Methyl iodide → 6-[(3-{[Tert-butyl(dimethyl)silyl]oxy}propyl)(methyl)amino]-2-chloro-5-fluoronicotinonitrile

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Reaction Steps

Sodium hydride (0.11 g, 4.65 mmol) was added to a solution of 6-[(3-{[tert-butyl(dimethyl)-I4-silyl]oxy}propyl)amino]-2-chloro-5-fluoronicotinonitrile (Example 309, 0.80 g, 2.33 mmol) in DMF (23.26 mL). The mixture was stirred at rt for 30 min, and then MeI (0.58 mL, 9.30 mmol) added. The reaction mixture was stirred at rt for 18 h, quenched with water, and the aqueous phase was extracted with ether. The combined ether extracts were washed with water, brine, and then dried (MgSO4), filtered, and concentrated under reduced pressure. The product (0.88 g, 99%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD3OD) δ 7.53 (d, 1H), 3.70-3.60 (m, 4H), 3.17 (d, 3H), 1.84-1.76 (m, 2H), 0.84 (s, 9H), 0.00 (s, 6H).

Provenance & Evidence