Water → Ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

To a stirred solution of ethyl 10-amino-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride (2.4 g, 5.53 mmol) in DMF (50 mL) as added 2-(dimethylamino)-2-oxoacetic acid (1.295 g, 11.06 mmol), diisopropyl-ethylamine (5.80 mL, 33.2 mmol) and the resulting mixture was stirred at room temperature for 3 h. Water was then added and the mixture extracted with ethyl acetate (2×200 mL). The organic solution was washed with 1N HCl (50 mL), dried (Na2SO4), filtered and concentrated. The crude material was triturated with ethyl acetate/hexane to afford the title compound (2.5 g, 5.04 mmol, 91% yield) as a light yellow solid. 1H NMR (500 MHz, CDCl3) δ: 9.33 (1 H, brs), 8.18 (2 H, d, J=7.02 Hz), 7.64 (1 H, t, J=7.48 Hz), 7.50 (2 H, t, J=7.93 Hz), 4.29 (2 H, q, J=7.02 Hz), 4.17 (2 H, d, J=3.66 Hz), 3.34 (3 H, s), 3.03 (3 H, s), 2.88-3.00 (2 H, m), 2.50 (1 H, brs), 1.93-2.10 (4 H, m), 1.73-1.82 (2 H, m), 1.18 (3 H, t, J=7.17 Hz). LCMS (M+H)=497.79.

1. extractionthe mixture extracted with ethyl acetate (2×200 mL)
2. washThe organic solution was washed with 1N HCl (50 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude material was triturated with ethyl acetate/hexane

ORD record

ord-d795e993b573435bb645218cf4264c49

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2