Patent ID: 6566542
Filing Date: 2003-05-20
Classification: A61P,C07J

Abstract:
A process for the preparation of a compound selected from the group consisting of a compound of the formula wherein R1 is selected from the group consisting of hydrogen, â€”(CH2)mâ€”Ar, â€”(CO)â€”Ar, â€”(CH2)mâ€”Alk and â€”(CO)-Alk, R2 is unsaturated or saturated hydrocarbon of up to 6 carbon atoms, X is halogen, Y is selected from the group consisting of â€”Oâ€”, â€”Sâ€”, â€”NHâ€”, â€”SOâ€”, â€”SO2â€” and a single bond, Z is hydrogen or halogen, n is an integer from 2 to 5, R3 and R4 are individually selected from the group consisting of hydrogen, â€”(CH2)mâ€²â€”Ar, â€”(CH2)mâ€²â€”Het and â€”(CH2)mâ€²â€”Alk or taken together with the nitrogen to which they are attached form an unsaturated or saturated, aromatic or non-aromatic mono- or polycyclic heterocycle of 3 to 15 members optionally containing 1 to 3 additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen unsubstituted or substituted, Ar is a carbocyclic aryl of 6 to 18 carbon atoms, Het is unsaturated or saturated, aromatic or non-aromatic heterocycle of 1 to 9 carbon atoms and 1 to 5 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, Alk is saturated or unsaturated alkyl or cycloalkyl of up to 12 carbon atoms, m and mâ€² are integers from 0 to 3, the dotted line indicates a possible second bond, the Ar, Het and Alk being unsubstituted or substituted with at least one member of the group consisting of halogen, alkoxy, alkylthio, â€”NH2, mono- and dialkylamino optionally oxidized, aminoalkyl, dialkylaminoalkyl, â€”OH, acyloxy, acyl, carboxy, alkoxy carbonyl, â€”CN, â€”CF3, aryl, aralkyl and alkyl, alkenyl and alkyl unsubstituted or substituted by a member of the group consisting of halogen, alkyl, alkoxy, alkylthio, â€”NH2 and mono- and dialkylamino and its non-toxic, pharmaceutically acceptable acid and base salts, comprising reacting a compound of the formula: wherein R2 and Z are as defined above, RA is selected from the group consisting of: wherein Y, n, R3 and R4 are as defined above and Hal is halogen, if appropriate after protection and/or activation of the OH functions, either a) with a reducing agent of the keto in position 17 to obtain a compound of the formula: b) then with a halogenation agent to obtain a compound of the formula: corresponding to certain compounds of formula (I), when RA is â€”Phâ€”Yâ€” (CH2)nâ€”NR3R4, or a) with a hydrazine to obtain a compound of the formula: b) then with a halogenation agent to obtain a compound of the formula: corresponding to a certain compounds of formula (I), when RA is â€”Phâ€”Yâ€”(CH2)nâ€”NR3R4, the compounds of formula (II), (IIIa), (IIIb), (Iâ€²a) or (Iâ€²b), in protected or unprotected form, are subjected, if desired, to at least one of the following reactions: deprotection of any protected OH, acylation/alkylation of any OH, the action of HNR3R4, optionally in the form of a salt, when RA is â€”Phâ€”Yâ€”(CH2)nâ€”Hal or activated â€”Phâ€”Yâ€”(CH2)nâ€”OH, and salification.