Pyrrolo [2, 1-c] [1, 4] benzodiazepine-anthraquinone conjugates useful as antitumour agents

A process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepines of formula V wherein n is 3-4 and R is H, OH,

• the process comprising:
• (a) reacting N-(9,10-dihydro-9,10-dioxo-1-anthracenyl)-1-bromo-alkanamide of formula I with (2S)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl thioacetal of formula II in an aprotic water miscible organic solvent in the presence of a mild inorganic base
• and isolating 2S-N-{4[N-(9,10-dihydro-9,10-dioxo-1-anthracenyl)-alkane-3-carboxamide]-oxy-5-methoxy-2-nitrobenzoyl} pyrrolidine-2-carbaxaldehyde diethyl thioacetal of formula III so obtained;
• (b) reducing the thioacetal of formula III in presence of organic solvent and isolating 2S-N-{4-[N-(9,10-dihydro-9,10-dioxo-1-anthracenyl)-alkane-3-carboxamide]-oxy-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carbaxaldehyde diethyl thioacetal of formula IV so obtained;
• (c) reacting the amino thioacetal of formula IV with a deprotecting agent to give the pyrrol[2,1-c][1,4]benzodiazepine of formula V wherein n and R are as stated above.