Reaction Steps
To a cold (0° C.) solution of 5-cyano-2-(3,3″-dichloro-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-benzoic acid methyl ester (391 mg, 0.813 mmol) in THF (4 mL) and MeOH (4 mL) was added LiBH4 (88 mg, 4.1 mmol), and the mixture was warmed to room temperature and stirred for 3.5 h. The mixture was diluted with 1.0 N NaOH (20 mL) and extracted with CH2Cl2 (4×10 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to provide 4-(3,3″-Dichloro-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-3-hydroxymethyl-benzonitrile (367 mg) without any further purification. To a solution of the crude material (160 mg) in MeOH (4.5 mL) was added H2O (2.5 mL) and NaBO3.4H2O (108 mg, 0.707 mmol). The resultant mixture was heated to 50° C. for 5 h and stirred at room temperature overnight. The reaction mixture was concentrated and the residue was purified by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 90:5:5 then 85:10:5) to afford COMPOUND 52 (54 mg, 32% over 2 steps) as a white solid. 1H NMR (CDCl3) δ 1.63-1.79 (m, 3H), 1.93-2.06 (m, 1H), 2.11-2.30 (m, 2H), 2.33-2.47 (m, 2H), 3.63 (s, 2H), 4.59 (d, 2H, J=9.92 Hz), 4.41 (s, 2H), 4.99 (br s, 1H), 5.67 (br s, 1H), 6.15 (br s, 1H), 6.85-6.96 (m, 2H), 7.04 (d, 1H, J=7.8 Hz), 7.24 (d, 1H, J=1.8 Hz), 7.38 (d, 1H, J=1.5 Hz), 7.48 (dd, 2H, J=7.8, 1.5 Hz), 8.30 (dd, 2H, J=4.5, 1.2 Hz); 13C NMR (CDCl3) δ 24.98, 31.59, 57.28, 62.72, 66.56, 123.45, 126.39, 128.11, 129.90, 131.55, 131.70, 137.47, 140.08, 142.64, 147.77, 158.55, 169.17; ES-MS m/z 473 (M+1+H). Anal. Calcd. for C24H24N4Cl2O2.0.5H2O: C, 60.01; H, 5.25; N, 11.66. Found: C, 60.00; H, 5.15; N, 11.49.
