I. INTRODUCTION
Palbociclib [PD-0332991, chemical name 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one] (Figure 1) developed as IBRANCE by Pfizer, is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival by FDA on February 2015.
The structure of Palbociclib.
Presently, the crystal structure of Palbocilib has not been reported.
II. EXPERIMENTAL
A. Sample preparation
The title compound was purchased from Sichuan CheCO Pharmaceutical Technology Co., Ltd, China. It was re-crystallized in acetone and water, and then dried and ground into powder. The structure of Palbociclib was characterized by high-performance liquid chromatography (HPLC), high-resolution mass spectrum (HRMS), Fourier transform infrared spectroscopy, and 1H-NMR.
The purity of sample is 99.5% measured by HPLC, HRMS showed m/z = 448.2417 peak, the melting point is 269–271 °C, the infrared spectrum is consistent with the structure, 1H-NMR (see supporting information) is consistent with literature (Chekal and Ide, Reference Chekal and Ide2014).
B. X-ray powder diffraction (XRPD) data collection and reduction
The diffraction pattern for the title compound was collected at room temperature using an X'Pert PRO diffractometer (PANalytical Co., Ltd, The Netherlands) with an X'celerator detector and CuKα 1 radiation (λ = 1.54056 Å, generator setting: 40 kV and 40 mA). The diffraction data were collected over the angular range from 4 to 50° 2θ with a step size of 0.01313° 2θ and a counting time of 30 ms step−1. Data evaluation was performed using the software package Material Studio 4.2 (Accelrys Co., Ltd, USA).
The powder diffraction pattern was pretreated by subtracting the background and smoothing. Through analyzing the peak positions in the XRPD pattern by the X-Cell method from “Powder Indexing”, the preliminary unit-cell parameters were obtained. The indexing results were then refined using the Pawley refinement (Pan et al., Reference Pan, Guo, Duan, Cheng and Li2012), which involves assigning the Miller indices (h, k, l) to each observed peak in the experimental powder XRD pattern (Harris, Reference Harris2012). After Pawley refinement, the final R wp of the spectrogram was converged to 6.95%.
III. RESULTS
The experimental powder diffraction pattern is depicted in Figure 2. Pawley refinement confirms that the lattice type of Palbociclib is triclinic with space group P-1 and unit-cell parameters: [a = 18.182(2) Å, b = 11.508(1) Å, c =5.041(1) Å, α = 81.282(7)°, β = 97.423(7)°, γ = 102.415(2)°, unit-cell volume V = 1013.1(4) Å3, Z = 2]. The values of 2θ obs, d obs, I obs, h, k, l, 2θ cal, d cal, and Δ2θ are listed in Table I.
XRPD pattern of Palbocilib.
Indexed XRPD data of Palbociclib, C24H29N7O2
Only the peaks with I rel of 2 or greater are reported a = 18.182(2) Å, b = 11.508(1) Å, c = 5.041(1) Å, α = 81.282(7)°, β = 97.423(7)°, γ = 102.415(2)°, unit-cell volume V = 1013.1(4) Å3, Z = 2, and space group P-1. All measured lines were indexed. The d-values were calculated using CuK α1 radiation (λ = 1.54056 Å).
SUPPLEMENTARY MATERIAL
The supplementary material for this article can be found at http://dx.doi.org/10.1017/S0885715616000233.
ACKNOWLEDGEMENTS
This work was supported by the Applied Basic Research Project of Sichuan Province (Grant no. 2014JY0042) and the National Development and Reform Commission and Education of China (Grant no. 2014BW011).
