[4+2]-Cycloaddition of butyl vinyl ether to 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones

Reactions of 3-aroylpyrrolo[1,2-a]quinoxaline1,2,4(5H)-triones with alkoxyalkenes were not studied previously. By reacting 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones 1a and 1b with butyl vinyl ether in dioxane we obtained (1S*,16R*)-14-aryl-16-butoxy15-oxa-3,10-diazatetracyclo[8.7.0.0.0]heptadeca4,6,8,13-tetraene-2,11,12-triones 2a and 2b. The spectral parameters of compounds 2a and 2b were similar to those of their 3-oxa analogs, (1S*,16R*)-16-alkoxy14-aryl-3,15-dioxa-10-azatetracyclo[8.7.0.0.0]heptadeca-4,6,8,13-tetraene-2,11,12-triones [1], whose structure was proved by X-ray analysis. Cycloadducts 2a and 2b are formed via thermally ini t ia ted [4 + 2 ]-cycloaddi t ion involving the O=C–C=C conjugated bond system of triketones 1a and 1b and polarized C=C bond of butyl vinyl ether. Compounds 2a and 2b are heterocyclic analogs of 13(14→8)-abeosteroids, dankasterone [2] and abeohyousterone [3] which possess a rarely occurring fused carbocyclic skeleton and exhibit pronounced antitumor activity. 16-Butoxy-14-phenyl-15-oxa-3,10-diazatetracyclo[8.7.0.0.0]heptadeca-4,6,8,13-tetraene2,11,12-trione (2a). Butyl vinyl ether, 15.3 mmol, was added to a solution of 3.1 mmol of compound 1a in 10 mL of anhydrous 1,4-dioxane, and the mixture was heated for 40 min until the violet color typical of initial compound 1a disappeared. The mixture was cooled, and the yellow precipitate was filtered off. Yield 58%, mp 241–242°C (decomp., from THF). IR spectrum, ν, cm: 3193 (NH), 1694 (C=O, C=O, C=O). H NMR spectrum, δ, ppm: 0.83 t (3H, Me, J = 7 .3 Hz) , 1 .30 m (2 H, CH 2M e) , 1 .48 m (2 H, OCH2CH2), 2.28 d.d (1H, 17-H, J = 13.6, 4.8 Hz), 2.33 d.d (1H, 17-H, J = 13.6, 1.2 Hz), 3.64 m and 3.79 m (1H each, OCH2), 5.72 d.d (1H, 16-H, J = 4.8, 1.2 Hz), 7.10–7.93 m (9H, Harom), 10.93 s (1H, NH). C NMR spectrum, δC, ppm: 13.65 (Me), 18.44 (CH2Me), 31.01 (OCH2CH2), 36.40 (C), 55.70 (OCH2), 69.05 (C), 101.52 (C), 103.64 (C), 115.90– 132.98 (Carom), 159.49 (C), 163.81 (C), 166.86 (C), 176.20 (C). Found, %: C 68.75; H 5.27; N 6.48. C24H22N2O5. Calculated, %: C 68.89; H 5.30; N 6.69. 16-Butoxy-14-(4-chlorophenyl)-15-oxa-3,10-diazatetracyclo[8.7.0.0.0]heptadeca-4,6,8,13tetraene-2,11,12-trione (2b) was synthesized in a similar way. Yield 55%, mp 249–251°C (decomp., from dioxane). IR spectrum, ν, cm: 3190 (NH), 1698 (C=O, C=O, C=O). H NMR spectrum, δ, ppm: 0.83 t (3H, Me, J = 7.3 Hz), 1.30 m (2H, CH2Me), 1.47 m (2H, OCH2CH2), 2.28 d.d (1H, 17-H, J = 13.5, 4.8 Hz), 2.33 d.d (1H, 17-H, J = 13.6, 1.4 Hz), 3.64 m and 3.79 m (1H each, OCH2), 5.72 d.d (1H, 16-H, J = 4.8, 1.3 Hz), 7.10–7.95 m (8H, Harom), 10.94 s (1H, N H ) . F o u n d , % : C 6 3 . 7 2 ; H 4 . 8 7 ; N 6 . 2 5. C24H21ClN2O5. Calculated, %: C 63.65; H 4.67; N 6.19.