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

Participants

Reaction Steps

To a solution of t-butyldimethylsilyl chloride (0.73 g, 4.79 mmol) in CH2Cl2 (21 mL) was added 2-chloro-5-fluoro-6-[(3-hydroxypropyl)amino]nicotinonitrile [prepared as in Example 302] and starting from 2,6-dichloro-5-fluoronicotinonitrile] (1.0 g, 4.35 mmol), followed by Et3N (0.48 g, 4.79 mmol) and DMAP (0.01 g, 0.09 mmol). The resulting cloudy mixture was stirred at rt for 18 h, and then diluted with CH2Cl2. The organic layer was washed with water, dried (MgSO4), filtered, and then concentrated under reduced pressure. The product (1.47 g, 98%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc) as a white solid. 1H NMR (400 MHz, CD3OD) δ 7.46 (d, 1H), 3.67 (t, 2H), 3.49 (t, 2H), 1.77 (qt, 2H), 0.84 (s, 9H), 0.00 (s, 6H).

Provenance & Evidence