Reaction Steps
To a solution of 4-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile (0.5371 g, 1.2 mmol) in THF (12 mL) at 0° C. was added LiBH4 (0.2086 g, 9.6 mmol), then heated to 70° C. and stirred for 18 hours. 1N NaOH (25 mL) and CH2Cl2 (50 mL) were added and stirred for 10 minutes. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by column chromatography on silica gel (75:1:1 CH2Cl2-MeOH—NH4OH) provided 0.2330 g (48%) of COMPOUND 402 as a white solid. 1H NMR (CDCl3) δ 1.61 (s, 5H), 2.07 (s, 6H), 3.69 (s, 2H), 3.73 (s, 2H), 3.91 (s, 2H), 4.55 (s, 2H), 6.69-6.78 (bs, 1H), 6.94-6.97 (m, 1H), 7.02-7.08 (m, 3H), 7.21 (d, 1H, J=1.5 Hz), 7.49-7.55 (m, 1H), 7.77 (d, 1H, J=8.1 Hz), 8.05 (d, 1H, J=2.1 Hz), 8.45-8.48 (m, 1H). 13C NMR (CDCl3) δ 18.71, 24.43, 46.39, 51.43, 53.95, 63.49, 64.78, 122.10, 123.09, 126.25, 129.32, 130.26, 131.30, 132.25, 136.21, 137.16, 137.26, 141.33, 143.29, 144.59, 147.94, 156.80, 165.90. ES-MS m/z 425.4 (M+H). Anal. Calcd. for C24H29N4ClO.0.3H2O: C, 66.98; H, 6.93; N, 13.02; Cl, 8.24. Found: C, 67.11; H, 6.54; N, 12.13; Cl, 8.99.
