HCID 72203421, compound → HCID 72203420, compound

Participants

Reaction Steps

A solution of 6-(3,6-dihydro-2h-pyran-4-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Example 44, 80 mg, 0.180 mmol) in acetic acid (5 mL) was hydrogenated in the presence of PtO2 (16 mg) at RT and atmospheric pressure for 67 h. The RM was filtered through Celite® and the solvent was evaporated off under reduced pressure to give the crude product which was purified by reverse phase chromatography (MPLC, Lichroprep® 15-25 μm column, water+0.1% formic acid/MeCN+0.1% formic acid, gradient 5% to 39% MeCN+0.1% formic acid). Fractions containing the pure product were combined, basified with NaHCO3 and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative TLC (Silica gel 60 F 254, 0.5 mm, eluent was DCM/MeOH 19:1). The product was dissolved with MeCN, filtered and the filtrate was evaporated off under reduced pressure to afford the title compound as white crystalline solid. HPLC (Condition 3) tR=5.09 min, UPLC-MS (Condition 2) m/z=444.4 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.54-1.65 (m, 2H) 1.85-2.02 (m, 2H) 2.88-3.03 (m, 1H) 3.19-3.28 (m, 2H) 3.80-3.93 (m, 2H) 7.37 (d, J=8.99 Hz, 2H) 7.86 (m, J=9.00 Hz, 2H) 8.23 (d, J=1.96 Hz, 1H) 8.96 (s, 2H) 9.15 (d, J=1.95 Hz, 1H) 9.30 (s, 1H) 10.56 (s, 1H).

Provenance & Evidence