p-Toluenesulphonyl cyanide → 4-Chlorothieno[3,2-d]pyrimidine-6-carbonitrile

Temperature

-78 °C

To a suspension of compound 6.2 (5.0 mmol) in dry THF (25.0 mL) was added lithium diisopropylamide (“LDA”; 6.0 mmol; 2.0 M in heptane/THF/ethylbenzene) at −78° C. under an atmosphere of N2. After stirring at −78° C. for 30 minutes, the mixture was transferred to a pre-cooled solution of TsCN (8.0 mmol) in dry THF (10 mL) at −78° C. The resulting mixture was slowly warmed to room temperature and stirred for several hours. The reaction was quenched by the addition of several drops of saturated ammonium chloride and then concentrated. The residue was diluted with saturated sodium bicarbonate and extracted with EtOAc. The organic layers was dried, concentrated and purified by flash column chromatography on silica gel to provide 4-chloro-thieno[3,2-d]pyrimidine-6-carbonitrile c (compound 47.1) in 20% yield. EIMS (m/z): calcd. for C7H2CN3S (M+)+H 195.97. found 196.00.

1. temperatureThe resulting mixture was slowly warmed to room temperature
2. stirringstirred for several hours
3. customThe reaction was quenched by the addition of several drops of saturated ammonium chloride
4. concentrationconcentrated
5. additionThe residue was diluted with saturated sodium bicarbonate
6. extractionextracted with EtOAc
7. customThe organic layers was dried
8. concentrationconcentrated
9. custompurified by flash column chromatography on silica gel

ORD record

ord-2589d3712dd441e9b816930534a79038

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07601725B2