2-(Tert-butoxycarbonylmethyl-amino)-propionic acid methyl ester → {3-[2-Fluoro-5-(4-oxo-3,4-dihydro-phthalazin-1-ylmethyl)-phenyl]-5-methyl-2,4-dioxo-imidazolidin-1-yl}-acetic acid tert-butyl ester

Beteiligte Stoffe

Reaktionsschritte

To a suspension of 4-(3-isocyanato-benzyl)-2H-phthalazin-1-one (2)(3.12 mmol) in dry DCM (80 ml) in the presence of activated 4 Å molecular sieves (ca 5 g) was added 2-(tert-butoxycarbonylmethyl-amino)-propionic acid methyl ester (33A)(1.07 g, 4.7 mmol). The reaction was then stirred for 48 hours at ambient temperature. HPLC analysis showed there to a mixture of cyclised and uncyclised ureas 1:1 ratio. The mixture was filtered and concentrated in vacuo. The crude oil was then subjected to flash chromatography eluent: 1:1 hexane ethyl acetate, Rf=0.09. Single peak in LC-MS analysis, (1.3 g, 95% purity) and required no further purification; m/z (LC-MS, ESP), RT=3.66 mins (M+H) 481—compound cyclised on column

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