Dimethylformamide → HCID 19787904, compound

Participants

Reaction Steps

To a slurry of 2-[5-amino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (0.414 g) in dry tetrahydrofuran (3 mL) and dichloromethane (5 mL) was added isopropyl isocyanate (110 uL). After overnight stiring, dimethylformamide (1.5 mL), triethylamine (100 uL) and isopropyl isocyanate (50 uL) were added. The reaction mixture was heated to reflux for 24 h. The mixture was cooled to room temperature and cuprous chloride (120 mg) followed by three portions of isopropyl isocyanate (50 uL, 50 uL, and 25 uL) were added. The reaction mixture was diluted with diethyl ether and rinsed with dilute hydrochloric acid and brine. The organic phase was dried and evaporated to afford an oil which was purified by chromatography, with chloroform:methanol (gradient 100:0, 97:3) as the eluent. This afforded 160 mg of a yellow-green solid. Analysis by NMR showed line broadening, indicative of contamination by a heavy metal. The remaining 135 mg sample was dissolved in methyl tert-butyl ether and rinsed with 5% disodium EDTA solution followed by dilute aqueous ammonia. The organic phase was dried and evaporated to afford the title compound (120 mg) as an off-white powder; TLC: Rf =0.46, chloroform:methanol (9:1); NMR: 8.62 (s,1), 7.52 (dd,2), 7.26 (dd,2), 4.6 (dd,2), 4.04 (d,1), 2.25 (m,1), 1.09 (d,6), 0.85 (d,3), 0.76 (d,3); MS: m/z=500(M+1).

Provenance & Evidence