2,3-Dihydroxybutanedioate → (5-aminomethyl-2-{[(1H-benzoimidazol-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol

Participants

Reaction Steps

To a solution of 2-{[(4-cyano-2-methoxycarbonyl-benzyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-benzoimidazole-1-carboxylic acid tert-butyl ester (0.5065 g, 1.0 mmol) in dry THF (5 mL) under Ar at 0° C. was slowly added 1.0 M LiAlH4 in THF (9.6 mL, 9.6 mmol). The reaction was stirred at room temperature for 3 hours, then cooled to 0° C. Saturated aqueous KNa Tartrate (Rochelle's salt, 30 mL) was slowly added, and the phases were separated. The aqueous phase was extracted with CH2Cl2 (3×35 mL), and the combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (25:1:1 CH2Cl2-MeOH—NH4OH) provided 28.0 mg (7%) of COMPOUND 398 as a white solid. 1H NMR (CDCl3) δ 1.55 (d, 7H), 3.72 (s, 2H), 3.79-3.97 (m, 4H), 4.08-4.15 (m, 1H), 4.61 (s, 2H), 7.00-7.03 (m, 1H), 7.12-7.22 (m, 4H), 7.30-7.34 (m, 2H), 7.39-7.548 (m, 2H), 7.66-7.73 (m, 1H), 8.63 (d, 1H, J=4.3 Hz). 13C NMR (CDCl3) δ 12.64, 46.30, 48.93, 56.11, 60.76, 63.68, 122.24, 122.64, 123.03, 126.86, 130.49, 132.06, 135.86, 137.63, 140.79, 140.79, 143.92, 149.44, 153.77, 161.45. ES-MS m/z 402 (M+H). Anal. Calcd. for C24H27N5O.0.6H2O.0.2CH2Cl2: C, 67.71; H, 6.71; N, 16.31. Found: C, 68.05; H, 6.75; N, 16.38.

Provenance & Evidence