反应详情

Using General Procedure A: Reaction of 2-[4-(5,6,7,8-tetrahydro-quinolin-8-ylamino)-butyl)-isoindole-1,3-dione, 2-bromomethyl-6-methoxymethyl-pyridine (Gillespie, R. J. et al. PCT Int. Appl. (2002), WO 2002055083), and DIPEA in CH3CN gave 2-{4-[(6-methoxymethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butyl}-isoindole-1,3-dione as a yellow oil. Deprotection with H2NNH2.H2O following General Procedure E gave the free base. Conversion to the HBr salt using General Procedure D gave COMPOUND 356 as a white solid. 1H NMR (D2O) δ 1.52-1.70 (m, 4H), 1.75-1.89 (m, 1H), 1.98-2.10 (m, 1H), 2.16-2.22 (m, 1H), 2.39-2.43 (m, 1H), 2.59-2.68 (m, 1H), 2.84-3.02 (m, 5H), 3.53 (s, 3H), 4.28 (d, 1H, J=15.9 Hz), 4.36 (d, 1H, J=15.9 Hz), 4.49 (dd, 1H, J=5.7, 10.5 Hz), 4.88 (s, 2H), 7.80 (dd, 1H, J=5.7, 7.8 Hz), 7.91 (d, 1H, J=7.8 Hz), 8.08 (d, 1H, J=7.8 Hz), 8.26 (d, 1H, J=8.1 Hz), 8.47 (dd, 1H, J=7.8, 8.1 Hz), 8.57 (d, 1H, J=5.7 Hz); 13C NMR (D2O) δ 20.42 (2 carbons), 24.93, 25.01, 27.62, 39.53, 51.42, 53.24, 59.28, 60.01, 70.38, 125.20, 125.72, 126.27, 140.04, 140.29, 146.84, 146.93, 151.24, 153.50, 153.82; ES-MS m/z 355 (M+H). Anal. Calcd. for C21H30N4.3.4HBr.1.2H2O: C, 38.73; H, 5.54; N, 8.60; Br, 41.72. Found: C, 39.06; H, 5.54; N, 8.44; Br, 41.42.