Sodium hydride → 2-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-4-iodo-pyridine-3-carbaldehyde

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Reaction Steps

In a 100 mL round-bottomed flask, 6-tert-butylphthalazin-1(2H)-one (700 mg, 3.46 mmol, Eq: 1.00) was combined with THF (30 ml) to give a colorless solution. Sodium hydride (152 mg, 3.81 mmol, Eq: 1.1) was added. The reaction mixture was stirred at ambient temperature for 15 min. A solution of 2-fluoro-4-iodonicotinaldehyde (956 mg, 3.81 mmol, Eq: 1.1) in 10 mL THF was the added to the reaction mixture and it was stirred at ambient temperature for 3.5 h. The reaction was not complete. An additional 50 mg NaH was added. The reaction was stirred for an additional 1.5 h, before addition of saturated NH4Cl. The reaction mixture was poured into 100 mL H2O and extracted with dichloromethane (5×50 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 10% to 60% EtOAc in hexanes) to afford slightly impure product. The product was triturated with EtOAc to afford the desired product as a cream solid. The combined filtrate and washes from the trituration were concentrated, re-purified by flash chromatography (silica gel, 80 g, 10% to 60% EtOAc in hexanes) and trituration with EtOAc to afford additional product as a cream solid. The two batches of product were combined to afford 320 mg of the desired product. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9 H) 7.74 (d, J=1.89 Hz, 1 H) 7.89 (dd, J=8.50, 1.70 Hz, 1 H) 8.02 (d, J=5.29 Hz, 1 H) 8.28-8.44 (m, 3 H) 9.92 (s, 1 H) (M+H)+=434 m/e.

Provenance & Evidence