Diisopropylethylamine → 4-(4-fluoro-3-(4-(2-oxo-2-(piperidin-1-yl)ethoxy)piperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (0.20 g, 0.67 mmol) and HBTU (0.381 g, 1.01 mmol) were added to DMA (4 mL), to this was added N-ethyl-N-isopropylpropan-2-amine (0.179 mL, 1.01 mmol) and then 1-(piperidin-1-yl)-2-(piperidin-4-yloxy)ethanone (112) (0.152 g, 0.67 mmol). The reaction was stirred for 2 hours before being evaporated to dryness and 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 material (0.303 g, 89% yield); 1H NMR (400.132 MHz, DMSO) δ 1.07-1.39 (8H, m), 1.46-1.56 (1H, m), 1.61-1.71 (1H, m), 2.76-2.85 (1H, m), 3.02-3.09 (2H, m), 3.10-3.20 (4H, m), 3.34-3.41 (1H, m), 3.66-3.75 (1H, m), 3.90-3.93 (2H, m), 4.08-4.12 (2H, m), 6.99 (1H, t), 7.09-7.21 (2H, m), 7.57-7.69 (1H, m), 7.72-7.76 (1H, m), 8.02-8.06 (2H, m), 12.34 (1H, s); m/z (LC-MS, ESI+), RT=1.76 (M+H 507.5).

1. custombefore being evaporated to dryness
2. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
3. additionFractions containing the desired compound
4. customwere evaporated to dryness

ORD-Eintrag

ord-0456e4aa719846bc97de1ce91e9d731b

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08129380B2