6‐(Diazomethyl)‐1,3‐bis(methoxymethyl)uracil, Synthesis and Transformation into Annulated Pyrimidinediones

Abstract

6-(Diazomethyl)-1,3-bis(methoxymethyl)uracil (5) was prepared from the known aldehyde 3 by hydrazone formation and oxidation. Thermolysis of 5 and deprotection gave the pyrazolo[4,3-d]pyrimidine-5,7-diones 7a and 7b. Rh 2 (OAc) 4 catalyzed the transformation of 5 into to a 2 : 1 (Z)/ (E) mixture of 1,2-diuracilylethenes 9 (67%). Heating (Z)-9 in 12n HCl at 958 led to electrocyclisation, oxidation, and deprotection to afford 73% of the pyrimido[5,4-f]quinazolinetetraone 12. The Rh 2 (OAc) 4 -catalyzed reaction of 5 with 3,4-dihydro-2H-pyran and 2,3-dihydrofuran gave endo/exomixtures of the 2-oxabicyclo[4.1.0]heptane 13 (78%) and the 2-oxabicyclo[3.1.0]hexane 15 (86%), Their treatment with AlCl 3 or Me 2 AlCl promoted a vinylcyclopropane -cyclopentene rearrangement, leading to the pyrano-and furanocyclopenta[1,2-d]pyrimidinediones 14 (88%) and 16 (51%), respectively. Similarly, the addition product of 5 to 2-methoxypropene was transformed into the 5-methylcyclopentapyrimidinedione 18 (55%). The Rh 2 (OAc) 4 -catalyzed reaction of 5 with thiophene gave the exoconfigured 2-thiabicyclo[3.1.0]hexane 19 (69%). The analoguous reaction with furan led to 8-oxabicyclo[3.2.1]oct-2-ene 20 (73%), and the reaction with (E)-2-styrylfuran yielded a diastereoisomeric mixture of hepta-1,4,6-trien-3-ones 21 (75%) that was transformed into the (1E,4E,6E)-configured hepta-1,4,6-trien-3-one 21 (60%) at ambient temperature.

Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains

“…As the literature precedents attest [ 40 , 41 , 42 , 43 , 44 ] there are only a few reports on the MOM protection of nitrogen in a pyrimidine ring, and no report of N -MOM derivatives with C-6 isobutyl side-chains. Generally, N- methoxymethylation is accomplished by the substitution of MOMCl with activated O -persilylated or N -anionic uracil derivatives.…”

Advances in the Synthesis of 5- and 6-Substituted Uracil Derivatives

“…The use of furan gave 163 in 73% yield without the need of Al(III) catalysis. The acid-catalyzed intramolecular cyclization of 86 prepared from 29 (see Scheme 35),gave fused-diuracil 164 in 73% yield (Scheme 72) 20.…”