Diisopropylethylamine → Ethyl 10-((((3R)-3-fluoro-1-pyrrolidinyl)(oxo)acetyl)(methyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

Participants

Reaction Steps

To a stirred solution of ethyl 10-(methylamino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride (120 mg, 0.268 mmol) in DMF (4 mL) was added (R)-2-(3-fluoropyrrolidin-1-yl)-2-oxoacetic acid (130 mg, 0.804 mmol), diisopropylethylamine (0.281 mL, 1.607 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (306 mg, 0.804 mmol), 4-(dimethylamino)pyridine (DMAP) (9.82 mg, 0.080 mmol) and the resulting mixture stirred at room temperature for 16 h. The mixture was quenched with water and diluted with ethyl acetate, washed with 1N HCl, followed by sat.NaHCO3, dried (Na2SO4) filtered and concentrated. The crude product was purified on Biotage flash chromatography system using 30-100% ethyl acetate/hexane gradient to afford the title compound (80 mg, 0.144 mmol, 54% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ: 8.12-8.23 (2 H, m), 7.64 (1 H, t, J=7.48 Hz), 7.44-7.56 (2 H, m), 5.11-5.42 (1 H, m), 4.08-4.27 (2 H, m), 3.28-4.01 (9 H, m), 3.18 (3 H, d, J=3.05 Hz), 2.50 (1 H, brs), 1.72-2.37 (6 H, m), 0.99-1.11 (3 H, m). LCMS (M+H)=555.76.

Provenance & Evidence