Efficient one‐pot synthesis of s‐triazolo[3,4‐b]‐[1,3,5]thiadiazines containing a chiral side chain by double mannich type reaction

Abstract

An efficient and convenience method has been developed via a one‐pot double Mannich type reaction for the synthesis of the important chiral s‐triazole derivatives: (S)‐3‐α‐phenylethyl‐2,4‐dihydro‐5‐aryl‐oxymethyl‐1,2,4‐triazolo [3,4‐b] ‐1,3,5 ‐thiadiazines.

The Mannich reaction in the synthesis of N,S-containing heterocycles. 7. Effective one-pot synthesis of derivatives of spiro[3,5,7,11-tetraazatricyclo-[7.3.1.02,7]tridec-2-ene-13,4′-piperidine]

“…It follows from multitudinous data in the literature that aminomethylation of 2-mercaptoazoles and -azines is a general method for the preparation of condensed derivatives of 1,3,5-thiadazines. In particular, derivatives of sym-triazolo [3,4-b][1, 3,5]thiadiazine [9][10][11][12][13][14][15][16], thiazolo [3',4':1,5][1,2,4]triazolo [3,4-b][1, 3,5]thiadiazine [17], imidazo[2,1-b][1, 3,5]thiadiazine [18,19], 1,2,4-triazino [3,2- 3,5]thiadiazine [19], and 1,3,5-thiadiazino[3,2-a]benzimidazole [20] have been obtained by "double" Mannich condensations. We have shown previously with a series of 2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates that, depending on the structure of the substrate, aminomethylation can lead to the formation of _______ * For 3,5]thiadiazine [21,22], 3,7-diazabicyclo[3.3.1]nonane [23], or tricyclic products [24].…”

Synthetic Methods and Pharmacological Potentials of Triazolothiadiazines: A Review

“…On the other hand, the prior mention [ 67 , 68 ]. The Mannich reaction involves the interaction of 1,2,4-triazole-5-thiones 94 with formaldehyde and different primary amines in ethanol.…”

Design and Synthesis of Pyrido[2,1-b][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction

“…One of the most effective approaches to 1,3,5-thiadiazines is based on the double Mannich-type reaction of thioamides, dithiocarbamates or related S , N -binucleophilic species with primary amines and formaldehyde. − Cyclic thioamides (γ- and δ-thiolactams, 2-mercaptoazoles, -azines, or their 2-thioxotautomers) can also be successfully employed in this reaction, giving rise to a variety of ring-condensed 1,3,5-thiadiazines. In fact, the related syntheses of 1,2,4-triazolo[3,4- b ][1,3,5]thiadiazines, − imidazo[2,1- b ][1,3,5]thiadiazines, , 1,2,4-triazino[3,2- b ][1,3,5]thiadiazines, thiazolo[3′,4′:1,5][1,2,4]triazolo[3,4- b ][1,3,5]thiadiazines, 1,3,5-thiadiazino[3,2- a ]benzimidazoles, cyclopenta[ g ]pyrido[2,1- b ][1,3,5]thiadiazines, bis (pyrido[2,1- b ][1,3,5]thiadiazin-7-yl)methanes, pyrimido[2,1- b ][1,3,5]thiadiazines, and pyrimido[4,3- b ][1,3,5]thiadiazines − have been reported (Scheme ).…”

“…This effective and time-saving protocol is based on the use of inexpensive, readily available building blocks. In contrast to related double Mannich reactions, − no catalyst is required for this process. In most cases, the obtained pyrido[2,1- b ][1,3,5]thiadiazines 8 were pure enough for analytical purposes that allowed us to exclude any purification steps.…”