Reaktion #91763

Reaktionsgleichung

HCl

3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate

4-fluorophenylisocyanate

triethylamine

→

1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(4-fluoro-phenyl)-urea

Ausbeute 69.0%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe product was isolated by filtration
2. 2
   Waschenwashed with 1N aq. HCl (20 mL), acetonitrile (20 mL)
3. 3
   Sonstigedried overnight in vacuo

Vorschrift

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.50 g, 1.80 mmol) and 4-fluorophenylisocyanate (0.25 g, 1.80 mmol) in acetonitrile (20 mL), was added triethylamine (0.51 mL, 3.60 mmol) at room temperature under nitrogen. After 1 h, 1N aq. HCl (20 mL) was added and the mixture was stirred for 10 min. The product was isolated by filtration, washed with 1N aq. HCl (20 mL), acetonitrile (20 mL) and dried overnight in vacuo to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(4-fluoro-phenyl)-urea as an off-white solid (0.51 g, 68% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 2.13 min (98.98%); mp: 262-264° C.; 1H NMR (DMSO-d6) δ 1.92-2.13 (m, 1H), 2.29-2.47 (m, 1H), 2.54-2.69 (m, 1H), 2.82-3.00 (m, 1H), 4.31 (d, J=17.4 Hz, 1H), 4.37-4.55 (m, 3H), 5.11 (dd, J=13.2, 5.1 Hz, 1H), 6.73 (t, J=5.9 Hz, 1H), 7.06 (t, J=8.9 Hz, 2H), 7.37-7.48 (m, 3H), 7.52 (s, 1H), 7.70 (d, J=7.9 Hz, 1H), 8.67 (s, 1H), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.8, 47.1, 51.6, 115.1 (d, J=22.0 Hz,), 119.4 (d, J=6.6 Hz), 121.9, 122.9, 126.9, 130.3, 136.8, 142.4, 144.9, 155.3 (d, J=4.4 Hz), 158.5, 168.0, 171.0, 172.9; LCMS: MH=411; Anal Calcd for C21H19FN4O4: C, 61.46; H, 4.67; N, 13.65. Found: C, 61.44; H, 4.53; N, 13.46.

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