Triethylamine → (1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-5-(7-methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1lambda6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of (7-methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-acetic acid (0.38 g, 1.20 mmol) and (1S,2R,3S,4R)-3-(4-fluoro-benzylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester (0.42 g, 1.44 mmol) in N,N-dimethylformamide (4 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.34 g, 1.80 mmol). The reaction was stirred at 25° C. for 15 min before triethylamine (1 mL, 7.20 mmol) was added. The reaction was then stirred at 75° C. overnight. The reaction was cooled to 25° C. and quenched with 1.0 M aqueous hydrochloric acid solution (5 mL). The resulting mixture was extracted with dichloromethane (3×10 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-50% ethyl acetate in hexanes) to afford the desired product, (1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-5-(7-methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.44 g, 0.80 mmol, 67%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.18-1.78 (6H, m), 2.55-2.56 (1H, m), 2.82-2.86 (2H, m), 3.45 (3H, s), 4.21 (1H, d, J=15.6 Hz), 4.79 (2H, s), 4.82 (2H, s), 5.15 (1H, d, J=15.2 Hz), 7.00-7.07 (3H, m), 7.20 (2H, dd, J=5.6, 8.8 Hz).

Provenance & Evidence