Guanidines heterocyclic compound synthesi

An efficient, practical solid-phase synthesis of a variety of bis-hetero-cyclic compounds was developed starting from resin-bound orthogonally protected lysine (Fig. 10). Tetraamines 36 were synthesized by exhaustive reduction of resin-bound tetraamides 35. Cyclization with different commercially available bifunctional reagents such as cyanogen bromide, thio-carbonyldiimidazole, carbonyldiimidazole, and oxalyldiimidazole yielded the corresponding bis-heterocyclic compounds bis-cyclic guanidines 37,39 bis-cyclic thioureas 38, bis-cyclic ureas 39, and bis-diketopiperazines 40, respectively.40 Reduction of compounds 40 led to bis-piperazines 41. 

Many biologically active compounds contain cyclic ureas, including inhibitors of human immunodeficiency virus (HIV) protease and HIV replication [70]. Kim et al. [71] presented an illustration of the synthesis of oligomeric cyclic ureas as nonnatural biopolymers. Applying the libraries from libraries [72] concept, triamines [65] such as those described earlier were used as templates for the generation of different heterocyclic compounds such as cyclic ureas, cyclic thioureas, and bicyclic guanidines [65]. The cyclizations to obtain the five-membered ring cyclic ureas and cyclic thioureas were... 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

Nucleophilic cyclization reactions are widely used for the synthesis fluoroalkyl heterocycles. This process relies on the use of fluorinated building block for the introduction of perfluoroalkyl group into heterocycle. For example, heating of compound 30 with urea or guanidine results in the formation of the corresponding pyrimidines 31 and 32 in moderate yield (Fig. 7.10). 

More than a third part of all the described principal syntheses of pyrimidines bearing fluorinated alkyl at C-4 atom commences from fluorinated p-dicarbonyl compounds 699. The chemistry of these bis-electrophiles was reviewed recently [411, 412] therefore, their preparation is not discussed herein. This synthesis of pyrimidines is fairly general (Table 34) it allows for introducing aliphatic, alicyclic and aromatic p-diketones (Entries 1-10), p-ketoesters (Entries 11-16), and cyclic P-ketoamides (Entry 17). Presence of some functional groups, such as additional ester moiety (Entry 15), is more or less tolerated, whereas increasing steric hindrance results in lowered yields of the products (Entry 10). A scope of conunon NCN binucleophiles include amidines (Entries 1, 11, 12, 17), (thio)urea and its derivatives (Entries 2-4), guanidines (Entries 5,16) and biguanides (Entry 6). Electron-rich amino heterocycles e.g. aminoazoles and even 2,6-diaminopyridine) are excellent NCN binucleophiles for the principal synthesis of fused pyrimidine derivatives (Entries 7-10, 13-15). 

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