1,2-Dichloroethane → HCID 86681705, compound

Participants

Reaction Steps

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (188 mg, 0.449 mmol), DMAP (110 mg, 0.897 mmol) and EDC (129 mg, 0.673 mmol) in DCM (10 ml), 2-(1,3-dioxo-5-(N-(2-(piperidin-1-yl)ethyl)methylsulfonamido)isoindolin-2-yl)acetic acid hydrochloride (200 mg, 0.449 mmol) was added portion wise over 5 hours, and the resulting mixture was stirred at room and for 96 hours. The solvent was removed and the crude was purified by silica gel chromatography (EtOAc/DCM 2/1 then DCM/MeOH 100/3). The resulting white solid was triturated with EtOH and recovered by filtration affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(1,3-dioxo-5-(N-(2-(piperidin-1-yl)ethyl)methylsulfonamido)isoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (190 mg, 0.234 mmol, 52.2% yield, LC-MS purity (BPI): 98.3%, MS/ESI+ 811.21 [MH]+, [αD]=+28.12, c=0.653 DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.97 (d, 1H), 7.95 (d, 1H), 7.89 (dd, 1H), 7.19 (d, 1H), 7.09 (d, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.43 (s, 2H), 3.91-4.04 (m, 2H), 3.88 (t, 2H), 3.38 (dd, 1H), 3.23 (dd, 1H), 3.15 (s, 3H), 2.35 (t, 2H), 2.17-2.31 (m, 4H), 1.03-1.53 (m, 7H), 0.49-0.68 (m, 2H), 0.28-0.46 (m, 2H).

Provenance & Evidence