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X-ray powder diffraction data for 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester, C27H28N4O5

Published online by Cambridge University Press:  13 June 2017

Qing Wang ,
Zi Li Suo ,
Yong Kui Zhang ,
Quan Hou  and
Hui Li
Qing Wang
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Zi Li Suo
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Yong Kui Zhang*
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Quan Hou
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Hui Li*
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
*
a)Author to whom correspondence should be addressed. Electronic mail: zhangyongkui@scu.edu.cn; lihuilab@sina.com
a)Author to whom correspondence should be addressed. Electronic mail: zhangyongkui@scu.edu.cn; lihuilab@sina.com

Abstract

1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7- tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester is an important intermediate in the synthesis of the anticoagulant, apixaban. X-ray powder diffraction data for this compound are reported [a = 14.101(4) Å, b = 10.105(6) Å, c = 9.532(7) Å, α = 72.774(1)°, β = 97.356(3)°, γ = 108.237(3)°, unit-cell volume V = 1231.45 Å3, Z = 2, and space group P-1]. No detectable impurities were observed.

Keywords

pharmaceutical intermediateanticoagulantapixaban

Information

Type
Data Reports
Information
Powder Diffraction , Volume 32 , Issue 3 , September 2017 , pp. 206 - 209
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Copyright
Copyright © International Centre for Diffraction Data 2017 

I INTRODUCTION

Apixaban (Eliquis®) is a novel oral pyrazole-based direct FXa inhibitor; this drug was developed by Bristol-Myers Squibb and Pfizer to treat and prevent thrombotic disorder (Watson et al., Reference Watson, Whiteside and Perry2011). Since May 2011, apixaban has been approved for venous thrombus embolism prevention in adult elective hip or knee replacement patients in various countries, such as the USA, China, Brazil, Australia, New Zealand and some European countries (Deeks, Reference Deeks2012). The title compound (Figure 1) is an important intermediate in the synthesis of the anticoagulant, Apixaban. We have reported the crystal structures of other intermediates in our previous work (Wang et al., Reference Wang, Huang, Sun, Ma and Li2015a, Reference Wang, Xiong, He, Tang and Li2015b, Reference Wang, Xiao, He and Li2015c, Reference Wang, Tang, Tang, He and Li2015d, Reference Wang, Li, Li, Tang and Li2015e, Reference Wang, Guo, Tang and Li2016a, Reference Wang, Zeng, Li and Li2016b). Crystallographic data for some intermediates were deposited with the Cambridge Crystallographic Data Center (CCDC) with a supplementary publication number of CCDC-1504960, 148511, 1504963, 1505268, 1505270. Presently, the crystal structure of the title compound has not been reported.

Figure 1.

Synthesis of the title compound.

II. EXPERIMENTAL

A. Sample preparation

The title compound was prepared according to the literatures (Anon, 2013; Singh et al., Reference Singh, Srivastava, Tripathi, Verma, Vir, Kumar, Masand, Shekhawat, Tiwari and Biswas2015; Ye and Wang, Reference Ye and Wang2015). The melting point and measured density of the title compound are 177-178 °C and 1.33 g cm−3, respectively. The title compound was recrystallized in ethyl acetate and dried. The sample was then ground into powder and mounted on a flat zero background plate.

B. Diffraction data collection and reduction

X-ray powder diffraction (XRD) measurement was performed at room temperature using an X'Pert PRO diffractometer (PANalytical Co., Ltd., Netherlands) with a PIXcel 1D detector and CuKα radiation (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 0.013 13°2θ and a counting time of 50 ms step−1. Figure 2 shows the powder X-ray diffraction pattern of the title compound.

Figure 2.

X-ray powder diffraction (XRD) pattern of the title compound using CuK α radiation.

The software package Material Studio 8.0 (Accelrys Co., Ltd., CA, USA) was used to process the data in the Analytical & Testing Center (Sichuan University, Chengdu, China). The XRD pattern was pre-treated by subtracting the background, smoothing, and stripping off the Kα 2 component. Automatic indexing results were obtained by X-Cell method (Neumann, Reference Neumann2003). The preliminary cell from indexing was refined using the Pawley method (Pawley, Reference Pawley1981), which involves assigning the Miller indices (h, k, l) to each observed peak in the experimental powder XRD pattern.

III. RESULTS

Based on the characteristic peaks, the detected form of the title compound in the present study could be classified as Form A (Anon, 2013). Pawley refinement results confirmed that the title compound is triclinic with space group P-1 and unit-cell parameters: a = 14.101(4)  Å, b = 10.105(6)  Å, c = 9.532(7) Å, α = 72.774(1)°, β = 97.356(3)°, γ = 108.237(3)°, unit-cell volume V = 1231.45 Å3, Z = 2 and ρ x  = 1.318 g cm−3. The values of 2θ obs, d obs, I obs, h, k, l, 2θ cal, d cal, Δ2θ are listed in Table I.

Table I.

Indexed X-ray powder diffraction data for the title compound. The d-values were calculated using CuKα 1 radiation (λ = 1.540 56 Å).

SUPPLEMENTARY MATERIAL

The supplementary material for this article can be found at https://doi.org/10.1017/S0885715617000574

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).

References

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Figure 0

Figure 1. Synthesis of the title compound.

Figure 1

Figure 2. X-ray powder diffraction (XRD) pattern of the title compound using CuKα radiation.

Figure 2

Table I. Indexed X-ray powder diffraction data for the title compound. The d-values were calculated using CuKα1 radiation (λ = 1.540 56 Å).

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