Hydrochloric Acid → (2S)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-3-(2-hydroxyethoxy)-N-(5-methylpyridin-2-yl)propanamide

Participants

Reaction Conditions

Reaction Steps

Hydrochloric acid (10%, 2 mL) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AP3) (335 mg, 0.47 mmol) in methanol (30.0 mL) at 0° C. The resulting solution was stirred at 0° C. for 10 minutes and allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was quenched with saturated NH4Cl (25 mL) and most of the MeOH was removed by evaporation. The aqueous residue was extracted with EtOAc (3×25 mL), the organic layer was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents to afford the product (67.0 mg, 30.1%). 1H NMR (400 MHz, CDCl3) δ2.31 (s, 3H), 3.73-3.85 (m, 4H), 4.20-4.35 (m, 2H), 6.06 (t, 1H), 7.49-7.63 (m, 4H), 7.68 (d, 1H), 8.05 (s, 1H), 8.09-8.22 (m, 2H), 8.68 (s, 1H), OH not observed; m/z (ESI+) (M+H)+=470.41; HPLC tR=1.80 min

Provenance & Evidence