Acetonitrile → 3-Amino-7-(cyclopropylmethyl)-2-nitrothieno[2,3-b]pyridin-6(7H)-one

Temperature

-78 °C

A mixture of (isothiocyanatomethyl)cyclopropane (3.3 g, 31.13 mmol) (J. Org. Chem., 1972, 37, 1162-1168) and acetonitrile (4 ml) was dissolved in dry THF (50 ml) and cooled to −78° C. under a nitrogen atmosphere. A solution of sodium bis(trimethylsilyl)amide in THF (1.0M, 66 ml, 66 mmol) was added over 10 min and the reaction mixture then allowed to warm to r.t. over 2 h. EtOH (50 ml) and N,N-dimethyluracil (4.8 g, 34.2 mmol) were added and the mixture heated to reflux for 24 h. The mixture was cooled and concentrated in vacuo. The residue was dissolved in acetonitrile (50 ml) and bromonitromethane (7.30 g, 46.7 mmol) was added. The mixture was heated to 55° C. for 18 h then cooled to r.t. and diluted with ice/water (100 ml). The resulting solid was isolated by filtration to give the title compound as a brown solid (3.3 g, 40%). δH (CDCl3) 7.52 (1H, d, J 9.6 Hz), 6.87 (2H, br s), 6.58 (1H, d, J 9.6 Hz), 3.96 (2H, d, J 7.2 Hz), 1.40-1.33 (1H, m), 0.62-0.51 (4H, m). LCMS (ES+) RT 2.92 minutes, 266.0 (M+H)+.

1. temperatureto warm to r.t. over 2 h
2. temperaturethe mixture heated
3. temperatureto reflux for 24 h
4. temperatureThe mixture was cooled
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in acetonitrile (50 ml)
7. temperatureThe mixture was heated to 55° C. for 18 h
8. temperaturethen cooled to r.t.
9. customThe resulting solid was isolated by filtration

ORD record

ord-5cf470669ac949809eafacdad74e49eb

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07795256B2