反应详情

To a stirred warm (60° C.) solution of 3-aminopiperidine dihydrochloride (150 mg, 0.867 mmol), paraformaldehyde (34 mg, 1.04 mmol) and triethylamine (0.3 mL, 2.14 mmol) in methanol (5 mL) was added N-(3,4-dichloro-benzyl)-2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-methyl-acetamide (300 mg, 0.872 mmol). After 1 h, the reaction mixture was cooled and purified by preparative HPLC using a C18 column and water/methanol (0.001 mM HCl) as eluent. The fractions containing the desired product were combined, concentrated and lyophilized to give the corresponding hydrochloride salt of the title compound as a white powder (162 mg, 43% yield). 1HNMR (500 MHz, DMSO-d6) δ: 11.06 (1H, br s), 9.35 (1H, d, J=10.1 Hz), 9.10–8.99 (1H, m), 7.62 (1H, d, J=8.2 Hz), 7.52 (1H, s), 7.29–7.20 (1H, br s), 4.59 (2H, d, JAB=15.7 Hz), 4.34–3.88 (4H, m), 3.40–2.73 (6H, m), 1.90–1.74 (4H, m). HRMS calcd for C18H22Cl2N3O3 (M+H): 398.1038; found: 398.1042.

1. temperaturethe reaction mixture was cooled
2. custompurified by preparative HPLC
3. additionThe fractions containing the desired product
4. concentrationconcentrated