반응 #1494461

반응 방정식

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

morpholine

Xantphos

NaOtBu

→

title compound

수율 66.2%

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

수율 66.2%

용매

water

1,4-dioxane

반응 조건

후처리

1. 1
   온도After cooling to room temperature
2. 2
   추출extracted with AcOEt
3. 3
   세척The extract was washed with brine
4. 4
   건조dried over MgSO4
5. 5
   농축concentrated under reduced pressure
6. 6
   기타The residue was purified by basic silica gel column chromatography
7. 7
   세척eluting with AcOEt
8. 8
   기타recrystallized from MeOH/H2O

실험 절차

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.

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