Water → 2-Chloro-5-morpholinopyridin-3-amine

Temperature

60 °C

A mixture of 3-amino-5-bromo-2-chloropyridine (2.0 g, 9.7 mmol), morpholine (1.3 mL, 14.9 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-triisopropyl-biphenyl, (X-Phos) (0.37 g, 0.8 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.36 g, 0.39 mmol) in dry THF (15.0 mL) was degassed by nitrogen. To this mixture was added 1.0M lithium bis(trimethylsilyl)amide in THF (25 mL) dropwise, and the resulting reaction was heated to 60° C. After 2.5 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic layers were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (0-20% EtOAc in hexanes) to afford an off-white solid as 2-chloro-5-morpholinopyridin-3-amine. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.35 (1H, d, J=2.7 Hz), 6.67 (1H, d, J=2.7 Hz), 5.33 (2H, s), 3.79 (4H, m), 3.11 (4H, m).

1. customwas degassed by nitrogen
2. additionTo this mixture was added 1.0M lithium bis(trimethylsilyl)amide in THF (25 mL) dropwise
3. customthe resulting reaction
4. temperaturethe reaction was cooled to rt
5. extractionAfter extracting twice with EtOAc and twice with DCM
6. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
7. filtrationAfter filtration and concentration
8. customthe residue was purified on basic alumina (0-20% EtOAc in hexanes)

ORD record

ord-02195e2a2d564d97886f9bcb8c5212e9

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940724B2