4-Substituted-aminothieno

Starting from 2-amino-3-cyano-4,5-dihydrothiophenes 60 the derived 2-benzamido derivatives 61 were treated with cyclohexylamine, morpholine, piperidine, or pyrrolidine to yield the respective 5,6-dihydro-2-phenyl 4-substituted aminothieno[2,3-d]pyrimidines 62a-d (83CPB401). In the presence of tin(IV) chloride, benzamides 61 reacted with acetic (or propionic) anhydride to give the corresponding 3-acetyl(or propionyl)thieno[2,3-[Pg.206]

Substituted aminothieno[3,2-d]pyrimidines 247 were obtained from o-aminocarbonitriles 246 by a four-step reaction sequence as described for the corresponding thieno[3,2-<7]pyrimidine isomer 59 (91EUP452002). 

Numerous syntheses involving formation of the thiophene ring have been reported. Nucleophilic substitution by ethyl mercaptoacetate of 2-chloro-3-cyanopyridine with subsequent base-promoted cyclization yields ethyl 3-aminothieno[2,3-i]pyridine-2-carboxylic acid, which is easily transformed by standard methods into the parent compound (258 Scheme 63) (74JHC975, 76JHC273). 

Approach G involves the successive formation of the N(3)-C(4) and C(2)-N(3) bonds of the pyrimidine ring during cascade heterocyclization. Such transformations can be exemplified by condensation of substituted 2-alkoxycarbonyl-3-(R2-car-bonyl)aminothieno[2,3-6]pyridines 95 with primary amines or hydrazine giving rise to fused pyrimidin-4(3A)-ones 96 (1993PH26, 1997KGS847). In the case of R4 = EtO, the reaction gives pyrimidine-2,4-dione derivatives 97 as the final products (1993PH95). 

Few examples of substitution reactions on intact heterocycles have been reported. Notable is the synthesis of 3-aminothieno[3,4-d]isothiazole 1,1-dioxides (51) by the fusion of thieno[3,4-d]iso-... 

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