Hydrochloric Acid → (R)-1-(1-(2-Hydroxy-3-(pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one hydrochloride

Participants

Reaction Conditions

Reaction Steps

To (S)-1-(1-(oxiran-2-ylmethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-pyridin-2(1H)-one (200 mg, 0.48 mmol) in tetrahydrofuran (5 mL) was added LiClO4 (775 mg, 7.28 mmol) followed by pyrrolidine (0.41 mL, 4.9 mmol). The reaction mixture was heated in a 45° C. oil bath for 4.5 h. The reaction mixture was cooled to ambient temperature, diluted with dichloromethane (50 ml), washed with water (25 mL) and brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. The material was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH to 90:9:1 CH2Cl2/MeOH/conc. NH4OH). The dried residue (197 mg, 0.41 mmol) was dissolved in dichloromethane (10 mL) and HCl (1.25 M solution in methanol, 0.36 mL, 0.45 mmol) was added. The mixture was concentrated under reduced pressure and dried to afford the title compound (194 mg, 78%) as a yellow solid: mp 116-119° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.65 (br s, 1H), 8.21 (s, 1H), 8.02-8.00 (m, 2H), 7.89-7.82 (m, 5H), 7.47 (dd, J=9.0, 2.0 Hz, 1H), 6.89 (d, J=2.0 Hz, 1H), 6.74 (dd, J=7.0, 2.0 Hz, 1H), 5.75 (br s, 1H), 4.57-4.47 (m, 2H), 4.33 (br s, 1H), 3.56-2.90 (br m, 6H), 1.89 (br s, 4H); ESI MS m/z 483 [M+H]+; HPLC (Method B)>99% (AUC), tR=14.5 min; [α]23D +10.8° (c 0.11, Methanol).

Provenance & Evidence