Acetyl chloride → N-(azetidin-3-yl)acetamide trifluoroacetate

100 mg of t-butyl azetidin-3-ylcarbamate was dissolved in ml of methylene chloride, and 225 mg of N,N-diisopropylethylamine was added. Under ice-cooling, the reaction mixture was added with 68 mg of acetyl chloride, and stirred at room temperature for 2 days. The reaction solution was diluted with ethyl acetate, and the organic layer was washed with 5% citric acid aqueous solution and brine in turn, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 146 mg of a brown oily matter. The obtained residue was dissolved in 2.5 ml of methylene chloride, and 1 ml of trifluoroacetic acid was added thereto, and the mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and then 66 mg of N-(azetidin-3-yl)acetamide trifluoroacetate was obtained. Subsequently, 33 mg of N-(azetidin-3-yl)acetamide trifluoroacetate, 148 mg of triethylamine, 100 mg of (S)-6-chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine, 28 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 56 mg of sodium t-butoxide and 30 mg of tris(dibenzylideneacetone)(chloroform)dipalladium were added in turn to 3 ml of degassed 1,4-dioxane, and the mixture was stirred at 90° C. for 2 hours under argon atmosphere. The reaction solution was diluted with ethyl acetate. The solution was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 17 mg of the objective compound as bright golden yellow powder.

1. additionwas added
2. temperatureUnder ice-cooling
3. washthe organic layer was washed with 5% citric acid aqueous solution and brine in turn
4. dry with materialdried over magnesium sulfate
5. distillationThe solvent was distilled off under reduced pressure
6. customto obtain 146 mg of a brown oily matter
7. stirringthe mixture was stirred at room temperature overnight
8. distillationThe solvent was distilled off under reduced pressure

ORD 기록

ord-be55a6e2d02245248be5eac40f692cde

출처 데이터셋

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08586591B2