4-Methylmorpholine → [Butyl-(4-{4-[(2R)-2-hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-piperidin-1-yl}-benzoyl)-amino]-acetic acid ethyl ester

Participants

Reaction Steps

A mixture of 4-(4-oxo-piperidin-1-yl)-benzoic acid (which was obtained in Example 151) (0.30 g, 1.37 mmol), 1-[3-(dimethylamino)propyl-3-ethylcarbodiimide hydrochloride (0.53, 2.74 mmol) and N-butylglycine ethyl ester (0.44 g, 2.7 mmol) was stirred in methylene chloride (70 mL). N-methylmorpholine (0.28 g, 2.74 mol) was added dropwise and the mixture was stirred overnight. The mixture was then washed with 0.05 N hydrochloric acid and water. The resulting solution was dried with magnesium sulfate and concentrated to give a gum. The gum was dissolved in dimethylformamide (15 mL) and then treated with N-[5-((1R)-2-amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (0.25 g, 1 mmol) (which was obtained in Example 10), sodium triacetoxyborohydride (0.85 g, 4 mmol) and acetic acid (0.3 mL). After stirring at room temperature under a nitrogen atmosphere for 2 hours the mixture was poured into a saturated aqueous sodium bicarbonate. The aqueous layer was extracted with n-butanol and the concentrated gum was purified by silica gel chromatography (methanol/methylene chloride) to give the title compound as a white solid; mp>60° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 0.70–1.60 (m, 12 H), 1.75–1.95 (m, 2 H), 2.50–3.50 (m, 7 H), 2.91 (s, 3 H), 3.60–3.75 (m, 2 H), 4.00–4.15 (m, 4 H), 4.47 (dd, J=8.0, 4.3 Hz, 1 H), 6.81 (d, J=8.5 Hz, 1 H), 6.90–7.00 (m, 3 H), 7.05–7.25 (m, 3 H); MS (ES) m/z: 591.3 (MH+); HRMS Calcd. for C29H43N4O7S (MH+): 591.2847. Found: 591.2840.

Provenance & Evidence