Trifluoroacetic acid → (4aS,5R,7aS)-7a-(2-fluoro-5-(1H-imidazol-2-yl)phenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

Participants

Reaction Conditions

Reaction Steps

di-tert-Butyl{(4aS,5R,7aS)-7a-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl}imidodicarbonate (0.1 g, 0.17 mmol) was dissolved in 1,2-dimethoxyethane (1.5 mL), water (0.7 mL) and ethanol (0.5 mL). The resulting solution was heated to 100° C. and to it was added 2-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole (0.1 g, 0.31 mmol), cesium carbonate (0.33 g, 1.0 mmol) and dichloropalladium-triphenylphosphane (0.02 g, 0.03 mmol) and the reaction was stirred at 100° C. for 1 hour. The reaction mixture was cooled to room temperature, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (gradient 0-100% EtOAc in hexane) to give a mixture of mono and bis BOC products. 1H NMRs consistent with desired structures. The residues were combined and dissolved in DCM (2 mL). Trifluoroacetic acid (1 mL) was added and the solution stirred at room temperature for 1 hour. The solvents were removed in vacuo and saturated aqueous NaHCO3 added. The solution was extracted with DCM (×3). The combined organics were dried (MgSO4), filtered and concentrated to give the title compound (48 mg). 1H NMR (400 MHz, CDCl3) δ ppm: 7.76-7.89 (m, 2 H), 7.06-7.13 (m, 3 H), 4.57 (d, J=9.1 Hz, 1 H), 4.32-4.40 (m, 1 H), 3.81 (dd, J=8.8, 1.8 Hz, 1 H), 3.07 (dd, J=13.4, 3.5 Hz, 1 H), 2.71 (dd, J=13.3, 3.9 Hz, 1 H), 2.57-2.64 (m, 1 H), 1.37 (d. J=6.1 Hz, 3 H)

Provenance & Evidence