3-(2-chloropyriMidin-4-yl)-1H-indole

Uses

2,3,4-Trimethoxybenzaldehyde is an important pharmaceutical intermediate used in the synthesis of novel Ca2+ channel blockers. This drug can selectively target cerebral arteries to reduce the incidence of headaches and has a certain market demand in Europe and the United States. It can also be used as impurity C in trimetazidine, contributing to the standardization process during trimetazidine development. Impurity research is a crucial aspect of drug development.

Application

3-(2-Chloro-pyrimidin-4-yl)-1H-indole can be used as an organic synthesis intermediate and a pharmaceutical intermediate, mainly in laboratory research and development processes and chemical and pharmaceutical synthesis processes.

Synthesis

General procedure for the synthesis of 3-(2-chloropyrimidin-4-yl)-1H-indole from indole and 2,4-dichloropyrimidine: 3-(2-chloropyrimidin-4-yl)-1H-indole (1 g, 4.37 mmol), 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (810 mg, 4.37 mmol), and p-toluenesulfonic acid (750 mg, 4.37 mmol) were dissolved in 2-pentanol (40 mL). The reaction mixture was heated and stirred at 110 °C for 3 hours. The progress of the reaction was monitored by LCMS and after confirming the completion of the reaction, the reaction mixture was naturally cooled to room temperature and a dark colored solid was precipitated. The solid was collected by filtration and the filter cake was washed sequentially with methanol and methyl tert-butyl ether to give 3-(2-chloropyrimidin-4-yl)-1H-indole (1.3 g, 79% yield).

References

[1] Patent: EP3205650, 2017, A1. Location in patent: Paragraph 0106; 0512; 0513
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 7025 - 7048
[3] Patent: CN105153122, 2018, B. Location in patent: Paragraph 0034; 0117; 0118; 0119; 0120
[4] Patent: WO2013/14448, 2013, A1. Location in patent: Page/Page column 139
[5] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267