반응 #489061

반응 방정식

4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine

3-morpholin-4-yl-propan-1-ol

sodium hydride

→

4-{3-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxy]-propyl}-morpholine

수율 76.1%

용매

THF

반응 조건

후처리

1. 1
   기타to come to room temperature
2. 2
   workup.ADDITIONAfter completion of addition
3. 3
   농축The reaction was concentrated onto SiO2
4. 4
   기타purified via flash chromatography

실험 절차

To a stirred solution of 3-morpholin-4-yl-propan-1-ol (1.0 mmol, 0.145 g) in THF (3 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil) (1.3 mmol, 0.052 g) and continued stirring for 15 min. The reaction mixture was allowed to come to room temperature. To the mixture was added 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (Example 1, 0.74 mmol, 0.26 g). After completion of addition, the reaction mixture was warmed to 70° C. for 3 h. The reaction was concentrated onto SiO2 and purified via flash chromatography using 20-50% ethyl acetate in hexanes to give 4-{3-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxy]-propyl}-morpholine (0.26 g, 75%). The free amine may be dissolved in DCM and 2 N HCl in diethyl ether followed by evaporation of the solvents to provide the title compound. LCMS: m/z 463 [M+1]. 1H NMR (400 MHz, CDCl3): δ 7.32-7.49 (5H, m), 7.21-7.26 (2H, m), 7.03-7.09 (2H, m), 6.74 (1H, s), 5.12 (2H, s), 4.58 (2H, t), 3.67-3.76 (4H, m), 2.83-2.91 (2H, m), 2.41-2.56 (6H, m), 1.98-2.08 (2H, m), 1.56-1.68 (2H, m), 1.21-1.33 (2H, m), 0.83 (3H, t).

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