Inductive electrospray ionization (iESI) is an ambient ionization method that is particularly well-suited to online reaction monitoring. It allows the potential of electrospray mass spectrometry (MS) to be realized as a routine process analytical technology (PAT) tool to monitor practical synthetic reactions in real time. In this study, a synthetic route to Anagliptin (target API) was successfully monitored using online iESI-MS. Starting materials not seen by traditional reaction monitoring tools (HPLC-UV/Vis and GC-FID) were observed, as well as water-sensitive reagents and intermediates which cannot easily be followed by other methods. Online tandem mass spectrometry (MS/MS) was used to characterize chemical species in the reaction mixture. Impurities and byproducts were identified, and information on the progress of byproduct formation enabled implementation of strategies to eliminate these byproducts in the course of the reaction. This work demonstrates how iESI-MS can be employed to obtain comprehensive information and solutions to some practical problems that occur in small-molecule synthetic reaction monitoring.

Online Inductive Electrospray Ionization Mass Spectrometry as a Process Analytical Technology Tool To Monitor the Synthetic Route to Anagliptin

Xin Yan†, Ryan M. Bain†, Yafeng Li†, Ran Qiu†, Tawnya G. Flick*‡, and R. Graham Cooks*†

† Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States

‡ Department of Analytical Research & Development, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California 91320, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00039

Publication Date (Web): April 12, 2016

Copyright © 2016 American Chemical Society

*E-mail for T.G.F.: tflick@amgen.com., *E-mail for R.G.C.: cooks@purdue.edu.

http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00039

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Yazd, Iran

Yazd
City in Iran
Yazd is the capital of Yazd Province, Iran. The city is located 270 km southeast of Esfahan. At the 2011 census, the population was 1,074,428 in 270٬575 families. Wikipedia
Weather: 26°C, Wind N at 8 km

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ANAGLIPTIN

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
CAS No.:	739366-20-2
Synonyms:	Anagliptin;
Formula:	C19H25N7O2
Exact Mass:	383.20700

Anagliptin chemically known as N-[2-[2-[2(S)-cyanopyrrolidin-l-yl]-2-oxoethylamino]- 2-methylpropyl]-2-methylpyrazolo[l,5-a]pyrimidine-6-carboxamide is represented by the structural formula:

Anagliptin is a dipeptidyl peptidase IV- inhibitor. United States Patent No 7345 1 80- (IJS' 180) discloses anagliptin.     Example 5: Synthesis of N-[2-2[2(S)-Cyano pyrrolidin-l-yl]-2-oxoethyIamino]-2- methyIpropyl]-2-methyaIpyrazoIo [1, 5-a] pyrimidine-6-carboxamide (I, anagliptin). 1H NMR (300 MHz, CDC1₃): δ 1.16 (s, 6H), 2.23(m, 4H), 2.54(s, 3H), 3.25-3.51 (m, 6H), 4.78 (m, 1H), 6.53 (s, 1H), 8.05 (s, 1H), 8.93 (s, 1H), 9.22(s, 1H) HPLC Purity: 99.71%, Chiral purity: 100%

.........WO2014147640A2




 Kato, M.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M.; Mirensha, Y.; Kakigami, T. Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]- 2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg. Med. Chem. 2011, 19, 7221–7227. http://www.sciencedirect.com/science/article/pii/S0968089611007784


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