Réaction #1494461

Équation de réaction

1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

morpholine

Xantphos

NaOtBu

→

title compound

Rendement 66.2%

1-(2-Fluoro-4-morpholin-4-ylphenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Rendement 66.2%

Solvants

water

1,4-dioxane

Conditions de réaction

Traitement

1. 1
   TempératureAfter cooling to room temperature
2. 2
   Extractionextracted with AcOEt
3. 3
   LavageThe extract was washed with brine
4. 4
   Séchagedried over MgSO4
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   AutreThe residue was purified by basic silica gel column chromatography
7. 7
   Lavageeluting with AcOEt
8. 8
   Autrerecrystallized from MeOH/H2O

Mode opératoire

A suspension of 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (244 mg, 0.5 mmol), morpholine (0.053 mL, 0.6 mmol), Pd2(dba)3 (18.3 mg, 0.02 mmol), Xantphos (46.3 mg, 0.08 mmol), and NaOtBu (67.3 mg, 0.7 mmol) in 1,4-dioxane (2.5 mL) was stirred for 2 h at 90° C. under Ar atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with AcOEt and recrystallized from MeOH/H2O to give the title compound (148 mg, 66% yield) as off-white crystals: mp 226-228° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.16-3.19 (4H, m), 3.83-3.87 (4H, m), 3.89 (3H, s), 6.31 (1H, t, J=9.0 Hz), 6.45 (1H, dd, J=2.6, 9.0 Hz), 6.58 (1H, dd, J=2.6, 14.7 Hz), 7.26 (1H, d, J=1.9 Hz), 7.33-7.45 (5H, m), 7.74 (1H, d, J=2.3 Hz), 7.77 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 448 [M+H]+. Anal. Calcd for C24H22FN5O3: C, 64.42; H, 4.96; N, 15.65. Found: C, 64.33; H, 4.98; N, 15.59.

Source