反応 #9033

反応方程式

Allyl bromide

N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine

N,N-diisopropylethylamine

→

foam

収率 56.6%

1H-benzimidazol-2-ylmethyl -(4-diallylaminomethyl-benzyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

収率 56.6%

溶媒

CH2Cl2

CH2Cl2

反応条件

後処理

1. 1
   洗浄washed consecutively with H2O (2×5 mL), saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL)
2. 2
   抽出The aqueous layer was extracted with CH2Cl2 (20 mL)
3. 3
   乾燥the combined organic extracts were dried (MgSO4)
4. 4
   濃縮concentrated under reduced pressure

実験手順

To a solution of N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (156 mg, 0.39 mmol) in CH2Cl2 (4 mL) was added N,N-diisopropylethylamine (65 μL, 0.37 mmol). Allyl bromide (35 μL, 0.40 mmol) was added dropwise and the resultant mixture stirred at room temperature for 3 days. The reaction mixture was diluted with CH2Cl2 (50 mL) and washed consecutively with H2O (2×5 mL), saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL). The aqueous layer was extracted with CH2Cl2 (20 mL) and the combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to afford a light yellow foam (100 mg). Purification by column chromatography on silica gel (200:1:1 followed by 100:1:1—CH2Cl2:MeOH:NH4OH) followed by radial chromatography on silica gel (1000:1:1—EtOAc:MeOH:NH4OH) afforded AMD9725 (24.5 mg, 14%) as a light yellow foam. 1H NMR (CDCl3) δ 1.62–1.75 (m, 1H), 1.97–2.08 (m, 2H), 2.22–2.30 (m, 1H), 2.66–2.77 (m, 1H), 2.77–2.92 (m, 1H), 3.01 (d, 4H, J=6.3 Hz), 3.48 (s, 2H), 3.74 (s, 2H), 3.99 (d, 1H, J=16.8 Hz), 4.07–4.12 (m, 1H), 4.18 (d, 1H, J=16.8 Hz), 5.09–5.17 (m, 4H), 5.83 (ddt, 2H, J=16.8, 10.2, 6.3 Hz), 7.15–7.20 (m, 5H), 7.34 (d, 2H, J=7.8 Hz), 7.41 (d, 1H, J=7.8 Hz), 7.48–7.56 (m, 1H), 7.60–7.69 (m, 1H), 8.69 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ 19.69, 21.65, 27.53, 46.90, 52.08, 54.63, 55.44, 58.47, 109.24, 115.61, 117.04, 119.79, 120.49, 126.67, 127.13, 132.99, 134.17, 135.45, 136.13, 136.56, 145.22, 154.64, 155.80. ES-MS m/z 478.4 (M+H). Anal. Calcd. for C31H35N5.0.5H2O: C, 76.51; H, 7.46; N, 14.39. Found: C, 76.67; H, 7.45; N, 14.18.

出典