Cyclization of 2-amino-6-bromo-4-oxochromene-3-carboxamide (5) with diethyl oxalate-sodium ethoxide gave the benzopyrano [ 2,341 pyrimidine-4,6-dione (6). Ethyl 3-amino-2-carbamoyl-4-0x0-chromene-6-carboxylate (10a) in a similar reaction gave derivatives of a novel ring system benzopyra no [ 3,2 -d ] pyrimidine (8) but when 3 -amino -4 -oxoc h romene-2 -carboxamide (1 Ob) was subjected to the same reaction, the novel ring system benzopyrano[3,2-e] -1,4-diazepine (14a) was obtained in high yield. This structure, which contains the hitherto unknown 1,4-diazepine-2,3,5-trione ring, is supported by spectroscopic and chemical evidence. The presence of a 3-amino and a 2-carbonyl group in a chromone has an unexpected shielding effect on the chemical shift of C-8. The course of the cyclization was studied. Attempts to cycl ize 3-am i nomet hy 1-4-oxoc hromene-2 -carboxam ide (28; X = Y = H), a homologue of (lob), failed but a new ring system (31) was obtained when ethyl 3-bromo-4-oxochromene-2-carboxylate (29; R' = OEt) reacted with o-phenylenediamine.A number of chromones in which a third heterocyclic ring is fused at the 2,3-bond have recently been described.2 Pyridine, pyrrole, 1,2,3-triazole, 1,2-, 1,4-, and 1,5-diazepine rings have been fused to chromone in this way; several of these were formed from functional groups at C-2 and C-3 of the chromone and some of the products possessed pharmacological properties. We now describe the synthesis of several other new ring systems and related compounds.
( 2 )Anthranilamides are readily cyclized by reaction with various reagents to give quinazoline~.~ For example, Nakanishi and Massett obtained high yields of 4-oxoquinazoline-2-carboxylic acid derivatives (2; X = CH) by heating anthranilamide (1; X = CH) with diethyl oxalate and sodium ethoxide. Heterocyclic analogues of anthranilamide gave similar products (2; X = N). Cyclizations of this type do not appear to have been attempted in the chromone series although suitable precursors,
3-amino-4-oxochromene-2-carboxamide '9'and 2-amino-4-oxochromene-3-carboxamide have been available for some time. In order to prepare 2-amino-6-bromo-4-oxochromene-3-carboxamide (5), we cyclized 2-acetoxy-5-bromobenzoyl chloride (3; R = Br) by reaction with malononitrile and sodium h y d r~x i d e .~The product, 2-amino-6-bromo-4-oxochromene-3-carbonitrile ( 4 R = Br) was converted into the 3-carboxamide (5). When Nakanishi and Massett's method was applied to this amino carboxamide, ethyl 7-bromo-4,5-dioxo-3H-[ 11 benzopyrano[2,3,-d]pyrimidine-2-carboxylate (6; R = Br) was formed in moderate yield. The amino nitrile (4; R = H ) 7 was converted into the tricyclic ester ( 6 R = H) by successive acylation with ethoxalyl chloride [which first yielded the carboxamide (7; R = H)] and thermal cyclization to the pyrimidine (6; R = H). The latter procedure gave a better yield than that using hydrogen chloride-ethanol.Derivatives of the novel isomeric ring system, [ llbenzopyrano[3,2-d]pyrimidine (8) have been synthesized by applying the method described a...
