4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-nitrophthalazin-1(2H)-one → 8-amino-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-5-nitrophthalazin-1 (2H)-one (34b) with 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)-8-nitrophthalazin-1 (2H)-one (34a) (6 mg, 6.81 μmol) in ethanol (2 ml) was added to 5% palladium on carbon (2 mg, 0.94 μmol) in ethanol (5 mL) at 20° C. and the resulting mixture stirred at 20° C. for 5 hours, under an atmosphere of hydrogen. The catalyst was filtered and washed with ethanol and the solvent evaporated to a foam. Further ethanol and 5% palladium on charcoal (10 mg) were added and mixture stirred for a further 5 hours, under an atmosphere of hydrogen. The catalyst was filtered and washed with ethanol. Evaporation gave a gum, which was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired compound as a colourless gum (1.700 mg, 60.8%); 1H NMR (400.132 MHz, CDCl3) δ 1.25-1.31 (1H, m), 1.51-1.82 (2H, m), 1.89-1.98 (1H, m), 3.09-3.17 (1H, m), 3.38 (3H, s), 3.46-3.51 (2H, m), 3.55-3.63 (1H, m), 3.98-4.05 (1H, m), 4.16 (2H, s), 6.43 (2H, s), 6.79 (1H, d), 6.85 (1H, d), 7.00-7.04 (1H, m), 7.25-7.31 (2H, m), 7.41-7.45 (1H, m), 9.56 (1H, s); m/z (LC-MS, ESI+), RT=1.71 (M+H 411.5).

Provenance & Evidence