Dimethyl Sulfoxide → (S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutanal

Temperature

-78 °C

To a cold (−78° C.) solution of oxalyl chloride (1.06 mL, 12.11 mmol) in dichloromethane (10 mL) was added dimethyl sulfoxide (1.43 mL, 20.18 mmol) dropwise. After stirring the mixture for 10 minutes at −78° C., a suspension of (2S)-2-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-3,3-dimethyl-butan-1-ol, 14a, (1.0 g, 4.04 mmol) in dichloromethane (10 mL) was added. The reaction mixture was stirred for 30 minutes at −78° C. and triethylamine (3.38 mL, 24.22 mmol) was added. The mixture was slowly warmed to 0° C. over 2 hours. The mixture was diluted into aqueous saturated NaHCO3 solution and extracted twice with EtOAc. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-15% EtOAc/CH2Cl2 gradient) to afford 680 mg of the desired product as a white solid.

1. additionwas added
2. stirringThe reaction mixture was stirred for 30 minutes at −78° C.
3. temperatureThe mixture was slowly warmed to 0° C. over 2 hours
4. extractionextracted twice with EtOAc
5. dry with materialThe combined organic phases were dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude residue was purified via silica gel chromatography (0-15% EtOAc/CH2Cl2 gradient)

ORD record

ord-c200cec491d840c28b76744f74629a5b

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051319B2