A New Synthesis of Pteridines Substituted with Branched and Linear Alkenyl Groups at C(6). The Nitroso‐Ene Reaction of 4‐(Alkenoylamino)‐5‐nitrosopyrimidines

Abstract

Abstract Pteridines substituted with a 1,1‐, 1,2‐, or 1,1,3‐substituted alkenyl group (mostly ( E )‐configured) at C(6) were synthesized in high yields by the intramolecular nitroso‐ene reaction of 4‐(alkenoylamino)‐2‐amino‐6‐benzyloxy‐5‐nitroso‐ and 4‐(alkenoylamino)‐2,6‐diamino‐5‐nitrosopyrimidines. Thus, the N ‐alkenoyl nitrosopyrimidines 4 and 5 provided the pteridines 6 and 7 , respectively, characterized by a 1,2‐disubstituted ( E )‐alkenyl substituent, the C(4) ‐( E )‐geranoyl amide 13 led regio‐ and stereoselectively to the ( E )‐1,1,2‐trisubstituted alkenyl‐pteridine 16 , and the C(4) ‐( Z ) isomer 14 led to 17 possessing a 1,1‐disubstituted alkenyl group. The trifluoromethylated butenoyl amide 15 possessing a less highly nucleophilic alkenoyl group reacted more slowly to give the trifluoromethylated vinylpteridine 18 . Also the 4‐(alkenoylamino)‐2,6‐diamino‐5‐nitrosopyrimidine 20 reacted more slowly than 4 and 5 , and provided the pteridines 23 ; introduction of additional N ‐acyl groups as in 21 and 22 led to a considerably faster ene reaction. The X‐ray crystal structure analysis of the nitroso amide 15 shows eight symmetrically independent molecules in the unit cell. In the crystalline state, the N , N ‐dimethylformamidine derivative 9 of 6 forms a centrosymmetric dimer with the 7,8‐lactam group connected by intermolecular hydrogen bonds.