Tetrahydrofuran → HCID 86709319, compound

Participants

Reaction Steps

A 100 mL RBF was charged with N-(7-bromo-3-chloro-5-(2-hydroxyethyl)-5H-chromeno[2,3-c]pyridin-5-yl)-2-methylpropane-2-sulfinamide (625 mg, 1.359 mmol), tetrabutylammonium hydrogen sulfate (138 mg, 0.408 mmol), THF (6.80 mL), and bromoacetonitrile (0.852 mL, 12.23 mmol) to give a cloudy, light brown solution. The resulting solution was stirred vigorously for 5 min. Then a 2N aq. solution of sodium hydroxide (13.600 mL, 27.2 mmol) was added in one portion. The solution changed into dark brown color. 3 Hrs later, LCMS showed an incomplete conversion (SM: product=1:1.5). 1 additional molar equivalent of BrCH2CN was added, and the mixture was stirred for 1 hr. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated to give the crude material as a brown solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 25 to 40 to 80% DCM/MeOH/NH4OH (90:10:1) in 40% EtOAc in heptane to yield N-(7-bromo-3-chloro-5-(2-(cyanomethoxy)ethyl)-5H-chromeno[2,3-c]pyridin-5-yl)-2-methylpropane-2-sulfinamide as off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.12 (m, 9 H) 2.59 (d, J=9.49 Hz, 2 H) 3.03 (s, 2 H) 4.10 (s, 2 H) 6.52 (s, 1 H) 7.10-7.20 (m, 1 H) 7.51-7.59 (m, 1 H) 7.72-7.80 (m, 1 H) 7.93 (d, J=2.45 Hz, 1 H) 8.33-8.40 (m, 1 H).

Provenance & Evidence