Ammonium Chloride → 2-(6-tert-Butyl-8-fluoro-1-oxo-1H-isoquinolin-2-yl)-4-iodo-pyridine-3-carbaldehyde

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To a solution of 6-tert-butyl-8-fluoroisoquinolin-1(2H)-one (225 mg, 1.03 mmol, Eq: 1.00) in THF (11.1 ml) was added lithium bis(trimethylsilyl)amide in THF (1 M) (1.13 ml, 1.13 mmol, Eq: 1.1) at room temperature. The reaction mixture was stirred for 20 min. at the same temperature. Then 2-fluoro-4-iodonicotinaldehyde (335 mg, 1.33 mmol, Eq: 1.3) in THF (5 mL) was added. The reaction mixture was heated to 65° C. and stirred for 3 h. Then the reaction was poured into an aqueous-saturated solution of NH4Cl (30 mL) and product was extracted with EtOAc (2×50 mL). The combined organic extracts were dried (Na2SO4) and evaporated under vacuum. Crude was diluted with CH2Cl2 (2 mL) and purified by chromatography (SiO2, Hex:AcOEt, 100% to 70% in 25 min) to afford the desired product (350 mg) as a light yellow powder. LC/MS, m/z 451[M+H]+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.39 (s, 9 H) 6.65 (dd, J=7.58, 2.02 Hz, 1 H) 7.21 (dd, J=13.64, 1.77 Hz, 1 H) 7.31 (d, J=1.77 Hz, 1 H) 7.55 (d, J=7.58 Hz, 1 H) 7.91 (d, J=5.05 Hz, 1 H) 8.28 (d, J=5.31 Hz, 1 H) 9.94 (s, 1 H).

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