1-[3-(Benzoyloxy)propyl]-2,3-dihydro-5-(2-nitropropyl)-1H-indole-7-carbonitrile

Uses

3-(7-Cyano-5-(2-nitropropyl)indolin-1-yl)propyl Benzoate is used in the preparation of Silodosin (S465000), an α1a-adrenoceptor antagonist. It is used in treatment of benign prostatic hypertophy.

Synthesis

1-[3-(Benzoyloxy)propyl]-2,3-dihydro-5-(2-nitropropyl)-1H-indole-7-carboxaldehyde (20.0 g) was used as a starting material and dissolved in tetrahydrofuran (29.0 ml). To this solution, hydroxylamine hydrochloride (4.21 g) and pyridine (16.0 ml) were added sequentially. The reaction mixture was stirred at a constant temperature at 50 °C for 2 h. Acetic anhydride (9.0 ml) was subsequently added. Stirring of the reaction mixture was continued at 80°C for 2 hours. After completion of the reaction, extraction was carried out with toluene. The toluene layer obtained by extraction was washed with dilute hydrochloric acid, after which the solvent was removed by distillation under reduced pressure to give 16.0 g of propyl 3-(7-cyano-5-(2-nitropropyl)dihydroindol-1-yl)benzoate (Compound XX).

References

[1] Patent: WO2011/124704, 2011, A1. Location in patent: Page/Page column 19-20
[2] Patent: WO2013/56842, 2013, A1. Location in patent: Page/Page column 19
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 8, p. 3826 - 3839