Chlorosuccinimide → 2,6-Dichloro-4-morpholinothieno[3,2-d]pyrimidine

Temperature

-40 °C

n-Butylithium (1.6 mL, 3.914 mmol) in 2.5 M hexane solution was added to a mixture of 2-chloro-4-morpholinothieno[3,2-d]pyrimidine 4 (500 mg, 1.957 mmol) in 10 mL of THF at −78° C. The reaction mixture was allowed to warm to −40° C. and stirred for 40 min. A solution of N-chlorosuccinimide (523 mg, 3.914 mmol) in 8 mL of THF was added dropwise. After the addition was completed. The reaction mixture was brought to room temperature and stirred for 2 h. The reaction was monitored by LC/MS. The mixture was diluted with ether and extracted with 1N HCl (2×60 mL). The aqueous layer was then basified and extracted with ethyl acetate (2×100 mL). The organic layer was washed with H2O (60 mL), dried over MgSO4, filtered and evaporated. The crude product was purified by ISCO Combiflash (5˜50% ethyl acetate/hexane) to afford 2,6-dichloro-4-morpholinothieno[3,2-d]pyrimidine (284 mg, 50%).

1. additionAfter the addition
2. customwas brought to room temperature
3. stirringstirred for 2 h
4. extractionextracted with 1N HCl (2×60 mL)
5. extractionextracted with ethyl acetate (2×100 mL)
6. washThe organic layer was washed with H2O (60 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customThe crude product was purified by ISCO Combiflash (5˜50% ethyl acetate/hexane)

ORD record

ord-fafda2db56d04a0abe025f15efe52ebc

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450315B2