Thiazolylimidazole derivatives an their use as inhibitors of microsomal triglyceride transfer protein

A process for the preparation of a compound of formula (I):

• in which:
• G represents a bond or a divalent radical chosen from the groups g1, g2 and g3 below:
• R1 is chosen from hydrogen and an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylcarbonyl or alkoxycarbonyl radical;
• R2 and R3, which may be identical or different, are chosen, independently of each other, from a hydrogen atom, an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl radical and a radical —NRR′;
• R4, R5 and R6, which may be identical or different, are chosen, independently of each other, from a hydrogen atom and an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl radical;
• R and R′, which may be identical or different, represent, independently of each other, a hydrogen atom or a radical chosen from alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• or together form, with the nitrogen atom that bears them, a heterocycle, or together form the double bond of an alken-1-yl radical;
• Y represents an oxygen or sulfur atom;
• and
• Z represents —NH— or an oxygen atom;
• comprising reacting a compound of the formula (II):
• in which T represents a labile protecting group, with ethyl R3-bromopyruvate, in a polar solvent, in the presence of an excess of base, at a suitable temperature, for a period ranging from 1 to 40 hours,
• so as to form a thiazolyl ring and produce a compound of formula (III):
• saponifying the compound of the formula (III) with an alkali metal or alkaline-earth metal hydroxide base, in polar medium, at room temperature, for a period of 1 to 12 hours, so as to form a salt of formula (IV):
• in which M+ represents the alkali metal or alkaline-earth metal cation derived from the base that is used for the saponification reaction,
• hydrolyzing the compound of formula (IV) to a compound of formula (V):
• converting the compound of formula (V) to a corresponding amide of formula (VI):
• via the action of an amine of formula (VIa):
• in the presence of a base, and a catalyst, in a polar aprotic solvent, at room temperature, for 1 to 50 hours,
• deprotecting of the amine function of the piperidine ring of VI, via the action of an organic or mineral acid, in dichloromethane or dioxane medium, at room temperature, for a few minutes to several hours, to give a compound of formula (VII):
• subjecting said compound VII to the action of:
• in which X represents a halogen atom,
• in the presence of a base, and a catalyst, in a polar aprotic solvent, at room temperature, for 1 to 50 hours,
• to give a compound of the formula (VIII):
• and subjecting VIII to a cyclization reaction to form an imidazole ring, in the presence of a cyclizing agent, acting as a solvent, at a suitable temperature,
• to give a compound of the formula (I).