Reacción #489083

Ecuación de reacción

HCl

3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride

2-(2-bromoethyl)-1,3-dioxane

potassium carbonate

→

title compound

Rendimiento 73.7%

3-Butyl-4-(4-cyclohexyloxy-phenyl)-6-[1-(2-[1,3]dioxan-2-yl-ethyl)-piperidin-4-yloxy]-pyridazine dihydrochloride

Rendimiento 73.7%

Disolventes

ether

water EtOAc

DCM

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrodried
2. 2
   Otrocondensed in vacuo
3. 3
   Otrothe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
4. 4
   Otroto give a colorless sticky solid, which
5. 5
   workup.WAITkept at room temperature for 10 min
6. 6
   Otrocondensed
7. 7
   Otrotriturated with hexanes

Procedimiento

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (Example 14, 0.1 mmol, 49 mg) in DMF (1 mL) was added 2-(2-bromoethyl)-1,3-dioxane (0.3 mmol, 40 μL), and potassium carbonate (0.4 mmol, 56 mg). The mixture was stirred at room temperature for 3 hours. It was then diluted with water/EtOAc. The organic layers were combined, dried, and condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1 mL), 1N HCl in ether (1 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (22 mg). LCMS: m/z 525 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.72 and 7.81 (1H, s), 7.44-7.49 (2H, m), 7.12-7.17 (2H, m), 5.38-5.57 (1H, m), 4.76-4.79 (1H, m), 4.41-4.48 (1H, m), 4.06-4.13 (2H, m), 3.72-3.86 (3H, m), 3.55-3.60 (1H, m), 3.22-3.39 (4H, m), 3.12-3.17 (2H, m), 2.23-2.57 (3H, m), 1.98-2.17 (6H, m), 1.79-1.86 (2H, m), 1.23-1.64 (11H, m), 0.82 (3H, t).

Fuente