Reaction Steps
To a cold (0° C.) solution of 4-(3,3″-Dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-isophthalic acid dimethyl ester (0.710 g, 1.50 mmol) in THF (15 mL) and MeOH (15 mL) was added LiBH4 (720 mg, 33.1 mmol) and the mixture was allowed to warm to room temperature overnight. The mixture was diluted with 1.0 N NaOH (15 mL) and extracted with CH2Cl2 (5×40 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—CH3OH—NH4OH) provided 31 mg (4%) of 4-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-isophthalic acid dimethyl ester as a white foam, 155 mg (23%) of 4-3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-3-hydroxymethyl-benzoic acid methyl ester as a white foam, and 375 mg (56%) of COMPOUND 53 as a white foam. Characterization data for COMPOUND 53: 1H NMR (CDCl3) δ 1.52-1.74 (m, 3H), 2.05-2.10 (m, 1H), 2.31-2.45 (m, 8H), 2.62 (br s, 1H, OH), 3.80 (s, 3H), 3.96 (s, 2H), 4.14 (d, 2H, J=11.1 Hz), 4.46 (d, 2H, J=3 Hz), 6.82-6.87 (dd, 2H, J=4.8, 7.5 Hz), 7.10-7.17 (m, 3H), 7.25 (s, 1H), 7.62 (d, 1H, J=7.5 Hz), 8.24 (d, 2H, J=4.8 Hz); 13C NMR (CDCl3) δ 19.38, 25.62, 28.97, 50.63, 52.01, 64.91, 67.26, 122.05, 127.58, 128.07, 129.26, 131.61, 132.08, 137.64, 138.09, 143.24, 146.85, 159.86, 167.97; ES-MS m/z 446 (M+H). Anal. Calcd. For C27H31N3O3.1.3H2O: C, 69.15; H, 7.22; N, 8.96. Found: C, 69.22; H, 6.90; N, 8.87.
