Azobisisobutyronitrile → 2-Chloro-7-methylthieno(3,2-d)pyrimidine

Temperature

100 °C

A mixture of 2-chloro-7-methyl-thieno[3,2-d]pyrimidine (1.8 g), N-bromosuccinimide (1.8 g), 2,2′-azobis(2-methylpropionitrile) (0.1 g) in carbon tetrachloride (50 mL) was heated at reflux for 1 hour. The resulting mixture was cooled, the solid was filtered off and the filtrate was evaporated under reduced pressure. The residue was dissolved in acetonitrile (20 mL) and diisopropylethylamine (2.0 mL) was added, followed by pyridine-N-oxide (3 g) and the resulting mixture was heated at 100° C. for 30 minutes. The reaction mixture was cooled, diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (hexane/EtOAc) to afford 0.25 g of 2-chloro-thieno[3,2-d]pyrimidine-7-carbaldehyde and 1 g of 2-chloro-7-methyl-thieno[3,2-d]pyrimidine starting material.

1. temperaturewas heated
2. temperatureat reflux for 1 hour
3. temperatureThe resulting mixture was cooled
4. filtrationthe solid was filtered off
5. customthe filtrate was evaporated under reduced pressure
6. dissolutionThe residue was dissolved in acetonitrile (20 mL)
7. additiondiisopropylethylamine (2.0 mL) was added
8. temperatureThe reaction mixture was cooled
9. additiondiluted with ethyl acetate
10. washwashed with water and brine
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltered
13. customevaporated under reduced pressure
14. customThe crude residue was purified by flash chromatography (hexane/EtOAc)

ORD record

ord-b8846945861b4c4f805ba72171235b13

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09255110B2