Diels–Alder Additions, Ene Reactions, and Condensations of 4‐(Acylamino)‐5‐nitrosopyrimidines – Synthesis of 8‐Substituted Guanines and of 6‐Substituted Pteridinones

4‐(Acylamino)‐5‐nitrosopyrimidines react either by a reductive condensation to provide 8‐substituted guanines, or by a Diels–Alder cycloaddition, or an ene reaction, to provide 6‐substituted pteridinones, depending on the nature of the acyl group and the reaction conditions. Experimental details are provided for the transformation of (acylamino)‐nitrosopyrimidines to 8‐substituted guanines, and the scope of the reaction is further demonstrated by transforming the trifluoro acetamide 25 to the 8‐(trifluoromethyl)guanine ( 27 ), and the N,N ′ ‐ bis(nitrosopyrimidinyl)‐dicarboxamide 29 to the ( R , R) ‐1,2 ‐ di(guan‐8‐yl)ethane‐1,2‐diol ( 32 ). An intramolecular Diels–Alder reaction of the N ‐sorbyl (= N ‐hexa‐2,4‐dienoyl) nitrosopyrimidine 10 , followed by a spontaneous elimination to cleave the N,O bond of the initial cycloaddition product provided the pteridinones 14 or 15 , characterized by a ( Z )‐ or ( E )‐3‐hydroxyprop‐1‐enyl group at C(6). Treatment of 10 with Ph 3 P led to the C(8) ‐penta‐1,3‐dienyl‐guanine 18 . The ene reaction of the N ‐crotonyl (= N ‐but‐2‐enoyl) nitrosopyrimidine 19 provided the 6‐vinyl‐pteridinone 20a that dimerized readily to 21a , while treatment of 19 with Ph 3 P led in high yield to 8‐(prop‐1‐enyl)guanine ( 23 ). The structure of the dimer 21 was established by X‐ray analysis of its bis( N,N ‐dimethylformamidine) derivative 21b . The crystal structure of the nitroso amide 10 is characterized by two molecules in the centrosymmetric unit cell. Intermolecular H‐bonds connect the amino group to the amide carbonyl and to N(1). The crystalline bis(purine) 30 forms a left‐handed helix with four molecules per turn and a pitch of 30.2 Å.