反応 #167601

反応方程式

3,6-dichloropyridazine

1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride

sodium tert-butoxide

→

title compound

4-(6-chloropyridazin-3-yl)-1,4-diazatricyclo[4.3.1.13,8]undecane

溶媒

toluene

反応条件

後処理

1. 1
   その他The mixture was purged with nitrogen
2. 2
   温度After cooling to room temperature
3. 3
   その他the reaction was quenched
4. 4
   workup.ADDITIONby pouring into a 5% aqueous NaHCO3 solution
5. 5
   抽出The mixture was extracted with chloroform (3×)
6. 6
   洗浄washed with brine
7. 7
   乾燥dried (MgSO4)
8. 8
   ろ過filtered
9. 9
   濃縮concentrated
10. 10
    その他The crude product was purified by preparative HPLC [Waters 30×100 mm XBridge Prep C18, 5 μm, 40 mL/min, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

実験手順

A solution of the product of Example 2 (0.30 g, 2.0 mmol) in dry toluene (10 mL) was treated with 3,6-dichloropyridazine (0.71 g, 4.8 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3; 0.037 g, 0.04 mmol; Alfa Aesar), 1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride (0.057 g, 0.12 mmol; Strem), and sodium tert-butoxide (0.45 g, 4.0 mmol; Aldrich). The mixture was purged with nitrogen and heated to 90° C. for 8 hours. After cooling to room temperature, the reaction was quenched by pouring into a 5% aqueous NaHCO3 solution. The mixture was extracted with chloroform (3×), washed with brine, dried (MgSO4), filtered and concentrated. The crude product was purified by preparative HPLC [Waters 30×100 mm XBridge Prep C18, 5 μm, 40 mL/min, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: MS (DCI/NH3) m/z 265 (M+H)+.

出典