Pyridine → HCID 89573878, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of rel-N-((4aR,10bS)-8-Fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-yl)benzamide from step F5 (1.27 g, 3.56 mmol), pyridine (1.0 mL, 12.36 mmol), and hydroxylamine methyl ether hydrochloride (1.0 g, 12.0 mmol) in ethanol (100 mL) was heated at 50° C. for 24 h. The mixture was concentrated under reduced pressure. The residue was diluted with saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using silica gel column chromatography (5-10% MeOH/dichloromethane) to afford rel-(4aR,10bS)-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-amine (644 mg, 2.50 mmol, 70% yield) as a viscous yellow oil. LCMS (M+H)+=253.1. 1H NMR (500 MHz, chloroform-d) δ 7.59 (dd, J=8.8, 6.6 Hz, 1H), 6.73-6.65 (m, 1H), 6.51 (dd, J=10.1, 2.6 Hz, 1H), 4.40 (dd, J=11.4, 2.8 Hz, 1H), 4.21 (dd, J=11.4, 5.7 Hz, 1H), 3.15-3.02 (m, 2H), 2.14 (dddd, J=8.4, 5.7, 3.7, 2.9 Hz, 1H), 1.60 (s, 3H).

Provenance & Evidence