Reaction Steps
Using General Procedure F: A solution of 4,6-dimethyl-pyrimidine-5-carboxylic acid from above (prepared as described in patent application PCT/US00/11632) (42 mg, 0.28 mmol), (3-aminomethyl-benzyl)-(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (100 mg, 0.25 mmol), HOBT (38 mg, 0.28 mmol) and 4-methylmorpholine (40 μL, 0.38 mmol) in DMF (0.8 mL) was flushed with N2. EDCI (54 mg, 0.28 mmol) was added and the mixture was stirred at room temperature overnight. Purification of the colorless syrup (150 mg) by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:2:1) followed by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:2:1) afforded AMD11084 (80 mg, 60%) as a white foam. 1H NMR (CDCl3) δ 1.64-1.77 (m, 1H), 1.91-2.08 (m, 2H), 2.18-2.34 (m, 1H), 2.37 (s, 6H), 2.69-2.91 (m, 2H), 3.73 (s, 2H), 3.80 (d, 1H, J=16.5 Hz), 4.00 (d, 1H, J=16.5 Hz), 4.07-4.13 (m, 1H), 4.69 (d, 2H, J=5.7 Hz), 6.53 (t, 1H, J=5.7 Hz), 6.96-7.10 (m, 3H), 7.16-7.22 (m, 2H), 7.29-7.31 (m, 2H), 7.40-7.45 (m, 3H), 8.64 (d, 1H, J=3.6 Hz), 8.81 (s, 1H); 13C NMR (CDCl3) δ 21.71, 22.28, 24.38, 29.55, 44.29, 49.22, 55.11, 61.90, 111.12, 118.82, 121.68, 122.78, 127.32, 128.67, 129.09, 129.24, 130.48, 135.22, 137.66, 137.83, 140.30, 147.22, 156.42, 157.60,157.91, 163.43, 166.96. ES-MS m/z 532.4 (M+H). Anal. Calcd. for C32H33N7O.0.4CH2Cl2: C, 68.80; H, 6.02; N, 17.33. Found: C, 68.56; H, 6.09; N, 17.34.
