A Facile Synthesis of 1-Monosubstituted and Unsymmetrically 1,3-Disubstituted Uracils

Synthesis and Antiviral Activity of 1,3-Disubstituted Uracils against HIV-1 and HCMV

“…We have already reported that the reaction of 2,4-dimethoxypyrimidine (3a) (Hilbert et al, 1930) with 2,6-difluorobenzyl bromide provided 1-alkyl-4-methoxy-2(1H)-pyrimidinone and subsequent treatment of the products with acid affords 1-(2,6difluorobenzyl)uracil (2c) (Maruyama et al, 1999). In the case of 1-cyanomethyluracil (2a), bis(trimethylsiloxy)pyrimidine (3b) was reacted with cyanomethyl chloride (Singh et al, 1980). Introduction of the second alkyl group was achieved by nucleophilic displacement of alkyl halide with uracil-3-anion, as typically illustrated in the case of 1cyanomethyl-3-(2-methylbenzyl)uracil (4a) (Grangier et al, 1994).…”

“…(4,6-Dimethylpyridin-2-yl)methanol and (2,6-dimethyl-pyridin-4-yl)-methanol were prepared by Pummerer reaction of 2,4,6-trimethylpyridine N-oxide (Syper et al, 1967). 1-Substituted uracils 2a-e were prepared by the method reported earlier (Ishikawa et al, 1991;Baker et al, 1967;Lazrek et al,1997;Maruyama et al, 1999;Singh et al, 1980). 1-Cyanomethyl-3-(2-methylbenzyl)uracil (4a).…”

Heterocalixarenes. 1. Calix[2]uracil[2]arene: Synthesis, X-ray Structure, Conformational Analysis, and Binding Character

“…An alternate two-step approach (path II, Scheme ), requiring selective N1 alkylation of uracil followed by subsequent cyclization of the intermediate product (Z) with the same or a different 1,3-bis(bromomethyl)benzene derivative, would provide calix[2]uracil[2]arene derivatives A or C selectively (Scheme ). Thus, 1,3-bis(trimethylsilyloxy)pyrimidine ( 1 ) on refluxing with 2a in 1,2-dichloroethane by using I 2 as catalyst provides 3a (60%), mp 268 °C, M + m / z 326. The cycloalkylation of 3a with 2a under phase-transfer catalytic conditions (K 2 CO 3 −CH 3 CN−tetrabutylammonium hydrogensulfate) provides 4a , a heterocalix[4]arene of type A (24%), mp 287−90 °C, M + m / z 428.…”

The Silyl Method for the Synthesis of 1[-2(Phenoxy)ethyl]uracils

“…For example, N (1) -substituted derivatives of uracil have been obtained by the condensation of 2,4-bis(trimethylsiloxy)pyrimidine with ethyl monobromoacetate and α-bromopropionate on boiling in dichloroethane in yields from 41 to 60% [8]. The reaction of 5-methyl-2,4-bis(trimethylsiloxy)pyrimidine with an excess of 1,4-dichlorobutane in methylene chloride at room temperature gave 1-(4-chloro-2-butyl)thymine in 47% yield [9].…”

“…[2-(phenoxy)ethyl]uracil(8).1 H NMR spectrum, δ, ppm (J, Hz): 3.98-4.20 (4H, m, CH 2 CH 2 ); 6.77-7.30 (5H, m, C 6 H 5 ); 8.06 (1H, s, H-6); 11.48 (1H, br. s, NH).…”