Synthesis of indol condensed derivatives of pyrido[1,2-a]pyrimidines

A series of 7,1 2dihydro-pyrimido[1',2';1,2]pyrido[3,4-b]indol-4-(6H)-ones was prepared by Fischer indolization of 9-aryl-hydrazono-6,7,8,9-tetrahydro -4H-pyrido[1,2-a]pyrimidin-4-ones. Quantumchemical calculations (ab initio and AMI) indicate that position 3 of 7,12-dihydro-pyrimido[1',2';1,2] pyrid o[3,4-b]indol-4(6H)-one can be involved in electrophilic substitutions, whi le position 2 is sensitive towards nucleophilic attack. Bromination of 6-me thyl- 7,12-dihydro- pyrimido[1 ',2';1,2]pyrido[3,4-b] indol-4(6H)-one (16) with bromine afforded 3-bromo derivative (25), which was reacted with cycli c 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. Vilsmeier-Haack fo rmylation of compound (16) give 12-formyl (31) and 3,12-diformyl (32) deriv atives tan N-formyl-1-aza derivative (34) of nauclefidine alkaloid (1) at 6 0 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 in some cas es by C-13 ruler, CD spectra and X-ray investigations.