Reaction Steps
To a cold (0° C.) mixture of LiAlH4 (187 mg, 4.93 mmol) in dry THF (5 mL) was added 5-cyano-2-{[(3-methyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzoic acid methyl ester (245 mg, 0.57 mmol) as a solution in THF (6 mL). The resultant mixture was stirred at room temperature for 5 hours then cooled in an ice water bath. The mixture was treated with saturated aqueous sodium-potassium tartrate (11 mL) and diluted with THF (11 mL). The phases were separated and the aqueous phase was extracted with THF (2×11 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) followed by radial chromatography on silica gel (1 mm plate, 75:1:1 CH2Cl2-MeOH—NH4OH) gave COMPOUND 405 (85 mg, 34%) as a white solid. 1H NMR (CDCl3) δ 1.46-1.64 (m, 4H), 1.91-1.98 (m, 1H), 2.06-2.19 (m, 5H), 2.51-2.59 (m, 1H), 2.68-2.77 (m, 1H), 3.62 (d, 2H, J=12.3 Hz), 3.72-3.76 (m, 3H), 3.84 (dd, 1H, J=7.5, 7.8 Hz), 4.06-4.15 (m, 2H), 4.30 (d, 1H, J=11.4 Hz), 6.92-7.07 (m, 3H), 7.15-7.29 (m, 3H), 7.35 (d, 1H, J=7.5 Hz), 8.27-8.31 (m, 2H); 13C NMR (CDCl3) δ 17.32, 19.78, 20.72, 28.66, 45.11, 53.06, 53.62, 56.48, 61.63, 120.59, 121.46, 124.93, 129.32, 130.07, 133.01, 133.58, 134.44, 135.60, 137.18, 141.23, 142.21, 144.76, 145.58, 155.32, 155.89; ES-MS m/z 403 (M+H). Anal. Calcd. for C25H30N4O.1.0CH3OH: C, 71.86; H, 7.89; N, 12.89. Found: C, 71.78; H, 7.59; N, 12.59.
