Reaction #9033

Reaction equation

Allyl bromide

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

N,N-diisopropylethylamine

→

foam

Yield 56.6%

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

Yield 56.6%

Solvents

CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   Washwashed consecutively with H2O (2×5 mL), saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL)
2. 2
   ExtractionThe aqueous layer was extracted with CH2Cl2 (20 mL)
3. 3
   Dryingthe combined organic extracts were dried (MgSO4)
4. 4
   Concentrationconcentrated under reduced pressure

Procedure

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.

Source