Patent ID: 6600035
Filing Date: 2003-07-29
Classification: A61P,C07D

Abstract:
A process for the preparation of a compound of Formula (I): in which:R1 is hydrogen, (C1-10)alkyl or (C1-10)alkylthio, or substituted (C1-10)alkyl or substituted (C1-10)alkylthio, wherein the substituent is selected from hydroxy, (C1-6)alkoxy, (C1-6)alkanoyloxy, halogen, mercapto, (C1-6)alkylthio, amino, (mono or di)-(C1-6)alkylamino, (C1-6)alkanoylamino, carboxy, or (C1-6)alkoxycarbonyl; R2 is a fused bicyclic ring having the formula: â€ƒwherein R4 and R5 are independently selected from the group consisting of hydrogen, (C1-6)alkanoyl, (C1-6)alkanoyloxy, amino, (C1-6)alkanoylamino, (mono or di)-(C1-6)alkylamino, hydroxy, (C1-6)alkoxy, sulpho, mercapto, (C1-6)alkylthio, (C1-6)alkylsulphinyl, (C1-6)alkylsulphonyl, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, halogen, carboxy, carboxy salts, pharmaceutically acceptable in-vivo hydrolysable carboxy esters, arylcarbonyl, and unsubstituted or substituted (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, and aryl(C1-6)alkyl groups; m is 2 or 3; p is zero, 1 or 2; and R3 is hydrogen, a salt-forming cation or an ester-forming group; and the symbol &boxH;/&boxH; indicates that the double bond may be in either the E or Z configuration, or a pharmaceutically acceptable salt thereof, which comprises: a) reacting a compound of formula IV: R2â€”CHOâ€ƒâ€ƒ(IV) â€ƒwherein R2 is a fused bicyclic heterocyclic ring having the formula: wherein R4 and R5 are independently selected from the group consisting of hydrogen, (C1-6)alkanoyl, (C1-6)alkanoyloxy, amino, (C1-6)alkanoylamino, (mono or di)-(C1-6)alkylamino, hydroxy, (C1-6)alkoxy, sulpho, mercapto, (C1-6)alkylthio, (C1-6)alkylsulphinyl, (C1-6)alkylsulphonyl, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, halogen, carboxy, carboxy salts, carboxy esters, arylcarbonyl, and unsubstituted or substituted (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, and aryl(C1-6)alkyl groups; m is 2 or 3; and p is zero, 1 or 2; with a carbapenem of Formula (III): â€ƒwherein R1 and R3 are as described above and X is a halogen atom; in the presence of a base to form a compound of Formula (II): â€ƒwherein R1, R2 and R3 are as described above, X is a halogen atom and Z is a hydroxy group; b) followed by reductive elimination of the compound of Formula (II) to remove the X and Z groups to give a compound of Formula (I); and c) optionally preparing a pharmaceutically acceptable salt thereof.