5-Fluoro-1-(2-propyn-1-yl)-2,4(1H,3H)-pyrimidinedione synthesis

Yield:69849-33-8 63%

Reaction Conditions:

with 1,8-diazabicyclo[5.4.0]undec-7-ene in acetonitrile; for 1.5 h;Inert atmosphere;Reflux;

Steps:

4.1.5. Synthesis of 5-fluoro-1-(prop-2-yn-1-yl)pyrimidine-2,4(1H,3H)-dione 7

Propargyl bromide (1.0 eq) was added dropwise to a solution of5-fluorouracil 1 (0.5 g, 1.0 eq) and DBU (1.0 eq) in dry CH3CN (7 ml)at 0 C under a nitrogen atmosphere. The reaction mixture wasrefluxed for 1.5h, then quenched with HCl(aq) 1M (15 ml) andextracted with EtOAc (25 ml). The organic layer was dried overNa2SO4, filtered-off and concentrated under vacuo to give a residuethat was purified by silica gel coloumn chromatography elutingwith 40% EtOAc in n-hexane to afford the title compound 7 as whitesolid. 63% yield; m.p. 140e142 C; silica gel TLC Rf 0.20 (EtOAc/nhexane40% v/v); dH (400 MHz, DMSO-d6): 11.92 (s, 1H, exchangewith D2O, CONHCO), 8.17 (d, J 6.6 Hz, 1H, AreH), 4.49 (d,J 2.3 Hz, 2H, CH2), 3.48 (t, J 2.3 Hz, 1H, CH); dC (100 MHz,DMSO-d6): 158.40 (d, J2 CF 25.9 Hz), 150.12, 140.87 (d, J2CF 230.5 Hz), 129.96 (d, J2 CF 33.9 Hz), 79.18, 77.18, 38.05; dF(376 MHz, DMSO-d6): 168.41; m/z (ESI negative) calcd forC7H4FN2O2 [M H]- 167.0, found 167.1.

References:

ALOthman, Zeid A.;Bonardi, Alessandro;El-Haggar, Radwan;Eldehna, Wagdy M.;Lomelino, Carrie;McKenna, Robert;Nocentini, Alessio;Osman, Sameh M.;Petreni, Andrea;Supuran, Claudiu T. [European Journal of Medicinal Chemistry,2020,vol. 190]