2,3-Butanediol → 4-Chloro-6-[5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-pyrimidin-2-ylamine

To a mixture of 5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenylboronic acid (1.6 g, 6.3 mmol), 4,6-dichloro-pyrimidin-2-ylamine (1.2 g, 7.6 mmol), palladium acetate (211 mg, 0.95 mmol), and dimethyl ethylene glycol (100 ml), degassed with argon, was added a solution of sodium carbonate (4.0 g, 37.8 mmol) in water (15 ml) followed by triphenylphosphine (495 mg, 1.9 mmol). After stirring for 12 hours, the mixture was filtered through a pad of celite under suction. The organic layer was separated from the filtrate and dried over magnesium sulfate. The mixture was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:5 followed by 1:4) to give 4-chloro-6-[5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-pyrimidin-2-ylamine, which was dissolved in ethyl acetate (10 ml) and treated with a solution of hydrogen chloride in dioxane (4 M, 2.5 ml). The solid was filtered to provide the hydrochloride salt of 4-chloro-6-[5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-pyrimidin-2-ylamine (500 mg, 20% yield). 1H NMR (CD3OD) δ 4.78 (q, 2H, J=8.5 Hz, CH2), 7.31-7.33 (m, 2H, Ar), 7.65 (dd, 1H, J=8.9 Hz, J=2.8 Hz, Ar), 7.82 (d, 1H, J=2.6 Hz, Ar).

1. customdegassed with argon
2. filtrationthe mixture was filtered through a pad of celite under suction
3. customThe organic layer was separated from the filtrate
4. dry with materialdried over magnesium sulfate
5. customThe mixture was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:5 followed by 1:4)

ORD record

ord-5f52e4dd7ec94562be53befaa13e0729

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419984B2