Adibendan
Adibendan is an inhibitor of phosphodiesterase 3. It has been tested in dogs for its effects on heart output and dilation of blood vessels.
Synthesis
Synthesis: Patent :N-benzyloxindole is the starting material. Base facilitated alkylation with 2 molar equivalents of methyl halide gives 1-benzyl-3,3-dimethylindol-2-one, PC11086219. Dissolving metal reduction was the reaction medium which was employed to cleave the benzyl protecting group to give 3,3-dimethyloxindole . Nitration of this can obviously be achieved by the nitronium ion to give 3,3-dimethyl-5-nitro-oxindole . Catalytic hydrogenation over palladium then reduces the nitro group to give 3,3-dimethyl-5-amino-oxindole . Treatment with acetic anhydride protects amino groups as the acetamide. Treatment with nitric acid is then able to add a nitro group on to the aromatic ring which is probably sterically directed. Treatment with acid hydrolyses the acetamide protecting groups to give 3,3-dimethyl-5-amino-6-nitro-oxindole, PC22162178. Catalytic hydrogenation over platinum oxide reduces the nitro group to give 3,3-dimethyl-5,6-diamino-oxindole . The last step of the reaction sequence is a condensation with Isonicotinaldehyde, thus completing the synthesis of adibendan, respectively.