2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → HCID 66813090, compound

Participants

Reaction Steps

4-Bromo-2-fluoroaniline (1.0 g, 5.3 mmol) was treated with N-phenylacetylproline (1.3 g, 5.52 mmol) and EEDQ as described in Example 1 to provide 2.1 g of N-(4-bromo-2-fluorophenyl)-1-(phenylacetyl)-L-prolinamide. A portion of this intermediate (0.51 g, 1.26 mmol) was suspended in 5 mL toluene and treated with 0.38 mL of trans-1,2-bis(tri-n-butylstannyl)ethylene (0.69 mmol, 0.55 equiv) followed by 0.029 g of Pd(PPh3)4. The reaction was sealed under nitrogen and heated to 100° C. for 2 hours. The mixture was then cooled to room temperature and stirred vigorously with an equal volume of aqueous saturated KF for 2 hours. Filtration through diatomaceous earth (Celite®) followed by extractive workup and HPLC purification provided the desired product. 1H NMR (DMSO-d6, 500 MHz, mixture of rotamers) δ 10.10 and 9.86 (s, 1H), 7.94 and 7.81 (m, 1H), 7.52 (m, 1H), 7.20-7.35 (m, 16H), 4.82 and 4.64 (m, 2H), 3.65 (m, 4H), 1.94-2.11 (m, 8H); LCMS (Rt=1.76 min, m/z 677.34).

Provenance & Evidence