Chlorovinyl ketones, with 4-aminothiazoles

Salts of 4-aminothiazoles react with chlorovinyl ketone (82) or with /3-diketones (83) at 140°C to yield the thiazoio[3.4-u]pyrimidine derivatives (84) (Scheme 58) (240). 

Bridgedhead thiazolo[3,2-a]pyrimidines, and their isosteres occupy a unique place in medicinal chemistry due to their wide application as drug and drug-intermediates [7-11]. Several methods are known for synthesis of thiazolo[3,2-a]pyrimidine derivatives, from 2-mercaptopyrimidines and a-halo ketones, and by cyclocondensation of a-aminothiazoles with P-diketones, P-keto aldehydes, and their acetals, P-chlorovinyl ketones and aldehydes. 

This nucleophilic reactivity of 2-aminothiazoles has been used to prepare biheterocyclic compounds. Thus 2-aminothiazole reacts with chlorovinyl methyl ketone yielding 5-methyl-thiazolo[3,2-a]pyrimidinium chloride (Scheme 109). In the presence of formaldehyde, aminothiazoles react with ends affording condensation products, through the intermediacy of Mannich bases (Scheme 110). In acidic medium and at higher temperatures, condensation of 4-aryl-2-aminothiazole with benzaldehyde takes place at the C-5 position (Scheme 111). The same orientation is observed when 2-amino-4-methylthiazole is alkylated by secondary or tertiary alcohols in 85% sulfuric acid (Scheme 112). 

---