Reaction Steps
To a cold (0° C.) mixture of LiAlH4 (226 mg, 5.94 mmol) in dry THF (6 mL) was added 5-cyano-2-{[(3-isopropyl-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-benzoic acid methyl ester (0.253 g, 0.59 mmol) as a solution in THF (5 mL). The resultant mixture was stirred at room temperature for 4 hours then cooled in an ice water bath. The mixture was treated with saturated aqueous sodium-potassium tartrate (5 mL) and diluted with THF (10 mL). The phases were separated and the aqueous phase was extracted with THF (2×10 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, 50:1:1 CH2Cl2-MeOH—NH4OH) gave COMPOUND 386 (42 mg, 17%) as a white solid. 1H NMR (CDCl3) δ 1.04 (d, 6H, J=6.0 Hz), 2.10 (s, 3H), 2.97 (septet, 1H), 3.73 (s, 2H), 3.76 (s, 2H), 3.82 (s, 2H), 3.90 (s, 2H), 4.24 (s, 2H), 6.38 (br s, 1H), 7.05-7.17 (m, 3H), 7.20-7.28 (m, 2H), 7.39 (d, 1H, J=7.2 Hz), 7.52 (dd, 1H, J=1.5, 7.8 Hz), 8.35-8.38 (m, 2H); 13C NMR (CDCl3) δ 18.53, 23.46 (2 carbons), 27.99, 46.54, 56.73, 58.03, 59.15, 63.42, 122.81, 123.13, 126.37, 130.24, 132.05, 133.62, 135.75, 138.55, 142.41, 143.66, 143.76, 146.32, 146.51, 155.10, 156.35; ES-MS m/z 405 (M+H). Anal. Calcd. for C25H32N4O.0.9H2O: C, 71.36; H, 8.10; N, 13.32. Found: C, 71.58; H, 7.93; N, 12.95.
