Patent ID: 6713615
Filing Date: 2004-03-30
Classification: C07H

Abstract:
A process for preparing Compound (V) defined below, which comprises the steps of:(A) providing Compound (I) of the formula: wherein R1 and R2, which may be the same or different, are a hydrogen atom, formula â€”COâ€”RA wherein RA is a C1-3 alkyl group, C1-3 alkyl group substituted with 1-3 halogen atoms, C1-3 alkoxy group, phenyl group, phenyloxy group, benzyloxy group, or phenyl group substituted with 1-3 substituents selected from the group consisting of C1-3 alkyl group, C1-3 alkoxy group, nitro group, cyano group, halogen atom, acetyl group, phenyl group and hydroxy group, or a silyl group substituted with 2-3 substituents selected from the group consisting of C1-4 alkyl group, phenyl group and benzyl group, by reaction of erythromycin with ethylene carbonate, subsequent reduction of ketone in 9-position, and optional protection of hydroxy groups in 2â€²- and/or 4â€ -positions, (B) reacting Compound (I) with a compound of the formula: wherein A is CH&boxH;CH or Câ‰¡C; R5 and R6, which may be the same or different, are a C1-7 alkyl group, and optionally protecting a resulting 3-hydroxy group, to obtain Compound (II) of the formula: wherein R3 is the same as R1 defined above; R2 and A are as defined above, (C) reacting Compound (II) with a compound of the formula: Xâ€”R4â€ƒâ€ƒ(2) wherein X is a halogen atom; R4 is the formula: wherein R7 and R8 are a hydrogen atom or, alternatively, they form a benzene nucleus together with the adjacent carbon atoms, or the formula: wherein Ar is a pyridyl group, quinolyl group or aryl group, to obtain Compound (III) of the formula: wherein A, R2, R3 and R4 are as defined above, (D) reacting Compound (III) with a compound of the formula: wherein R9 is a hydrogen atom, chlorine atom, linear or branched C1-4 alkyl group, C1-3 alkoxy group, phenyl or benzyl group; R10 and R11, which may be the same or different, are a chlorine atom, linear or branched C1-4 alkyl group, C1-3 alkoxy group, phenl group or benzyl group, to obtain Compound (IV) of the formula: wherein A, R2, R3 and R4 are as defined above, and (E) subjecting Compound (IV) to carbonylation at 9-position, carboxylation at 3-position, 11,12-cyclic carbamation and deprotection of 2â€²-hydroxy group, to obtain Compound (V) of the formula: wherein A and R4 are as defined above.