Facile Synthesis of 4H-1,2,4-Benzothiadiazine-1,1-dioxides

Abstract

o-Bromoarylsulfonylated amidines prepared either by acylation of amidine with o-bromoarylsulfonyl chloride or through the reaction of o-bromoarylsulfoamide with lactime ether underwent Cu(I)-catalyzed intramolecular cyclization to give 4H-1,2,4-benzothiadiazine-1,1-dioxides in good yield. By varying substituents on arylsulfonyl moieties, amidines, and lactime ethers, a small library of structurally diverse 4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives was prepared.

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxidesviathree component SuFEx type reaction

“… 3 In addition, benzothiadiazines (3) are patented as ATP-sensitive potassium channel modulators for the treatment of respiratory, central nervous, and endocrine system disorders. 4 1,2,4-Thiadiazinane 1,1-dioxides of this type may be formed by various methods; 5–13 most closely related to the present work is the [2 + 2 + 2] sulfa Staudinger cycloaddition of sulfonylchlorides and imines, in which case β-sultams may also be formed through the corresponding [2 + 2] cycloaddition. 14,15 α,β-Unsaturated sulfonyl fluorides 4 are so far rarely encountered as starting materials for organic synthesis.…”

Novel Convenient Approach to 6-, 7-, and 8-Numbered Nitrogen Heterocycles Incorporating Endocyclic Sulfonamide Fragment

“…They are widely used in modern drugs design [ 1 ]. In particular, heterocyclic compounds of different size bearing an endocyclic pharmacophore sulfonamide fragment reveal a wide range of biological effects, including enzymes inhibition, antihypertensive [ 1 , 2 , 3 , 4 ], antimicrobial [ 5 ], and antiviral activity [ 6 ]. Benzothiadiazine- S , S -dioxides were used in the design of phosphodiesterase 7 inhibitors [ 7 ], HIV protease inhibitors [ 8 ], ATP-sensitive potassium channel openers exhibiting different tissue selectivity profiles [ 9 ], potent antiviral agents against HCMV, antagonists of the human CCR5 receptor [ 6 ], nonnucleoside human cytomegalovirus selective inhibitors [ 10 ], α 1 -adrenoceptor antagonists [ 11 ], drugs for treatment of cancer and the early stages of Alzheimer disease [ 12 ], human herpes virus (HHV-6) and Varicella-Zoster virus [ 10 ], and ligands for complexation TACe inhibitors [ 13 ] and others.…”

“…Many methods have been developed for the synthesis of fused six-membered cyclic sulfonamides, although each of them has some drawbacks and limitations (see e.g., [ 2 , 12 ] and references therein). The main method for the preparation of monocyclic 1,2,4-thiadiazine 1,1-dioxides is the condensation of 2-chloroethyl sulfonyl chloride with amidines [ 16 ].…”