Potassium Carbonate → 2-(4-Ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide (212 mg, 0.5 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (126 mg, 0.5 mmol), and potassium acetate (97 mg, 0.99 mmol) in 1,4-dioxane (2.5 mL) was added PdCl2(dppf)-CH2Cl2 adduct (40 mg, 0.05 mmol). The reaction mixture was purged with nitrogen and heated at 120° C. for 4 h. The reaction mixture was cooled and 7-bromo-3-methylquinoline (110 mg, 0.5 mmol) and 2M aq K2CO3 (0.55 mL, 1.09 mmol) were added. The reaction mixture was purged with nitrogen and was heated with stirring at 100° C. for 1 h. The reaction mixture was diluted with dichloromethane (60 mL) and any salts were filtered away. The organic mixture was filtered through a plug of celite and sodium sulfate. The filtrate was treated with a small amount of Silicycle Si-thiol resin for 30 min. The mixture was filtered and concentrated in vacuo. Purification of the residue by reverse phase HPLC (10-70% acetonitrile:water with 0.1% NH4OH) provided the title product (131 mg, 51% yield). MS(ES)+ m/e 491 [M+H]+; 1H NMR (400 MHz, CD2Cl2) δ ppm 1.12 (t, J=7.20 Hz, 3 H) 1.63-1.86 (m, 3 H) 1.86-2.05 (m, 2 H) 2.29-2.41 (m, 1 H) 2.53-2.59 (m, 3 H) 2.59-2.74 (m, 2 H) 2.79 (d, J=11.62 Hz, 1 H) 3.41 (q, J=7.33 Hz, 2 H) 3.95-4.10 (m, 2 H) 4.52 (s, 1 H) 5.87 (d, J=4.04 Hz, 1 H) 7.28 (d, J=3.54 Hz, 1 H) 7.41-7.50 (m, 1 H) 7.55 (dd, J=11.37, 1.77 Hz, 1 H) 7.62 (dd, J=7.96, 1.89 Hz, 1 H) 7.82 (dd, J=8.46, 1.89 Hz, 1 H) 7.90 (d, J=8.59 Hz, 1 H) 7.97-8.05 (m, 1 H) 8.27-8.36 (m, 1 H) 8.83 (d, J=2.27 Hz, 1 H).

Provenance & Evidence