Patent ID: 6175009
Filing Date: 2001-01-16
Classification: C07D

Abstract:
A process for the preparation of a compound of formula (I): ##STR41##wherein:R.sup.1 is C.sub.1-3 alkyl substituted with 1-7 halogen;R.sup.2 is selected from C.sub.1-5 alkyl substituted with 1-2 R.sup.4, C.sub.2-5 alkenyl substituted with 1-2 R.sup.4, C.sub.2-5 alkynyl substituted with 1 R.sup.4, and OR.sup.2a ;R.sup.2a is C.sub.1-4 alkyl;R.sup.3a is H;R.sup.3b is selected from H, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, F, Cl, Br, I, and NR.sup.5 R.sup.5a ;R.sup.3c is selected from H, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, F, Cl, Br, I, and NR.sup.5 R.sup.5a ;R.sup.3d is selected from H, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, F, Cl, Br, I, and NR.sup.5 R.sup.5a ;alternatively, R.sup.3a and R.sup.3b combine to form --OCH.sub.2 O--;R.sup.4 is selected from C.sub.3-5 cycloalkyl substituted with 0-2 R.sup.4a, phenyl substituted with 0-5 R.sup.4a, and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R.sup.4a ;R.sup.4a is selected from C.sub.1-3 alkyl, Cl, Br, F, I, OCH.sub.3, SCH.sub.3, and NR.sup.5 R.sup.5a ; andR.sup.5 and R.sup.5a are independently selected from H and C.sub.1-3 alkyl;the process comprising:step (1), contacting a compound of formula (II): ##STR42##or a salt form or a hydrate of the salt form thereof;with an isocyanate of formula (III): ##STR43##wherein:R.sup.8a is selected from methyl, ethyl, propyl, and isopropyl;R.sup.8 is selected from phenyl substituted with 0-3 R.sup.9, and naphthyl substituted with 0-3 R.sup.9 ; andR.sup.9 is selected from C.sub.1-4 alkyl, C.sub.1-4 alkoxy, F, Cl, Br, and I;to form a compound of formula (II-a): ##STR44##or a salt form thereof;step (1-i), cyclizing the compound of formula (II-a) to form a compound of formula (IV): ##STR45##step (2), dehydrating the compound of formula (IV) to form a compound of formula (V): ##STR46##step (2-i), contacting the compound of formula (V) with a nucleophile of formula (VI):R.sup.2 --M (VI)wherein M is a metal counterion;to form a compound of formula (VII): ##STR47##or a salt form thereof; andstep (3), ionizing the compound of formula (VII) to form a compound of formula (I), or a pharmaceutically acceptable salt form thereof.