反应详情

Using General Procedure B, reaction of (R)-2-[4-(1-pyridin-2-yl-ethylamino)-butyl]-isoindole-1,3-dion and 3-methyl-pyridine-2-carbaldehyde in CH2Cl2 with NaBH(OAc)3 gave 2-{4-[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-butyl}-isoindole-1,3-dione. 1H NMR (CDCl3) δ 1.21-1.32 (m, 2H), 1.38-1.47 (m, 5H), 2.25 (s, 3H), 2.35-2.54 (m, 1H), 2.54-2.60 (m, 1H), 3.48 (t, 2H, J=7.5 Hz), 3.79 (s, 2H), 3.94-4.00 (m, 1H), 6.97-6.99 (m, 1H), 7.05-7.10 (m, 1H), 7.29-7.36 (m, 2H), 7.56-7.57 (m, 1H), 7.66-7.69 (m, 2H), 7.78-7.81 (m, 2H), 8.27 (d, 1H, J=3.5 Hz), 8.49 (d, 1H, J=3.5 Hz). Deprotection with H2NNH2.H2O following General Procedure E gave N1-(3-methyl-pyridin-2-ylmethyl)-N1-(1-pyridin-2-yl-ethyl)-butane-1,4-diamine as a beige oil. 1H NMR (CDCl3) δ 1.03 (s, 1H), 1.20-1.26 (m, 2H), 1.31-1.37 (m, 2H), 1.49 (d, 3H, J=6.0 Hz), 2.31 (s, 3H), 2.39-2.56 (m, 4H), 3.83 (s, 2H), 3.97-4.04 (m, 1H), 7.07-7.09 (m, 2H), 7.39 (d, 2H, J=9.0 Hz), 7.61-7.62 (m, 1H), 8.34-8.36 (m, 1H), 8.53-8.55 (m, 1H). Conversion to the HBr salt using General Procedure D gave COMPOUND 243 as a white solid. 1H NMR (D2O) 1.47-1.49 (m, 4H), 1.59 (d, 3H, 6.6 Hz), 2.45 (s, 3H), 2.60-2.66 (m, 1H), 2.70-2.77 (m, 1H), 2.85-2.86 (m, 2H), 4.30 (s, 2H), 4.57-4.60 (m, 2H), 7.81-7.85 (m, 1H), 7.99 (t, 1H, J=6.6 Hz), 8.13 (d, 1H, J=9.0 Hz), 8.32 (d, 1H, J=7.2 Hz), 8.56-8.58 (m, 2H), 8.77 (d, 1H, J=5.1 Hz). 13C NMR (D2O) δ 15.00, 17.00, 23.97, 25.01, 39.52, 51.06, 52.70, 59.88, 125.85, 126.82, 126.88, 137.10, 138.28, 142.11, 148.19, 148.25, 152.29, 156.10. ES-MS m/z 299 (M+H). Anal. Calcd. for C18H26N4.3.4HBr.0.3C4H10O.2.3H2O: C, 36.19; H, 5.85; N, 8.79; Br, 42.64. Found: C, 36.11; H, 5.54; N, 8.75; Br, 42.65.