Patent ID: 6649778
Filing Date: 2003-11-18
Classification: A61P,C07D

Abstract:
A method of preparing a 2â€²-substituted taxane, comprising:a) reacting a taxane of the formula (I) â€ƒwherein: R1 is selected from the group consisting of phenyl, t-butoxy, isopropyloxy, propyloxy, â€”C(CH3)&boxH;CHâ€”CH3, 2-naphthyl, 4-hydroxyphenyl, 4-methoxyphenyl, 4-fluorophenyl, 2-methyl-1-propenyl, cyclopropyl, 3-furanyl, 3-thioethyl and 2-propenyl; R2 is selected from the group consisting of acetyl, â€”CH3, â€”CH2CH3 and â€”CHO; R3 is selected from the group consisting of acetyl, H and C1-6 alkyl; R4 is selected from among H, F, C1-6 alkyl, â€”C(O)â€”CH2CH2CH2CH2CH3, â€”CH2SCH3, â€”SiEt3, â€”CH2OP(O)(OCH2Ph)2, CH3CH2C(O)â€”, â€”CH2O(CO)CH2N(CH2CH2)2NCH3, â€”CH2O(CO)CH2N(CH2CH3)2, â€”C(O)CH2N(CH3)2, â€”C(O)CH(CH3)NHCOOC(CH3)3; and R5 is selected from the group consisting of phenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-fluorophenyl, 4-triflourotoluene, 2-furanyl, 2-thienyl, phenylethene, 2-furanyl-CH&boxH;CHâ€”, (CH3)2CHCH2â€”, C6H11â€”CH2â€”, (CH3)2CHâ€”, PhCH2CH2â€”, C6HIIâ€”CH2CH2â€”, CH3CH2CH2â€”, 4â€”Cl-phenyl-, 2-fluorophenyl-, 3-fluoro-phenyl- and 4â€”CH3-phenyl- with a compound of formula (II) â€ƒwherein: E is a member of the group consisting of L1 is a bifunctional group; Y1 is selected from among O, S or NR7; R6 and R7 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-19 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy and C1-6 heteroalkoxy; and J1 is selected from the group consisting of OH and leaving groups; under conditions sufficient to form a blocked intermediate of the formula (III) b) deprotecting said blocked intermediate with about an equimolar amount of a secondary amine under conditions sufficient to form a compound of formula (IV):