A new strategy for automated solid phase synthesis of an oligonucleotide conjugate of the base sensitive anti-cancer agent mitozolomide is described. Fully protected oligonucleotides were selected as base sensitive model sequences and were synthesized in 99% overall yields using a novel silyl-linked controlled-pore glass (SLCPG) solid support. Quantitative cleavage of compounds from SLCPG was achieved within 60 s at room temperature using tetra-n-butylammonium fluoride (TBAF) buffered with acetic acid. Reversed-phase HPLC analysis of lipophilic compounds 5 and 8 showed distributions of diastereoisomers due to chirality at the protected phosphorus centres. Pentyl-linked mitozolomide phosphoramidite, prepared in three steps from mitozolomide in 35% overall yield, was used in solid phase synthesis of a mitozolomide-oligonucleotide conjugate. Cleavage of the conjugate from SLCPG and concomitant removal of the cyanoethyl groups from phosphorus was achieved within 2 h at 50°C using TBAF buffered with acetic acid.