反应详情

5-{4-(4-Oxo-piperidin-1-yl)-benzyl]-thiazolidine-2,4-dione (which was obtained in Example 38) (0.15 g, 0.5 mmol) and (2S)-1-amino-3-phenoxy-propan-2-ol (which was obtained in Example 3) (0.12 g, 0.75 mmol) were mixed in N,N-dimethylformamide (15 mL) and then treated with sodium triacetoxyborohydride (0.16 g, 0.75 mmol) and acetic acid (0.045 g, 0.75 mmol). After stirring at room temperature under a nitrogen atmosphere for one day the mixture was quenched with 1N NaOH and then poured into a saturated aqueous NaHCO3. The aqueous solution was extracted with 1-butanol and the combined organic layers were concentrated. The residue was purified by preparative thin layer chromatography (10% MeOH/CH2CH2) to give the title compound as a pale yellowish solid; mp 218–220° C.; 1H NMR (300 MHz, DMSO-d6) δ 1.30–1.60 (m, 2 H), 1.80–2.00 (m, 2 H), 2.50–3.00 (m, 5 H), 3.00–3.50 (m, 3 H), 3.50–3.70 (m, 2 H), 3.85–4.00 (m, 3 H), 4.48 (dd, J=9.8, 3.8 Hz, 1 H), 6.85 (d, J=8.6 Hz, 2 H), 6.90–6.97 (m, 3 H), 7.04 (d, J=8.6 Hz, 2 H), 7.25–7.38 (m, 3 H); MS (ES) m/z: 456.0 (MH+); HRMS Calcd. for C24H29N3O4S (M+): 455.1878. Found: 455.1880.

1. customwas quenched with 1N NaOH
2. additionpoured into a saturated aqueous NaHCO3
3. extractionThe aqueous solution was extracted with 1-butanol
4. concentrationthe combined organic layers were concentrated
5. customThe residue was purified by preparative thin layer chromatography (10% MeOH/CH2CH2)