Claims for Patent: RE46965

Summary for Patent: RE46965

Title:	Intermediates for the preparation of analogs of Halichondrin B
Abstract:	The present invention provides macrocyclic compounds, synthesis of the same and intermediates thereto. Such compounds, and compositions thereof, are useful for treating or preventing proliferative disorders Formula (F-4).
Inventor(s):	Brian Austad, Charles E. Chase, Francis G. Fang, Trevor Calkins, Bryan M. Lewis
Assignee:	Eisai R&D Management Co Ltd
Application Number:	US13/924,892
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE46965
Patent Claims:	1. A compound of formula F-4: wherein: each of PG1, PG2, and PG3 is independently hydrogen or a suitable hydroxyl protecting group; R1 is R or —OR; each R is independently hydrogen, C1-4 haloaliphatic, benzyl, or C1-4 aliphatic; and LG1 is a suitable leaving group. 2. The compound according to claim 1, wherein said compound is of formula F-4′: 3. The compound according to claim 2, wherein R1 is OR wherein R is hydrogen, methyl, or benzyl. 4. The compound according to claim 2, wherein PG1 and PG2 are both hydrogen. 5. The compound according to claim 2, wherein each of PG1 and PG2 is independently a suitable hydroxyl protecting group. 6. The compound according to claim 5, wherein one or both of PG1 and PG2, taken together with the oxygen atom to which each is bound, is a silyl ether or an arylalkyl ether. 7. The compound according to claim 6, wherein PG1 and PG2 are both t-butyldimethylsilyl. 8. The compound according to claim 5, wherein PG1 and PG2 are taken together, with the oxygen atoms to which they are bound, to form a diol protecting group. 9. The compound according to claim 8, wherein said diol protecting group is a cyclic acetal or ketal, a silylene derivative, a cyclic carbonate, or a cyclic boronate. 10. The compound according to claim 2, wherein LG1 is sulphonyloxy, optionally substituted alkylsulphonyloxy, optionally substituted alkenylsulfonyloxy, optionally substituted arylsulfonyloxy, or halogen. 11. The compound according to claim 10, wherein LG1 is mesyloxy tosyloxy, chloro, iodo, bromo, or triflate. 12. The compound according to claim 2, wherein said compound is: 13. The compound according to claim 1, wherein said suitable hydroxyl protecting group, taken with the oxygen atom to which it is bound, is selected from an ester, an ether, a silyl ether, an alkyl ether, an arylalkyl ether, and an alkoxyalkyl ether. 14. The compound according to claim 13, wherein said ester is a formate, acetate, carbonate, or sulfonate; said silyl ether is a trialkylsilyl ether; or said alkoxyalkyl ether is an acetal. 15. The compound according to claim 13, wherein said ester is formate, benzoyl formate, chloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate, 4,4-(ethylenedithio)pentanoate, pivaloate (trimethylacetyl), crotonate, 4-methoxy-crotonate, benzoate, p-benzylbenzoate, 2,4,6-trimethylbenzoate, methyl carbonate, 9-fluorenylmethyl carbonate, ethyl carbonate, 2,2,2-trichloroethyl carbonate, 2-(trimethylsilyl)ethyl carbonate, 2-(phenylsulfonyl)ethyl carbonate, vinyl carbonate, ally! carbonate, or p-nitrobenzyl carbonate; said silyl ether is trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, or triisopropylsilyl ether; said alkyl ether is methyl, trityl, t-butyl, allyl, or allyloxycarbonyl ether; said alkoxyalkyl ether is methoxymethyl, methylthiomethyl, (2-methoxyethoxy)methyl, benzyloxymethyl, beta-(trimethylsilyl)ethoxymethyl, and tetrahydropyranyl ethers; or said arylalkyl ether is benzyl, p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, 2- picolyl, or 4-picolyl. 16. The compound according to claim 1, wherein LG1 is mesyloxy or tosyloxy. 17. The compound according to claim 9, wherein said cyclic acetal or ketal is methylene, ethylidene, benzylidene, isopropylidene, cyclohexylidene, or cyclopentylidene; or said silylene derivative is di-t-butylsilylene or a 1,1,3,3-tetraisopropyldisiloxanylidene derivative. 18. The compound according to claim 1, wherein LG1 is sulphonyloxy, optionally substituted alkylsulphonyloxy, optionally substituted alkenylsulfonyloxy, optionally substituted arylsulfonyloxy, or halogen. 19. A compound of formula: and/or a pharmaceutically acceptable salt thereof. 20. A composition comprising a compound: and/or a pharmaceutically acceptable salt thereof, and a compound of formula: and/or a pharmaceutically acceptable salt thereof.