90% |
Stage #1: N-acetylpiperidine-4-carboxaldehyde; 4-amino-N-(3,4-dimethylphenyl)benzenesulfonamide With scandium tris(trifluoromethanesulfonate) In acetonitrile at 20℃; for 1h; Molecular sieve; Inert atmosphere;
Stage #2: 2,3-dihydro-2H-furan In acetonitrile at 20℃; Inert atmosphere; |
Preparation of 4-(l-acetylpiperidin-4-yl)-N -(3,4-dimethylphenyl)- 2,3,3a,4,5,9b-hexahydrofuran[3,2-c]quinolone-8-sulfonamine (69L57).
Compound 4-amino-N-(3,4-dimethylphenyl)benzenesulfoiiamide (2) (0.41 g, 1.48 mmol), l-acetylpiperidine-4-carbaldehyde (0.23 g, 1.48 mmol), Sc(OTf)3 (0.15 g, 0.30 mmol) and 4A molecular sieves (1 g) were mixed together and dissolved in anhydrous CH3CN (10 mL) at room temperature under argon. The reaction mixture was stirred for one hour at room temperature. 2,3-Dihydrofuran (0.21 g, 2.97 mmol) was then added via a syringe. The resulted mixture was stirred at room temperature under argon overnight. The reaction was quenched by adding 50 mL of water at room temperature and neutralized by adding NaHCO3. The solution was extracted with ethyl acetate (3x50 mL). The extracts were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to dryness. The solid residue was purified by column chromatography (silica gel, CH2CI2/MeOH = 19/1 v/v) to give a white solid product (0.62 g, 86% yield). (90% tram- isomer) : 1H NMR (400 MHz,, DMSQ-d6) d 9.64 (s, 1H), 7.47 (d, J = 1.6 Hz, 1H), 7.24 (dd, J 1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.82 (s, 1H), 6.77 (d, J 8.0 Hz, HI), 6.69 (d, J = 8.4 Hz, 1H), 6.12 (d, J = 6.4 Hz, 1H), 4.94 (d, J = 7.6 Hz, 1H), 4.42 (d, J = 8.4 Hz, 1H), 3.787- 3.82 (m, 1H), 3.72-3.64 (m, 1H), 3.49-3.44 Cm, 1H), 3.19 (dd, J 1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 3.03-2.97 (m, 1H), 2.09 (s, 6H), 1.99 (s, 3H), 1.86-1.73 (m, 3H), 1.63-1 52 (m, 3H), 1.14-1.07 (m, 2H) HRMS (ESI) calcd for C26H34N3O4S: 484.2270 [M + H]+, found 484.2268. |