Patent ID: 6800785
Filing Date: 2004-10-05
Classification: C07C

Abstract:
A process for making compounds of formula I: comprising the steps of:a. alkylating an indanone of formula II to yield an intermediate of formula III; b. adding a nucleophile to the intermediate of formula III to yield a diene of formula IV; c. cyclizing the diene of formula IV via a ring closing olefin metathesis reaction to yield an allylic alcohol of formula V; d. rearranging the compound of formula V via an allylic oxidative rearrangement to yield an en one of formula VI; e. optionally deprotecting R3; wherein R1 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, (cycloalkyl)alkyl, aryl, heteroaryl, arylalkyl, (heteroaryl)alkyl or SiRaRbRc wherein said alkyl, cycloalkyl, aryl and heteroaryl groups are optionally substituted with 1, 2 or 3 groups selected from fluoro, chloro, bromo, iodo, ORd, NReRf, O(C&boxH;O)NReRf, NRe(C&boxH;O)Rf, NRe(C&boxH;O)ORf, SRe, S(O)Re, SO2Re, SO2NReRf, LRg or MLRg; R2 is hydrogen, fluoro, chloro, bromo, iodo, methyl or CF3; R3 is hydrogen, C1-10 alkyl, benzyl or a removable hydroxyl protecting group; R4 is hydrogen, fluoro, chloro, bromo, iodo, methyl or CF3; R5 is hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-6 cycloalkyl, (cycloalkyl)alkyl, aryl, heteroaryl, arylalkyl or (hetereoaryl)alkyl wherein said alkyl, alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, aryl, heteroaryl, arylalkyl and (heteroaryl)alkyl groups are optionally substituted with bromo, iodo, ORd, SRe, 1-3 C1-3alkyl, 1-3 chloro or 1-5 fluoro; Ra, Rb, and Rc are independently selected from C1-8alkyl, O(C1-8alkyl) and phenyl; Rd is a removable hydroxyl protecting group, C1-10alkyl, benzyl or phenyl, wherein said phenyl group is optionally substituted with 1-3 substituents independently selected from C1-4alkyl, O(C1-4alkyl), NH(C1-4alkyl), N(C1-4alkyl)2, or halo; Re is C1-10alkyl or phenyl, wherein said alkyl group is optionally substituted with a group selected from O(C1-4alkyl), NH(C1-4alkyl), N(C1-4alkyl)2, phenyl or 1-5 fluoro, and wherein said phenyl group is optionally substituted with 1-3 substituents independently selected from C1-4alkyl, O(C1-4alkyl), NH(C1-4alkyl), N(C1-4alkyl)2 or halo; Rf is C1-10alkyl or phenyl, wherein said phenyl group is substituted with 1-3 substituents independently selected from C1-4alkyl, O(C1-4alkyl), NH(C1-4alkyl), N(C1-4alkyl)2 or halo; or Re and Rf, whether or not on the same atom, can be taken together with any attached and intervening atoms to form a 4-7 membered ring; Rg is NReRf, ORd, NRe(C&boxH;O)Rf, CONReRf, SO2NReRf or a 4-9 membered mono- or bicyclic N-heterocycloalkyl ring that can be optonally substituted with 1-3 C1-3 alkyl and can be optionally interrupted by O, S or NRe; L is CH2, CReRf, or C2-6 alkylene, wherein said alkylene linker can be optionally interrupted by O, S or NRe; M is O, S, NRe, NRe(C&boxH;O) or (C&boxH;O)NRe; and n is one, two or three.