PURPOSE: To obtain a new thiourea derivative useful as a production intermediate for N-biphenylmethylthiazoline derivative which is useful as an agent for the treatment of circulatory diseases.
CONSTITUTION: This thiourea derivative is a compound of formula 1 [R1 is (substituted) lower cycloalkyl, a (substituted) phenyl or a lower alkenyl; R2 is a halogen or cyanophenyl), e.g. N-benzoyl-N'-(2'-cyanobiphenyl-4-yl) methylthiourea. The compound can be produced by reacting an isothiocyanate derivative of formula 2 with a benzylamine compound of formula 3 in an aprotic polar solvent at 0°C to room temperature. An N-biphenylmethylthiazoline of formula 4 [R3 is H or an alkyl; Y is a (protected) carboxyl or a (protected) carboxymethyl; Z is CN or a (protected) tetrazolyl] can be produced from the thiourea derivative. For example, a compound of formula 4 wherein Z is CN can be produced by reacting a compound of formula 1 wherein R2 is cyanophenyl with a compound of formula 5 (X1 is a halogen; Y1 is a protected carboxyl or a protected carboxymethyl) and optionally eliminating the carboxyl- protecting group.
SAKAE SHINYA
HIRATA AKIKAGE
