Patent ID: 6437118
Filing Date: 2002-08-20
Classification: C07D,C07H,Y02P

Abstract:
A process for the preparation of a compound of formula I wherein R1 is hydrogen or COOR4 and R4 is (CH2)n-cycloalkyl wherein cycloalkyl consists of 3 to 6 carbon atoms and n is an integer from 0 to 4, heteroaryl-(lower alkyl), (lower-alkoxy)-(lower alkyl), aryloxy-(lower-alkyl), aralkyloxy-(lower-alkyl), (lower-alkylthio)-(lower-alkyl), arylthio-(lower-alkyl), aralkylthio-(lower-alkyl), oxo-(lower-alkyl), acylamino-(lower-alkyl), cyclic amino-(lower-alkyl), (2-oxocyclic amino)-(lower-alkyl) wherein the alkylene chain is unsubstituted or substituted with one or two lower alkyl groups; and R2 is hydrogen or a group of the formula (a) wherein Ra is hydrogen, a hydroxy protecting group or a group easily hydrolyzable under physiological conditions selected from acetyl, propionyl, benzoyl, toluoyl, glycyl, alanyl, &bgr;-alanyl, valyl and lysyl which comprises reacting a compound of the formula II wherein R21 is hydrogen or a group (a) wherein hydroxy groups are unprotected or protected, R3 is bromo, chloro or iodo, and R1 is hydrogen or a carboxylic ester group, with a vinyl borane compound of the formula IIIa or IIIb(CH2&boxH;CH)nB(R6)3âˆ’nLmâ€ƒâ€ƒ(IIIa) [(CH2&boxH;CH)pB(R6)4âˆ’p]X+â€ƒâ€ƒ(IIIb) whereinn is 1, 2 or 3; m is 0 or 1; R6 is hydrogen, halogen, alkyl, cycloalkyl, alkoxy, cycloalkoxy, hydroxy or aryl, and wherein, if more than one group R6 is present, these groups may be different from each other, or two groups R6 may, together with â€”Aâ€”(CH2)q-Y-(CH2)râ€”Aâ€”, form a carbocyclic or heterocyclic ring wherein A and Y are CH2 or NH or O and q and r are an integer from 0-4, or two groups R6 may also form a catechol moiety in whichR is hydrogen or lower alkyl; L is an amine, a Schiff base or an ether; p is 1, 2, 3 or 4; X+ is a cation; in the presence of a Pd complex and a base.