Saturated heterocycles. 254. synthesis and stereochemistry of saturated or partially saturated pyridazino‐[6,1‐b]‐ and phthalazino[1,2‐b]quinazolinones

Abstract

AbstractBy the reaction of anthranilic hydrazide 1 with cis‐2‐(p‐methylbenzoyl)‐1‐cyclohexanecarboxylic acid 2a or diendo‐3‐(p‐methylbenzoyl)bicyclo[2.2.1]heptane‐2‐carboxylic acid 2b, fused tetra‐ and pentacyclic ring systems 3a, b were prepared, trans‐2‐Amino‐1‐cyclohexanecar‐bohydrazide 4b was reacted with 3‐(p‐chlorobenzoyl)propionic acid 5 to yield the pyridazino[6,1‐b]quinazolinone 6. From the reaction of cis‐2‐amino‐1‐cyclohexanecarbohydrazide 4a with 2a, three isomeric partially saturated 8H‐phthalazino[1,2‐b]quinazolin‐8‐ones 7a‐c were formed. The reaction of diexo‐2‐aminobicyclo[2.2.1]heptane‐3‐carbohydrazide 4c and 2a furnished the pentacyclic derivatives 8 and 9 containing a 3‐aryl‐4,5‐dihydropyridazine or 3‐arylhexahydropyridazine ring C with cis annelated C/D rings. The formation of 8 and 9 involving different ring systems can be rationalized by two reaction pathways: (i) in the bislactam 9 the carboxyl group acylates the hydrazide, while (ii) in 8 it forms a pyridazine ring with the cyclic amino group by cyclocondensation. The structures of the products were elucidated by 1H and 13C nmr methods, including DEPT, DNOE and 2D‐HSC measurements.