3-fluoro-5-(3-methoxybenzoyl)-6-methyl-5,6-dihydrophenanthridine N-[1-(2',4'-difluoro-1,1'-biphenyl-2-yl)ethyl]-3-methoxybenzamide → 3-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]phenol

Participants

Reaction Conditions

Reaction Steps

3-fluoro-5-(3-methoxybenzoyl)-6-methyl-5,6-dihydrophenanthridine—N-[1-(2′,4′-difluoro-1,1′-biphenyl-2-yl)ethyl]-3-methoxybenzamide (1.29 g, 3.5 mmol) was dissolved in anhydrous THF (10 mL) and the vial was capped and purged with an inert atmosphere. Lithium bis(trimethylsilyl)amide (4.0 mL, 1 M in THF) was added to the solution and the mixture heated (70° C). The reaction progress was monitored by LCMS and heating was discontinued upon the expense of the starting material. The THF was removed and 2N aqueous HCl was added. The product was extracted with ethyl acetate (3×) and the combined organic phases were dried (Na2SO4), filtered, and concentrated to provide a crude oil. The residue was purified by flash column chromatography (Biotage® 40 Mi, 30-50% methyl tert-butylether in hexane) affording 1.0 g (82%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (d, J=6.76 Hz, 3 H) 3.71 (s, 3 H) 5.67 (s, 1 H) 6.77 (d, J=7.28 Hz, 2 H) 6.93 (s, 1 H) 7.03 (ddd, J=8.32, 2.73, 0.91 Hz, 1 H) 7.10 (td, J=8.71, 2.60 Hz, 1 H) 7.26 (t, J=7.93 Hz, 1 H) 7.40 (m, 3 H) 7.97 (d, J=7.54 Hz, 1 H) 8.01 (dd, J=8.84, 6.24 Hz, 1H); MS (ESI) m/z 348 ([M+H]+); HRMS: calcd for C22H18FNO2, 347.1322 (M), 348.13944 ([M+H]+); found (ESI_FT), 348.13903; Anal. Calcd for C22H18FNO2: C, 76.07; H, 5.22; N, 4.03. Found: C, 76.02; H, 5.32; N, 3.97.

Provenance & Evidence