Potassium Phosphate, Tribasic → 4-(3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-7-isoquinolinyl)benzonitrile

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Reaction Steps

The product from Example 52G (0.2 g, 0.6 mmol), 4-cyanophenylboronic acid (0.22 g, 1.5 mmol), bis(triphenylphosphine)palladium dichloride (55 mg, 0.08 mmol), and potassium phosphate (7 mL, 0.2 M in water) were combined in isopropanol (7 mL) and heated at 60–65° C. for 7 hours in a sealed flask. The mixture was filtered through diatomaceous earth, the filtrate was concentrated in vacuo, and then partitioned between MTBE (10 mL) and water (10 mL). The organic layer was separated, washed with aqueous sodium bicarbonate solution (5%, 10 mL), and then extracted with a solution of 2M HCl (15 mL). The pH of the acidic aqueous layer was adjusted with base using potassium carbonate and extracted with isopropyl acetate (15 mL). The organic layer was evaporated in vacuo and the residue was chased with heptane (10 mL) to provide the title compound. 1H NMR (CDCl3) δ 1.12 (d, J=6.0 Hz, 3H); 1.37–1.50 (m, 1H); 1.64–1.85 (m, 2H); 1.85–1.98 (m, 1H); 2.26 (q, J=8.8. Hz, 1H); 2.32–2.43 (m, 1H); 2.50–2.60 (m, 1H), 3.09–3.34 (m, 4H); 7.56 (m, 1H); 7.73–7. 81 (m, 4H), 7.84–7.87 (m, 2H), 8.12 (m, 1H); 9.26 (s, 1H); HRMS Calcd. for [C23H23N3+H+]: 342.1970. Found: 342.1974.

Provenance & Evidence