Meisenheimer intermediate 2.T hese C-aryl derivatives 3 have been usedt op repare various nitrogen heterocycles,i ncluding indazoles and their N-oxides, [19,22] quinazolines, [23] indoles [24] andindolin-2-ones. [25] Interestingly, N,N-disubstituted-2-nitrobenzenesulfonamides prepared from the polymer-supported aamino acid secondary amides 4 undergo another type of Smiles rearrangement, leading to N-aryl derivatives 7.…”