Thiazolo 3,2-a pyrimidine-6-carboxylates

Thiazolo[3,2-a]pyrimidine-6-carboxylate (363) was prepared in 15% yield in the reaction of dimethyl 2-thiazolyldithiocarbonimidate and diethyl malonate at 140°C for 24 hr (88CP1232904). 

The reaction of 2-aminothiazole and isopropylidene bis(methylthio)-methylenemalonate (459, R2 = R3 = SMe) or 1-methylthioalkylidenema-lonates (459, R2 = Me, Et, Ph R3 = SMe) in boiling ethanol for 2.5 hr or in dimethylformamide at 120-130°C for 4-5 hr, gave 2-substituted 5-oxo-5//-thiazolo[3,2-a]pyrimidine-6-carboxylates (462) in good yields (89S-317). Similarly, in boiling ethanol, 2-substituted 4-oxo-4//-pyrido[l,2-a]-pyrimidine-3-carboxylic acids (463) were obtained in 80-85% yields. When anilines were reacted with isopropylidene bis(methylthio)methy-lenemalonate (459, R2 = R3 = MeS), (methylthio)(arylamino)methylene-malonates (464) were obtained 61-88% yields. 

Liu et al., reported the synthesis of ethyl 5-(2,6-dichlorophenyl)-7-methyl-2-(1 -naphthylmethylene)-3 -oxo-2,3 -dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate 37 (Scheme 15). The reaction of ethyl 2-mercapto-4-methyl-6-(2,6-dichlorophenyl)-l,6-dihydro-pyrimidine-5-carboxylate, ethyl chloroacetate and naphaldehyde in acetic acid and acetic anhydride afforded the target molecule 37. In the molecular, the thiazolo[3,2-a]pyrimidine and naphthalene systems are essentially coplanar, with a dihedral angle between the combined plane and the mean plane of the benzene ring of the 2,6-dichlorophenyl substituent of 94.7(4)° [39]. 

Condensation of 3-(2-amino-4-thiazolyl)comnarin 91 with a-acetyl-y-butyrolactone in a mixture of polyphosphoric acid and POCI3 afforded thiazolo[3,2-a]pyrimidin-5-one 92, while condensation of 91 with P-keto esters gave 7-methyl-3 -(2-oxo-2H-chromen-3 -yl)-5 H-[ 1,3]thiazolo [3,2 -a]pyrimidin-5 -ones 93(Scheme 42). Reaction between 91 and diethyl 2-(methoxymethylene)malonate imder solvent-free conditions yielded 3-(2-oxo-2H-chromen-3-yl)-5-oxo-5H[l,3]thiazolo[3,2-a]pyrimidine-6-carboxylate 94 [67],... 

The 5-oxo-5//-oxazolo[3,2-a]pyrimidine-6-carboxylate (193) reacts faster than the corresponding thiazolo analogue with hydrazine, which is explicable on the basis of the greater electronegativity of oxygen. The initial attack is at C-2 or more likely at C-8a the ring-opened product is subsequently cyclized to a triazine (71JCS(C)1615). 

---