Thiazolo 5,4-c pyridines

A useful method for the preparation of functionalised thiazoles has been described. Palladium catalysed cross coupling reactions between 4-thiazolyl-5-acetyl triflates 36 and alkynes afforded 4-alkynyl-5-acetylthiazoles 37 in good yields (56-82%). If 37 is then treated with ammonia in methanol, thiazolo[5,4-c]pyridines 39 are formed, probably via the intermediate imine 38 which then undergos a regioselective 6-endo dig cyclisation <99EJOC3117>. 

Convenient syntheses of the rare thiazolo[5,4-c]pyridine 279 and 4-aminopyridine-3-thiol (281) systems have been achieved (Scheme 83) [88CI(L)302]. Thus, metalation of 263 followed by quenching with di-isopropylthiocarbonyl disulfide affords, in high yield, compound 278. Base-induced cyclization affords the thiazolopyridine 279, while treatment... 

A similar strategy has been successfully used to synthesize 2-substituted thiazolo[5,4-c]pyridines (90JHC563). 

Arylthiazole 33 with a cyanoacetate moiety at C-4 is prepared via a novel cyclization from iminothiazine hydroperchlorate 31, readily available from the reaction of ethyl 2-cyano-3,3-bis(methylthio)acrylate and phenylthioamide <04H(63)2319>. Treatment of 31 with phenacyl bromide and triethylamine in methanol generates 33, which is converted to the thiazolo[5,4-c]pyridine 34 under acidic conditions. 

To a three-necked flask equipped with gas inlet and outlet were added a stir bar, 6.0 g sulfur, and 40.0 g l-methyl-4-piperidone. The flask was cooled with ice, and under stirring ammonia gas was bubbled into the mixture. The temperature of the reaction was maintained between 40 and 50°C. The introduction of ammonia was continued until the last traces of sulfur disappeared (usually 2 h). The excess ammonia was removed by connecting the gas outlet to vacuum while stirring. The warm, viscous liquid was diluted with 200 mL 50% potassium carbonate solution, and the mixture was extracted with five 100-mL portions of ether. The ether solution was dried over potassium carbonate, filtered, and treated with hydrogen chloride. A yellow precipitate of l,6 -dimethyl-2, 4 5 6 7 7a -hexahydrospiro[piperidine-4,2 -thiazolo[5,4-c]-pyridine]dihydrochloride formed immediately, which was filtered, washed with ether, and dried under reduced pressue over CaCb to afford 53.5 g of product, m.p. 200-205°C. An analytical sample was prepared by... 

Isothiocyanatopyridine, 1-70107 Thiazolo[4,5-ft]pyridine, T-70166 Thiazolo[5,4-ft]pyridine, T-70168 Thiazolo[4,5-c]pyridine, T-70167 Thiazolo[5,4-c]pyridine, T-70169 Thieno[3,2-eflpyrimidine, T-60205... 

A soln. of 13.8 g. 2-phenyl-4-( -aminoethyl)thiazole, formic acid, and 30%-formaldehyde refluxed overnight 13 g. 2-phenyl-5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine.—When the phenyl group is absent, ring closure does not occur but instead the free amino group is dimethylated. F. e. s. G. Palazzo and M. Tavella, G. 92, 1084 (1962). 

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