Triethylamine → Benzyl hydrogen 2-((3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamido)methyl)-5-fluorophenylphosphonate

Participants

Reaction Conditions

Reaction Steps

A solution of N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.200 g, 0.35 mmol) in dimethyl sulfoxide (5 ml) was flushed with argon and then treated triethylamine (0.25 ml, 1.8 mmol), tetrakis(triphenylphosphine)palladium(0) (0.10 g) and dibenzyl phosphite (0.25 ml, 1.06 mmol). The reaction mixture was then sealed and heated at 80° C. for 16 h. The reaction mixture was then diluted with ethyl acetate, washed with 0.1 N hydrochloric acid, brine, dried over anhydrous magnesium sulfate and concentrated. Purification of the residue by preparative HPLC (column YMC Pack C-18, 5μ, 20×250 mm, elution gradient acetonitrile-water 0.1% trifluoroacetic acid) gave 0.150 g (60% yield) of the title material as a white solid; mp 142° C. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.58 (6H, s, 2×CH3), 4.0 (4H, m, 2×CH2), 4.73 (2H, broad s, OCH2), 5.05 (2H, d, J=8.6 Hz, NCH2), 5.28 (2H, s, OCH2), 7.20 (1H, m, aromatic), 7.29-7.34 (6H, m, aromatics), 7.45-7.64 (6H, m, aromatics), 8.24 (1H, broad, NH). MS (ESI+) m/z 608 [M+H+].

Provenance & Evidence