Lithium Hexamethyldisilazide → 5-(3-(2-(Methylthio)pyrimidin-4-yl)pyridin-2-yloxy)pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a brown solution of tris(dibenzylideneacetone)dipalladium (o) (0.68 g, 0.75 mmol), 2-(dicyclohexylphosphino)biphenyl (0.50 g, 1.4 mmol), and 4-(2-(6-chloropyridin-3-yloxy) pyridin-3-yl)-2-(methylthio)pyrimidine (1.9 g, 5.7 mmol) in 15 mL dioxane was added solid lithium bis(trimethylsilyl) amide (2.9 g, 17 mmol). Argon was bubbled through the reaction for 1 min, and then it was sealed and heated to 65° C. for 3.5 days. The reaction was cooled to ambient temperature, diluted with water, and acidified to a pH of about 1 with stirring, then brought to pH of about 5 with 6N NaOH. Dichloromethane was added and reaction was filtered through 2 cm Celite® in a frit, rinsing with MC and water. The layers were separated, and the organic layer was dried over anhyd. Na2SO4, filtered, and concentrated in vacuo. The material was diluted in 100 mL MC, and extracted 3×100 mL 1 N HCl. The aqueous layers were cooled to 0° C. and basified with 6 N NaOH to about pH of 10. The aqueous layer was extracted 3×100 mL with MC. The organic layers were combined, dried over anhdrous sodium sulfate, filtered, and concentrated in vacuo to a brown oil. The oil residue was purified by silica gel chromatography, 120 g, 0-50% MC-90/10 MC/MeOH, to afford 5-(3-(2-(methylthio)pyrimidin-4-yl)pyridin-2-yloxy)pyridin-2-amine as a yellow solid. MS m/z=312 [M+H]+. Calc'd for C15H13N5OS: 311.4.

Provenance & Evidence