Synthesis and reactivity of debenzorutaecarpine derivatives]

A series of 7,12-dihydropyrimido[1',2';1,2]pyrido[3,4-b]indol-4(6H)-ones was prepared by Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one s. Quantumchemical calculations (ab initio and AM1) indicate that position 3 of 7,12-dihydro-pyrimido[1',2';1,2]pyrido[3,4-b]indol-4(6H)-one can be involved in electrophilic substitutions, while position 2 is sensitive towards nucleophilic attack. Bromination of 6-methyl-7,12-dihydropyrimido[1',2';1,2]pyrido[3,4-b]indol-4(6H)-o ne (16) with bromine afforded 3-bromo derivative (25), which was reacted with cyclic amines to give 2-amino-7,12-dihydro-pyrimido[1',2';1,2]pyrido[3,4-b]indol-4(6H)-ones (26-30) in an addition-elimination reaction. Vielsmeier-Haack formylation of compound (16) give 12-formyl (31) and 3,12-diformyl (32) derivatives (an N-formyl-1-aza derivative of nauclefidine alkaloid (34) at 60 degrees C and 100 degrees C, respectively. 3,12-dformyl compound (32) was oxidized to 3-carboxyl derivative (33). The quaternary salt (35), obtained from compound (16) with dimethyl sulphate, suffered a ring opening on the action of aqueous sodium hydroxide. The new compounds have been characterized by elemental analyses uv, 1H nmr and in some cases by 13C ruler, CD spectra and X-ray investigations.