Hydrochloric Acid → HCID 86709320, compound

Participants

Reaction Steps

To a vial was added N-(7-bromo-3-chloro-5-(2-(cyanomethoxy)ethyl)-5H-chromeno[2,3-c]pyridin-5-yl)-2-methylpropane-2-sulfinamide (242 mg, 0.485 mmol) and HCl (4.0M solution in 1,4-dioxane, 0.970 mL, 3.88 mmol) in dioxane (4 mL). The mixture was stirred at RT for 20 mins, then quenched with 5 mL of a saturated aqueous solution of Na2CO3 and extracted into EtOAc. The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated to give the crude product as orange oil. The crude product was dissolved with 4 mL of toluene and trimethylaluminum solution (2M in toluene, 0.728 mL, 1.455 mmol) was added to the mixture (exothermic after addition). The mixture was heated to 90° C. in oil bath for 10 min, then quenched with Rochelle's salt (12 mL) at 0° C. and stirred overnight at RT. The reaction mixture was diluted with water and extracted with EtOAc (10 mL×2). The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated to give the crude material as orange oil. It was absorbed onto a plug of silica gel and purified by chromatography through a gold Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 30% to 50% to 80% DCM/MeOH/NH4OH (90/10/1) in 40% EtOAc in Heptane to provide (E)-7-bromo-3-chloro-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine as off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.03-2.22 (m, 4 H) 4.42 (s, 2 H) 6.18 (br. s., 2 H) 7.21 (d, J=8.51 Hz, 1 H) 7.39 (s, 1 H) 7.45-7.62 (m, 2 H) 8.36 (s, 1 H). The other stereoisomer is Example 3B in Table 1.

Provenance & Evidence