2,1-Benzothiazine 2,2-Dioxides. 8*. Synthesis and Structure of 2'-Amino-2-Oxo-1,2-Dihydro-6'H-Spiro-[Indole-3,4'-Pyrano[3,2-c][2,1]Benzothiazine]-3'-Carbonitrile 5',5'-Dioxides

New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylates

“…By the example of allyl [ 31 ], isopropyl ( Figure 3 ) and benzyl ( Figure 4 ) derivatives it has been conclusively proven that actually methyl 4-methyl-2,2-dioxo-1 H -2λ 6 ,1-benzothiazine-3-carboxylate ( 3 ) is alkylated exclusively at the nitrogen atom independently from the structure of alkyl halide. Simultaneously, it has been found that the tendency to form solvates with various organic solvents previously mentioned for 4-hydroxy-2,2-dioxo-1 H -2λ 6 ,1-benzothiazines over and over again [ 17 , 32 ] is also typical for their 4-methyl-substituted analogs. In particular, the ability of methyl 1-benzyl-4-methyl-2,2-dioxo-1 H -2λ 6 ,1-benzothiazine-3-carboxylate ( 5g ) to form a monosolvate easily from methanol already in crystallization has been found ( Figure 4 ).…”

Updating the CSIC Reaction (2003–2020)

“…[35] Entry NH-CSICr precursor The synthesis of diversely substituted 1H-benzo[c][1,2] thiazin-4(3H)-one 2,2-dioxides III (Figure 2) follows a well and simple three-step protocol proposed by Lombardino in the seventies, [44] consisting of the CSICr of a N-alkyl-N-(methylsulfonyl)anthranilate, obtained from the reaction of an anthranilate and methanesulfonyl chloride, followed by Nalkylation of the resulting intermediate. This procedure has been used later by other authors without significant modifications, under conventional conditions [43,[45][46][47][48][49][50][51][52][53][54][55][56] or solid-phase, a very appropriate method for the combinatorial synthesis of heterocyclic compound libraries, albeit in low chemical yields. [57] Scheme 15.…”

“…[47,48] Based on in a house high-throughput screening, followed by the appropriate biological evaluation, 1,5-dihydropyrazolo [4,3-c][2,1]benzothiazines 140 and 141 ( Figure 3) were identified as novel allosteric focal adhesion kinase (FAK) inhibitors showing powerful kinase selectivity. [48] Ukrainets a,b,d, malononitrile, and N-substituted isatins (142 a,b) and to give 1'-(H, allyl)-2-amino-6-(methyl, allyl, H)-2'-oxo-6H-spiro [benzo[c]pyrano[2,3-e][1,2]thiazine-4,3'-indoline]-3-carbonitrile 5,5-dioxides 143 a-e in good yields [51] (Scheme 33), whose structure has been unequivocally assigned as shown by detailed NMR analysis, and confirmation by X-ray diffraction analysis of one of the final compounds. [51] The same year Shemchuk and colleagues have reported related chemistry leading to similar spiro compounds of type 144 in good chemical yields (64-83 %) (Scheme 34) by threecomponent catalyzed reaction of 1-ethyl-1H-benzo[c][1,2] thiazin-4(3H)-one 2,2-dioxide (95 c) with appropriate and conveniently substituted isatins 142 c-g and malononitrile, in the presence of triethanolamine under reflux for 30 min in ethanol (Scheme 34).…”

“…[48] Ukrainets a,b,d, malononitrile, and N-substituted isatins (142 a,b) and to give 1'-(H, allyl)-2-amino-6-(methyl, allyl, H)-2'-oxo-6H-spiro [benzo[c]pyrano[2,3-e][1,2]thiazine-4,3'-indoline]-3-carbonitrile 5,5-dioxides 143 a-e in good yields [51] (Scheme 33), whose structure has been unequivocally assigned as shown by detailed NMR analysis, and confirmation by X-ray diffraction analysis of one of the final compounds. [51] The same year Shemchuk and colleagues have reported related chemistry leading to similar spiro compounds of type 144 in good chemical yields (64-83 %) (Scheme 34) by threecomponent catalyzed reaction of 1-ethyl-1H-benzo[c][1,2] thiazin-4(3H)-one 2,2-dioxide (95 c) with appropriate and conveniently substituted isatins 142 c-g and malononitrile, in the presence of triethanolamine under reflux for 30 min in ethanol (Scheme 34). [52] The same protocol, but using ethyl cyanoacetate, afforded analogous spiro compounds of type 145 in good yields also ranging from 46 to 63 % (Scheme 34).…”

Synthesis, Modification, and Anticonvulsant Activity of 3′‐R1‐Spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones Derivatives

“…The presence of several reaction centers in molecule of isatin allows its utilization in various reactions including electrophilic substitution, alkylation, condensation, dimerization, and dipolar addition. Their significant chemical potential is reasonable within “hybrid–pharmacophore” approach to the development of novel bioactive compounds; also, they may be considered as valuable reagents for the formation of different carbo‐cyclic and hetero‐cyclic systems . Recently, a lot of scientific groups are interested in the possibility of spiroindolinetetrahydroquinazoline synthesis that may be conducted via cyclo‐condensation of isatins with various 1,3‐diamines and their analogues (amides and N ‐benzyl‐(aryl)amides of 2‐aminobezoic acid) .…”