Patent ID: 7067666

Claim:
A method for the preparation of 7-substituted camptothecin compounds of formula (I) or (II): where X is H, NH 2 , OH, F, Cl, Br, O—C 1-6 alkyl, S—C 1-6 alkyl, NH—C 1-6 alkyl, N(C 1-6 alkyl) 2 , or C 1-8 alkyl, or X is -Z-(CH 2 ) a —N—(C 1-6 alkyl) 2 wherein Z is selected from the group consisting of O, NH and S, and a is an integer of 2 or 3, or X is —CH 2 NR 2 R 3 , where (a) R 2 and R 3 are, independently, hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy-C 1-6 COR 4 where R 4 is hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, or (b) R 2 and R 3 taken together with the nitrogen atom to which they are attached form a saturated 3-7 membered heterocyclic ring which may contain a O, S or NR 5 group, where R 5 is hydrogen, C 1-6 alkyl, alkyl, aryl, aryl substituted with one or more groups selected from the group consisting of C 1-6 alkyl, amino, C 1-6 alkylamino, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl C 1-6 alkyl C 1-6 alkoxy, aryl, and aryl substituted with one or more C 1-6 alkyl, or C 1-6 alkoxy-C 1-6 alkyl groups; R is C 1-30 alkyl, substituted C 1-30 alkyl, C 1-30 alkenyl, substituted C 1-30 alkenyl, C 1-30 alkynyl, substituted , C 1-30 alkynyl, C 3-30 cycloalkyl, substituted C 3-30 cycloalkyl, C 6-18 aryl, substituted C 6-18 aryl, C 6-18 aryalkyl, (C 1-30 alkyl) 3 silyl or (C 1-30 alkyl)i silyl C 1-30 alkyl, Y is independently H or F, and n is an integer of 1 or 2, and salts thereof comprising: i) reacting an ortho amino cyano aromatic compound of formula (III) or (IV) with an organometallic reagent R-M and ii) condensing a resulting product with a 20(S)tricyclic ketone of formula (VII)