Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

Abstract

SummaryReaction of o-azidobenzenesulfonamides with ethyl carbonochloridate afforded the corresponding amide derivatives, which gave 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides through an intramolecular aza-Wittig reaction. The reaction was found to be general through the synthesis of a number of benzothiadiazine 1,1-dioxides. Acid-catalyzed hydrolysis of 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides furnished the 2-substituted benzothiadiazine-3-one 1,1-dioxides in good yields and high purity, which is the core moiety of RSV inhibitors.

Synthesis, crystal structure and docking studies of tetracyclic 10-iodo-1,2-dihydroisoquinolino[2,1-b][1,2,4]benzothiadiazine 12,12-dioxide and its precursors

“…Benzothiadiazines are an important group of heterocycles. They have been noted to have a broad spectrum of applications, including pharmacological properties as antihypertensives (Tait et al, 2005), antimicrobials (El-Maghraby et al, 1984) and antibacterials (Kamal et al, 2007), as well as in the treatment of HIV (Majumdar & Ganai, 2013), tuberculosis (Kamal et al, 2010) and cancer (Gong et al, 2018). Their roles as electrophilic asymmetric fluorination agents (Liu et al, 2000) are also significant.…”

A Route to Triazole-Fused Sultams via Metal-Free Base-Mediated Cyclization of Sulfonamide-Tethered 5-Iodotriazoles

“…The precipitate formed was filtered off and dried in a vacuum desiccator over P 2 O 5 . Although the compound was described earlier as 2-azidobenzenesulfonic acid, 39 the neutral pH of the aqueous solution is consistent with a sodium salt structure. Yield 12.881 g (88%).…”

“…Yield 895 mg (88%). Pale yellow powder; mp 150–152 °C (lit . 136–138 °C); 1 H NMR (600 MHz, CDCl 3 ): δ 8.00 (dd, J = 7.8, 1.3 Hz, 1H), 7.62 (td, J = 7.8, 1.3 Hz, 1H), 7.32–7.27 (m, 2H), 4.99 (br q, J = 5.4 Hz, 1H), 2.62 (d, J = 5.4 Hz, 3H).…”

Iodine-mediated synthesis of 3-acylbenzothiadiazine 1,1-dioxides

“…Benzothiadiazine 1,1-dioxide moieties have attracted remarkable attention in the pharmacological area because of their broad spectrum of activities [1–4], such as antihypertensive [5–6] or antiviral [7–8] and they are also used as cardiovascular agents [9–11] (Scheme 1). In this context, several synthetic methods have been developed to synthesize benzothiadiazine 1,1-dioxides and their analogues.…”