Reaction #9034

Reaction equation

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

N,N-diisopropylethylamine

Allyl bromide

→

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

Solvents

CH2Cl2

CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   Washwashed consecutively with H2O (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
5. 5
   OtherPurification by column chromatography on silica gel (200:1:1 followed by 100:1:1—EtOAc:MeOH:NH4OH)
6. 6
   Otherafforded AMD9725 (36 mg, 21%) as a light yellow foam

Procedure

To a solution of N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (200 mg, 0.39 mmol) in CH2Cl2 (˜0.4 mL) was added N,N-diisopropylethylamine (90 μL, 0.52 mmol). Allyl bromide (35 μL, 0.40 mmol) was dissolved in CH2Cl2 (˜9.6 mL) and added to the amine mixture at a rate of 5.5 mL/hour. The resultant mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with CH2Cl2 (50 mL) and washed consecutively with H2O (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. Purification by column chromatography on silica gel (200:1:1 followed by 100:1:1—EtOAc:MeOH:NH4OH) followed by radial chromatography on silica gel (250:1:1—EtOAc:MeOH:NH4OH) afforded AMD9725 (36 mg, 21%) as a light yellow foam. 1H NMR (CDCl3) δ 1.56–1.75 (m, 1H), 1.97–2.08 (m, 2H), 2.24–2.31 (m, 1H), 2.65–2.77 (m, 1H), 2.77–2.91 (m, 1H), 3.21 (d, 2H, J=5.7 Hz), 3.69 (s, 2H), 3.73 (s, 2H), 3.97 (d, 1H, J=16.8 Hz), 4.04–4.16 (m, 1H), 4.17 (d, 1H, J=16.8 Hz), 5.07 (d, 1H, J=9.9 Hz), 5.15 (dd, 1H, J=17.1, 1.2 Hz), 5.88 (ddt, 1H, J=17.1, 10.5, 6.0 Hz), 7.10–7.19 (m, 5H), 7.35 (d, 2H, J=7.8 Hz), 7.42 (d, 1H, J=7.5 Hz), 7.45–7.57 (m, 1H), 7.58–7.68 (m, 1H), 8.69 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ 20.83, 22.89, 28.67, 47.95, 51.11, 52.33, 53.17, 59.68, 110.37, 115.39, 118.11, 120.91, 121.66, 127.59, 128.07, 134.13, 136.17, 136.60, 137.48, 138.56, 146.38, 155.80, 156.94. ES-MS m/z 438.3 (M+H). Anal. Calcd. for C28H31N5.0.8H2O: C, 74.40; H, 7.27; N, 15.49. Found: C, 74.36; H, 7.25; N, 15.31.

Source