REGIOSELECTIVE CCI-779 SYNTHESIS Russian patent published in 2008 - IPC C07D498/22 C07F5/02 

FIELD: chemistry.

SUBSTANCE: regioselective synthesis of complex rapamycin 42-ether (CCI-779) involves: (a) acylation of 31-silyl rapamycin ether by compound of formula HOOC.CR⁷R⁸R⁹ or its combined anhydride, where: R⁷ is hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 2-7 carbon atoms, alkinyl with 2-7 carbon atoms, -(CR¹²R¹³)_fOR¹⁰, -CF₃, -F or -CO₂R¹⁰; R¹⁰ is hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 2-7 carbon atoms, alkinyl with 2-7 carbon atoms, triphenylmethyl, benzyl, alcoxymethyl with 2-7 carbon atoms, chloroethyl or tetrahydropyranyl; R⁸ and R⁹ together form X; X is 2-phenyl-1,3,2-dioxaborinane-5-yl or 2-phenyl-1,3,2-dioxaborinane-4-yl, where phenyl can be optionally substituted; R¹² and R¹³ each is independently hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 2-7 carbon atoms, alkinyl with 2-7 carbon atoms, trifluormethyl or -F; and f=0-6; to obtain 42-ether boronate of 31-silyl rapamycin ether; (b) selective hydrolysis of 42-ether boronate of 31-silyl rapamycin ether in moderately acid environment to obtain rapamycin 42-ether boronate; and (c) diol treatment of rapamycin 42-etherboronate to obtain complex rapamycine 42-ether. Invention also claims new intermediate products applicable in this method.

EFFECT: application as antitumour medication.

48 cl, 3 ex