4-benzylmorpholine-2,6-dione

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (2.51 g, 9.3 mmol; prepared in a manner similar to that described in Example 23), 4-benzylmorpholin-2,6-dione (2.3 g, 11.2 mmol) and toluene (15 ml) was heated under reflux for 20 hours, then the solvent was removed in vacuo. The residue was dissolved in dimethylacetamide (15 ml) and O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (3 g, 9.3 mmol) and diisopropylethylamine (1.63 ml, 9.3 mmol) were added sequentially. The mixture was stirred at ambient temperature for 2 hours, then it was added dropwise to stirred, ice-cold water (300 ml). The resulting solid was collected by filtration and dried in vacuo to give 4-benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione (4.01 g) as an off-white solid, 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 3.6 (s, 4H) (2×ring CH2) 3.75 (s, 2H) (NCH2Ph), 4.35 (s, 2H) (ArCH2—), 7.17–7.5 (m, 8H) (8×ArH), 7.75–8.0 (m, 3H) (3×ArH), 8.25 (d, 1H) (ArH), 12.6 (s, 1H) (CONH); m/z (M+H)+ 457, 100% purity. prepared in a manner similar to was heated under reflux for 20 hours the solvent was removed in vacuo The residue was dissolved in dimethylacetamide (15 ml) it was added dropwise to stirred The resulting solid was collected by filtration dried in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (2.51 g, 9.3 mmol; prepared in a manner similar to that described in Example 23), 4-benzylmorpholin-2,6-dione (2.3 g, 11.2 mmol) and toluene (15 ml) was heated under reflux for 20 hours, then the solvent was removed in vacuo. The residue was dissolved in dimethylacetamide (15 ml) and O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (3 g, 9.3 mmol) and diisopropylethylamine (1.63 ml, 9.3 mmol) were added sequentially. The mixture was stirred at ambient temperature for 2 hours, then it was added dropwise to stirred, ice-cold water (300 ml). The resulting solid was collected by filtration and dried in vacuo to give 4-benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione (4.01 g) as an off-white solid, 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 3.6 (s, 4H) (2×ring CH2) 3.75 (s, 2H) (NCH2Ph), 4.35 (s, 2H) (ArCH2—), 7.17–7.5 (m, 8H) (8×ArH), 7.75–8.0 (m, 3H) (3×ArH), 8.25 (d, 1H) (ArH), 12.6 (s, 1H) (CONH); m/z (M+H)+ 457, 100% purity. prepared in a manner similar to was heated under reflux for 20 hours the solvent was removed in vacuo The residue was dissolved in dimethylacetamide (15 ml) it was added dropwise to stirred The resulting solid was collected by filtration dried in vacuo