反应详情

Under an inert atmosphere 3,5-dimethyl-isoxazole-4-sulfonic acid 7-(piperidin-4-ylmethyl-propyl-amino)-5,6,7,8-tetrahydro-naphthalen-2-yl ester (400 mg, 0.87 mmol), piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (199 mg, 0.87 mmol, 1 eq.), EDCI (166 mg, 0.87 mmol, 1 eq.), triethylamine (0.25 mL, 1.79 mmol, 2 eq.), and dichloromethane (35 mL) were combined. The mixture was stirred at room temperature for 48 h and then concentrated in vacuo. The residue was taken up in EtOAc (50 mL) and washed with water (30 mL), 1N NaOH (30 mL), brine (30 mL), and then dried (MgSO4). The solution was filtered and concentrated to afford a yellow oil. The oil was flash chromatographed on silica gel eluting with 20% acetone in hexanes to afford the protected amine as a foam (447 mg), which was deprotected with trifluoroacetic acid, as described herein, to afford 3,5-dimethyl-isoxazole-4-sulfonic acid 7-{[1-(piperidine-4-carbonyl)-piperidin-4-ylmethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-yl ester (320 mg), 114M+H]+=609.

1. concentrationconcentrated in vacuo
2. washwashed with water (30 mL), 1N NaOH (30 mL), brine (30 mL)
3. dry with materialdried (MgSO4)
4. filtrationThe solution was filtered
5. concentrationconcentrated
6. customto afford a yellow oil
7. customchromatographed on silica gel eluting with 20% acetone in hexanes