Potassium Carbonate → 2-(4-(3-Cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)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 (202 mg, 0.47 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (120 mg, 0.47 mmol), and potassium acetate (93 mg, 0.94 mmol) in 1,4-dioxane (2.5 mL) was added PdCl2(dppf)-CH2Cl2 adduct (38.5 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-bromoquinoline-3-carbonitrile (110 mg, 0.47 mmol) and 2M aq K2CO3 (0.52 mL, 1.04 mmol) were added. The reaction mixture was purged with nitrogen and 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 and 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) afforded the title product (138 mg, 55% yield). MS(ES)+ m/e 502 [M+H]+; 1H NMR (400 MHz, CD2Cl2) δ ppm 1.13 (t, J=7.20 Hz, 3 H) 1.65-1.84 (m, 2 H) 1.86-2.04 (m, 2 H) 2.25-2.40 (m, 1 H) 2.55-2.74 (m, 2 H) 2.75-2.87 (m, 1 H) 3.18 (s, 2 H) 3.41 (q, J=7.07 Hz, 2 H) 3.92-4.11 (m, 2 H) 4.56 (s, 1 H) 5.62 (d, J=3.54 Hz, 1 H) 7.28 (d, J=4.29 Hz, 1 H) 7.49 (t, J=7.71 Hz, 1 H) 7.58 (dd, J=11.12, 1.77 Hz, 1 H) 7.65 (dd, J=8.08, 1.77 Hz, 1 H) 8.00 (dd, J=8.59, 1.77 Hz, 1 H) 8.06 (d, J=8.34 Hz, 1 H) 8.43 (s, 1 H) 8.63 (d, J=2.02 Hz, 1 H) 9.10 (d, J=2.02 Hz, 1 H).

Provenance & Evidence