Reaction Steps
To a stirred solution of sodium (320 mg, 14 mmol) in anhydrous MeOH (15 mL) was added NH2OH.H2O (550 mg, 7.9 mmol) followed by a solution 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 (700 mg, 1.6 mmol) in anhydrous MeOH (7 mL). The mixture was stirred for 2 h, at which time TLC indicated that the reaction had stalled. A solution of sodium (320 mg, 14 mmol) and NH2OH.H2O (550 mg, 7.9 mmol) in anhydrous MeOH (8 mL) was added to the reaction mixture and stirring was continued for 2 hours. The reaction mixture was diluted with CHCl3 (100 mL) and poured into a saturated NaHCO3 solution (100 mL). The aqueous layer was extracted with CHCl3 (5×100 mL). The combined organic portions were concentrated to 100 mL, washed once with saturated NaHCO3 solution (20 mL), dried over Na2SO4, concentrated, and dried under high vacuum to give COMPOUND 45 (647 mg, 92%) as an off-white solid. 1H NMR (DMSO-d6) δ 1.46 (d, 2H, J=12.0 Hz), 1.69-1.84 (m, 1H), 2.01-2.11 (m, 1H), 2.48 (s, 6H), 3.59 (s, 2H), 4.13 (d, 2H, J=3.8 Hz), 4.40 (d, 2H, J=10.8 Hz), 4.79-4.85 (m, 1H), 5.74 (s, 1H), 6.84-6.91 (m, 3H), 7.06 (d, 1H, J=7.5 Hz), 7.18-7.28 (m, 3H), 8.14 (d, 2H, J=3.3 Hz), 8.75 (s br, 1H), 10.82 (s br, 1H); 13C NMR (D2O) δ 18.38(2), 24.40, 25.32(2), 55.27, 60.85(2), 64.75, 122.31(2), 123.64, 124.88, 126.82, 132.62, 137.64(2), 138.08, 143.18, 145.86(2), 158.58, 164.49; ES-MS m/z 447 (M+H). Anal. Calcd. For C26H30N4O3.1.1H2O: C, 66.96; H, 6.96; N, 12.01. Found: C, 66.95; H, 6.71; N, 11.66.
