Patent ID: 6541646
Filing Date: 2003-04-01
Classification: A61P,C07C,C07D

Abstract:
A method of preparing compounds of general formula I: in whichR1 is chosen from the group consisting of (a) OR5 where R5 represents a group chosen from amongst the group consisting of (1) a C1-C6 branched linear and ring alkyl group; (2) amongst the group consisting of a mono-, di- and tri- substituted phenyl and naphthyl group in which the substituents are chosen from amongst: hydrogen; halogen; (C1-C3)alkoxy; CN; (C1-C3)fluoroalkyl; (C1-C3)alkyl; COOH; and (b) amongst a group consisting of mono-, di and tri- substituted phenyl in which the substituents are chosen from amongst: hydrogen; halogen; (C1-C3)alkoxy; CN; (C1-C3)fluoroalkyl; (C1-C3)alkyl; COOH; R2 represents a (C1-C6) alkyl group; R3 and R4 represent independently of one another a constituent chosen from the group consisting of a hydrogen atom and a CHR6R7 group in which R6 and R7 are independently of each other chosen from amongst: hydrogen; (C1-C10)alkyl; (C1-C10)alkoxy; OH; CN; CH2CN; OCOR8; (C1-C6)fluoroalkyl; halogen; CON(R8)2; a phenyl chosen from the group consisting of mono-, di- and tri-substituted phenyl; a heteroaryl chosen from the group consisting of mono-, di and tri-substituted heteroaryl; the substituents being chosen from amongst the group consisting of: hydrogen; halogen; (C1-C6)alkyl; (C1-C10)alkoxy; CN; CF3; N3; C(R9) (R10)â€”OH; C(R9) (R10)â€”Oâ€”(C1-C4)alkyl; (C1-C6)fluoroalkyl; wherein R8 is chosen from amongst the group consisting of: hydrogen; (C1-C6)alkyl; a phenyl chosen from the group consisting of mono-, di and tri-substituted phenyl, the substituents being chosen from amongst the group consisting of hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, CN and CF3; and a benzyl chosen from the group consisting of mono-, di and tri-substituted benzyl, the substituents being chosen from amongst the group consisting of hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, CN and CF3; including the group(s) consisting of: two R8 groups form together with the nitrogen atom to which they are attached a ring with 5 to 7 atoms, and possibly comprising a heteroatom chosen from amongst the group consisting of O, S and NR9; wherein R9 and R10 are independently of one another chosen from amongst the group consisting of: (i) hydrogen and (C1-C10)alkyl; and (ii) where R9 and R10 form, together with the atom to which they are attached, a ring with 3 to 7 carbon atoms and where applicable a nitrogen atom; wherein the method comprises the following steps: a) reaction of a compound of general formula II: in which R2, R3 and R4 are as defined above and R12 represents a C1-C6 alkyl group,with an acid of general formula III: in which R1 is as defined previously, in an anhydrous medium, in order to form a compound of formula IV: R1, R2, R3 and R4 being as defined above;b) reaction of the compound of formula IV with a strong base in an aprotic solvent in order to obtain an intermediate ring compound of formula V: which, after elimination of a water molecule, forms a compound of general formula I; andc) isolation of the compound of general formula I thus obtained.