Dabigatran etexilate is a novel synthetic direct thrombin inhibitor, a prodrug of dabigatran, a non-peptide thrombin inhibitor. Dabigatran etexilate intermediate II is an impurity produced during the preparation of dabigatran etexilate.
N-(4-Cyanophenyl)glycine is a off-white Solid.
N-(4-Cyanophenyl)-glycine (cas# 42288-26-6) is a compound useful in organic synthesis.
Dabigatran etexilate intermediate
3.2.3 Preparation of [(4-cyanophenyl)amino]acetic acid (V). Molecular formula: C9H8N2O2. molecular weight: 176.17. Raw materials: 90g (0.75mol) of bromoacetic acid (F), 211.7g (1.5mol) of p-aminobenzonitrile (G), 35g (0.42mol) of sodium bicarbonate. Procedure: bromoacetic acid (F) and p-aminobenzonitrile (G) were mixed in 1250 ml of water to form a suspension. The suspension was placed in a bath heated to 100-110°C for 3 hours. Upon completion of the reaction, the reaction vessel was removed from the bath and cooled to room temperature, followed by further cooling in a refrigerator. The precipitate was separated by diafiltration and dried in a vacuum desiccator at 100 °C. Yield of crude product: 122 g (92.8% yield), HPLC purity: 97%. Purification step: the crude product was converted to sodium salt and re-acidified using aqueous sodium bicarbonate to release the free acid by dilute hydrochloric acid (1:1). After filtration, the product was washed with water and dried in a vacuum desiccator at 105°C. The product was then purified to a sodium salt using aqueous sodium bicarbonate. Yield of purified product: 115 g (88% yield), HPLC purity: 99.1%, water content: 0.13%, sulfated ash: 1.8%.
[1] Patent: WO2009/111997, 2009, A1. Location in patent: Page/Page column 11
[2] Patent: WO2013/111163, 2013, A2. Location in patent: Page/Page column 18
[3] Patent: US2015/11589, 2015, A1. Location in patent: Paragraph 0121-0122
[4] European Journal of Medicinal Chemistry, 2016, vol. 120, p. 148 - 159
