Patent ID: 6069248
Filing Date: 2000-05-30
Classification: C07D,C07F

Abstract:
A process for the synthesis of a compound of Formula A: ##STR16## wherein R.sup.1 represents H, alkyl, substituted alkyl, --OH, --OC.sub.1-4 alkyl, --N(C.sub.1-4 alkyl).sub.2, --C.sub.1-4 alkyl aryl, optionally substituted aryl, or an optionally substituted allyl;R.sup.2 and R.sup.3 independently at each occurance represent H, or a group selected from --C.sub.1 -C.sub.6 alkyl, --C.sub.3 -C.sub.6 cycloalkyl aryl, --C.sub.2-8 alkenyl, --C.sub.1-6 alkoxy, --C.sub.1-4 alkyl aryl, and aryl, said group optionally substituted with halogen, --C.sub.1-4 alkyl, --C.sub.1-4 alkoxy, allyl, heteroaryl, --SC.sub.1-4 alkyl, --OC.sub.1-4 alkyl, --N(C.sub.1-4 alkyl).sub.2, or benzyl;R.sup.4 represents H or R.sup.5 ;R.sup.5 represents C.sub.4-10 branched alkyl or cyclo alkyl, --C.sub.1-4 alkyl-N(R.sup.6).sub.2, --C.sub.2-6 alkynyl, halo substituted C.sub.1-10 alkyl, --C.sub.2-4 alkenyl, aryl, --C.sub.1-8 alkyl, heteroaryl, --C.sub.1-4 alkyl aryl, said --C.sub.1-8 alkyl, --C.sub.2-14 alkenyl, --C.sub.1-4 alkyl aryl, and aryl optionally substituted with one to tour substituents independently selected from a group consisting of halogen, --C.sub.1 -C.sub.6 alkyl, --C.sub.1-6 alkoxy, --CF.sub.3, --SC.sub.1-6 alkyl, P(O)(OCH.sub.3).sub.2, --S--(CH.sub.2).sub.0-4 aryl, --O--(CH.sub.2).sub.0-4 aryl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted heterocycloalkyl;R.sup.6 represents --C.sub.1-4 alkyl, phenyl, H, --C.sub.1-4 alkyl aryl, and heterocyclyl;X represents --OH, or --NH.sub.2 ;the process comprising:(a) reacting a compound of Formula 2SS--X Formula 2with a compound of Formula 3 ##STR17## in the presence of a coupling agent, wherein PG represents an amino protecting group;X, and R.sup.1 are as defined earlier,to yield a compound of Formula 4 ##STR18## wherein Y represents --NH--, or --O--; SS represents a solid support; andR.sup.1, and PG are as defined above;(b) treating a compound of Formula 4 with a deprotecting agent to yield a compound of Formula 5 ##STR19## wherein SS, Y, and R.sup.1 are as defined above; (c) reacting the compound of Formula 5 with a compound of Formula 6a ##STR20## or a compound of Formula 6b ##STR21## in the presence of a coupling agent, to yield a compound of Formula 7 ##STR22## or a compound of Formula 9 respectively ##STR23## wherein SS, Y, R.sup.1, R.sup.2, and R.sup.3 are as defined above; (d) reacting a compound of Formula 7 with a compound of Formula 8 ##STR24## to yield a compound of Formula 9 ##STR25## where SS, Y, R.sup.1, R.sup.2, and R.sup.3 are as defined above; (e) reacting the compound of Formula 9 with a compound of Formula 10 ##STR26## to yield a compound of Formula 11 ##STR27## where SS, Y, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined above; (f) optionally alkylating a compound of Formula 11, wherein R.sup.4 is H, with a compound of Formula 12R.sup.5 --OH Formula 12to yield a compound of Formula 11, wherein R.sup.4 is R.sup.5 ; and(g) treating a compound of Formula 11 with a cleaving agent to yield compound of Formula A.