Uses
(S)-1-(3,5-Dichloropyridin-4-yl)ethanol is used to prepare (R)-(E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol useful in the treatment of cancer.
Synthesis
General procedure for the synthesis of (S)-1-(3,5-dichloropyridin-4-yl)ethanol from 1-(3,5-dichloropyridin-4-yl)ethanol: Firstly, chiral separation of the mixture of stereoisomers was carried out by a CHIRALPAK AD-H column with 90% heptane/10% ethanol as eluent. The second elution peak, the target enantiomer (S)-1-(3,5-dichloropyridin-4-yl)ethanol, was collected. To determine the absolute configuration of the product, the sample was dissolved in CDCl3 (final concentration 100 mg/mL) and vibrational circular dichroism (VCD) and infrared (IR) spectra were acquired using a ChiralIR FT VCD spectrometer equipped with a BaF2 window and a 100-mm path-length IR unit (BioTools Inc.), with a resolution of 4 cm-1 . using a 150 μL of sample and an acquisition time of 6 h. The data were collected using a VCD spectrometer (BioTools Inc.). Data were presented directly without smoothing or other post-processing. The lowest energy conformation was optimized at the B3PW91/6-31G** level of theory by Gaussian software on a Linux cluster, vibrational frequencies, absorption intensities and VCD intensities were calculated, and vibrational circular dichroism spectra were simulated with a 6 cm-1 Lorentz bandwidth. The analytical results confirm that the product is in S-configuration. Yield: 84.37 g (27% yield). Mass spectrum (electrospray ionization) m/z 192 [M-H]+.
References
[1] Patent: WO2010/129509, 2010, A1. Location in patent: Page/Page column 4
[2] Patent: US2012/83511, 2012, A1. Location in patent: Page/Page column 2
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 14, p. 6690 - 6708
[4] Patent: CN103819396, 2016, B
