Researches on Pyrimidines. CLIX. Synthesis of 6-Benzyl- and 5-Benzyluracils¹

Novel synthetic route for 5‐substituted 6‐arylmethylluracils from 2,4,6‐trichloropyrimidines

“…The intermediates i were decarboxylated in strong acidic medium to afford 6‐arylpyrimidine‐2,4‐diols ii which are the enol forms of compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h (Scheme ). Compounds 5a,b,f have previously been prepared through desulfurization of the corresponding 2‐thiouracil derivatives [14–16]. Compounds 5a , 5b , 5c , 5d were brominated with N ‐bromosuccinimide in absolute ethanol in the presence of benzoyl peroxide at room temperature to give the 5‐bromouracil derivatives 6a , 6b , 6c , 6d (Scheme ).…”

“…5‐Bromo‐6‐arylmethyluracils were used as inhibitors of thymidine phosphorylase [11–13]. Uracil derivatives are known to be synthesized by refluxing the corresponding thiouracils with 10% aqueous chloroacetic acid [14–21]. Thiouracils are synthesized by the condensation of the appropriate β‐ketoester with thiourea in strong basic medium [14–21].…”

“…Uracil derivatives are known to be synthesized by refluxing the corresponding thiouracils with 10% aqueous chloroacetic acid [14–21]. Thiouracils are synthesized by the condensation of the appropriate β‐ketoester with thiourea in strong basic medium [14–21]. Lee and Kim [22] have reported the synthesis of 5‐alkyl‐6‐benzyluracil derivatives by the reaction of 5‐alkyl‐2,4,6‐trichloropyrimidines with various arylmethyl magnesium halides to afford the regioselectively 6‐arylmethyl‐2,4‐dichloropyrimidines as the major products.…”

Synthesis and anti‐HIV‐1 activity of 1,3‐phenylene bis‐uracil analogues of MKC‐442

“…Compound 2 was used as the starting material for the synthesis of the bisthiouracil 4 in a ring closure reaction with thiourea and sodium ethoxide using the method of Danel et al [6] to afford this compound as the major product in 42% yield and 2-thio-pyrimidine-benzylic-β-ketoester 5 as minor product in 18% yield. Desulphurization of 4 using chloroacetic acid [7,8] gave the benzylic bis-uracil 6 in 63% yield (Scheme 1). Compound 6 was silylated using bis-(trimethylsilyl)-acetamide (BSA) and it was subsequently N-1 alkylated using chloromethyl ethyl ether [7] to give the bis-nonnucleoside analogues 7 in 23% yield and the N-1 monoalkylated by-product 8 in 11% yield.…”

Synthesis of Furoannelated Analogues of Emivirine (MKC‐442)

“…6-Benzyluracil was prepared according to Johnson and Ambelang [12], and its 5-hydroxymethylation to afford 4 was carried out as described by Petersen et al [13]. However, 4 was insoluble in benzene, the solvent used for the subsequent radical ring closure reaction.…”