反应详情

A mixture of 4-(4-oxo-piperidine-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, 12H), 1.75-1.95 (m, 2H), 2.50-3.50 (m, 7H), 2.91 (s, 3H), 3.60-3.75 (m, 2H), 4.00-4.15 (m, 4H), 4.47 (dd, J=8.0, 4.3 Hz, 1H), 6.81 (d, J=8.5 Hz, 1H), 6.90-7.00 (m, 3H), 7.05-7.25 (m, 3H); MS (ES) m/z: 591.3 (MH+); HRMS Calcd. for C29H43N4O7S(MH+): 591.2847. Found: 591.2840.

1. washThe mixture was then washed with 0.05 N hydrochloric acid and water
2. dry with materialThe resulting solution was dried with magnesium sulfate
3. concentrationconcentrated
4. customto give a gum
5. stirringAfter stirring at room temperature under a nitrogen atmosphere for 2 hours the mixture
6. extractionThe aqueous layer was extracted with n-butanol
7. customthe concentrated gum was purified by silica gel chromatography (methanol/methylene chloride)