Patent ID: 6150530
Filing Date: 2000-11-21
Classification: A61K,A61P,C07C,C07D,C07K

Abstract:
A process for the preparation of a compound of the formula: ##STR18## wherein R.sub.1 is monosubstituted thiazolyl, monosubstituted oxazolyl, monosubstituted isoxazolyl or monosubstituted isothiazolyl wherein the substituent is selected from (i) C.sub.1 - to -C.sub.6 -loweralkyl, (ii) C.sub.1 -to -C.sub.6 -loweralkenyl, (iii) C.sub.3 - to -C.sub.7 -cycloalkyl, (iv) C.sub.3 - to -C.sub.7 -cycloalkyl -C.sub.1 - to -C.sub.6 -alkyl, (v) C.sub.5 - to -C.sub.7 -cycloalkenyl, (vi) C.sub.5 - to -C.sub.7 -cycloalkenyl -C.sub.1 - to -C.sub.6 -alkyl, (vii) C.sub.1 - to -C.sub.6 -alkoxy -C.sub.1 - to -C.sub.6 -alkyl or benzyloxy -C.sub.1 - to -C.sub.6 -alkyl, (viii) C.sub.1 - to -C.sub.6 -thioalkoxy -C.sub.1 - to -C.sub.6 -alkyl or benzyl-S-C.sub.1 - to -C.sub.6 -alkyl, (ix) C.sub.1 - to -C.sub.6 -alkylamino, (x) di-C.sub.1 - to -C.sub.6 -alkylamino, (xi) phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from halo, C.sub.1 - to -C.sub.6 -loweralkyl, hydroxy, C.sub.1 - to -C.sub.6 -alkoxy, benzyloxy, -S-benzyl and C.sub.1 - to -C.sub.6 -thioalkoxy, (xii) phenyl -C.sub.1 - to -C.sub.6 -alkyl wherein the phenyl ring is unsubstituted or substituted as defined above, (xiii) di -C.sub.1 - to -C.sub.6 -alkylamino -C.sub.1 - to -C.sub.6 -alkyl, (xiv) C.sub.1 - to -C.sub.6 -alkoxy or benzyloxy and (xv) C.sub.1 - to -C.sub.6 -thioalkoxy or -S-benzyl;n is 1, 2 or 3;R.sub.2 is hydrogen or C.sub.1 - to -C.sub.6 -loweralkyl;R.sub.3 is C.sub.1 - to -C.sub.6 -loweralkyl;R.sub.4 and R.sub.4a are independently selected from phenyl, thiazolyl and oxazolyl wherein the phenyl, thiazolyl or oxazolyl ring is unsubstituted or substituted with a substituent selected from (i) halo, (ii) C.sub.1 - to -C.sub.6 -loweralkyl, (iii) hydroxy, (iv) C.sub.1 - to -C.sub.6 -alkoxy or benzyloxy and (v) C.sub.1 - to -C.sub.6 -thioalkoxy or -S-benzyl;R.sub.6 is hydrogen or C.sub.1 - to -C.sub.6 -loweralkyl;R.sub.7 is thiazolyl, oxazolyl, isoxazolyl or isothiazolyl wherein the thiazolyl, oxazolyl, isoxazolyl or isothiazolyl ring is unsubstituted or substituted with C.sub.1 - to -C.sub.6 -loweralkyl; andZ is absent, --O--, --S--, --CH.sub.2 -- or --N(R.sub.8)-- wherein R.sub.8 is C.sub.1 - to -C.sub.6 -loweralkyl, C.sub.3 - to -C.sub.7 -cycloalkyl, --OH or --NHR.sub.8a wherein R.sub.8a is hydrogen or C.sub.1 - to -C.sub.6 -loweralkyl; or a pharmaceutically acceptable salt thereof, comprising reaction of a compound of the formula: ##STR19## or a salt thereof wherein R.sub.4, R.sub.4a, R.sub.6 and R.sub.7 are as defined above with an activated ester derivative of a compound of the formula: ##STR20## wherein R.sub.1, R.sub.2, R.sub.3, Z and n are as defined above.