4-Toluenesulfonyl chloride → 4-Chloro-7-(3-methyloxetan-3-YL)-7H-pyrrolo[2,3-D]pyrimidine

Temperature

-50 °C

n-BuLi (6.6 mL of a 2.5 M solution in hexane, 16.5 mmol) was added to a solution of 2-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylpropane-1,3-diol (Preparation 217, 3.63 g, 15.0 mmol), in THF (80 mL) at −78° C. The reaction mixture was allowed to warm to −50° C. in 2 hours and TsCl (3.15 mg, 16.5 mmol) in THF (20 mL) was added to the reaction. The reaction was allowed to warm to 0° C. in 3 hours and additional n-BuLi (6.6 mL of a 2.5 M solution in hexane solution, 16.5 mmol) was slowly added to the reaction mixture. The mixture was stirred for 1 hour at 0° C. and stirred at 60° C. for 16 hours. After cooling to room temperature, the reaction was quenched by 50 mL of saturated aqueous NH4Cl solution and 100 mL of water, and the mixture was extracted with EtOAc (3×100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude residue was purified by column chromatogranhy on silica gel (gradient of EtOAc:heptane 20:80 to 70:30) to give a solid in 55% yield, 1.87 mg.

1. temperatureto warm to 0° C. in 3 hours
2. stirringstirred at 60° C. for 16 hours
3. temperatureAfter cooling to room temperature
4. customthe reaction was quenched by 50 mL of saturated aqueous NH4Cl solution and 100 mL of water
5. extractionthe mixture was extracted with EtOAc (3×100 mL)
6. dry with materialThe combined organic layers were dried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe crude residue was purified by column chromatogranhy on silica gel (gradient of EtOAc:heptane 20:80 to 70:30)
9. customto give a solid in 55% yield, 1.87 mg

ORD record

ord-f87a8712ffa74ed0b5d33d7c255ad819

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846698B2