1,2-Dichloroethane → HCID 86681735, compound

Participants

Reaction Steps

To a solution of 2-(4-(N-(2-morpholinoethyl)methylsulfonamido)-1H-indol-1-yl)acetic acid (100 mg, 0.262 mmol) in DCM (5 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (110 mg, 0.262 mmol), EDC (151 mg, 0.786 mmol) and DMAP (64.1 mg, 0.524 mmol) were added, and the mixture was reacted overnight at room temperature. The solvent was evaporated and the residue was partitioned between 1N HCl (10 ml) and EtOAc; the aqueous phase was extracted with EtOAc, the combined organic layers were dried over sodium sulfate and the solvent was removed under vacuum. Three flash chromatographic column on silica gel (DCM/MeOH 97/3) were required to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-(N-(2-morpholinoethyl)methylsulfonamido)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (21.4 mg, 0.027 mmol, 10.4% yield, MS/ESI+ 783.19 [MH]+, [αD]=+14.1, c=0.2 DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.50 (s, 2H), 7.34 (d, 1H), 7.07-7.21 (m, 5H), 6.90 (dd, 1H), 7.06 (t, 1H), 6.55 (d, 1H), 6.02 (dd, 1H), 5.25 (d, 1H), 5.10 (d, 1H), 3.91 (d, 2H), 3.80 (t, 2H), 3.46-3.54 (m, 4H), 3.41 (dd, 1H), 3.21 (dd, 1H), 3.09 (s, 3H), 2.32 (dd, 2H), 2.23-2.31 (m, 4H), 1.07-1.36 (m, 1H), 0.54-0.65 (m, 2H), 0.29-0.47 (m, 2H).

Provenance & Evidence