4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(5-(1-(Tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

A yellow solution of 5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridin-3-ylboronic acid (1.79 g, 5.71 mmol), 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9; 0.826 g, 5.71 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.; 0.202 g, 0.286 mmol), and potassium acetate (1.682 g, 17.14 mmol) in a mixture of dioxane (50 mL) and water (12.50 mL) was stirred under argon at 100° C. for 2 h. The yellow reaction mixture was subsequently partitioned between CH2Cl2 (200 mL) and half-saturated brine (100 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were dried over sodium sulfate and concentrated onto silica gel. Chromatographic purification (silica gel, 0 to 70% EtOAc/hexanes) provided 4-(5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (1.11 g, 2.94 mmol, 51.5% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J=9.3, 2.4 Hz, 1H), 8.19 (d, J=1.4 Hz, 1H), 5.49 (br. s., 2H), 3.63-3.76 (m, 2H), 2.96-3.07 (m, 1H), 2.55 (s, 3H), 1.34 (d, J=7.0 Hz, 3H), 0.85 (s, 9H), −0.02 (s, 3H), −0.03 (s, 3H). 19F NMR (377 MHz, CDCl3) δ −68.99 (d, J=6.0 Hz, 1F). m/z (ESI, +ve) 378.3 (M+H)+.

Provenance & Evidence