Download PDF
Synthesis 2023; 55(13): 2061-2069
DOI: 10.1055/a-2016-4337
paper

New, Scalable Process for the Preparation of 5-Acetyl-1H-pyrazole-3-carboxylic Acid, a Key Intermediate of Darolutamide

László Poszávácz
,
Tamás Nagy
,
Katalin Kátai-Fadgyas
,
Balázs Volk  ∗
› Further Information
    Permissions and Reprints All articles of this category


Dedicated to the memory of late Professor Ferenc Fülöp (1952–2021)

Abstract

A new, efficient process for the synthesis of 5-acetyl-1H-pyrazole-3-carboxylic acid, a versatile building block and the key intermediate of darolutamide, using diethyl pyrazole-3,5-dicarboxylate as the starting material is described. Contrary to the synthetic routes known from the literature, this procedure does not employ explosive diazo reagents, moreover it is simple and safe, thereby suitable for scale-up.

Keywords

ester hydrolysis - regioselectivity - drug substance - key intermediate - safety - scalability

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2016-4337.
  • Supporting Information


Publication History

Received: 03 January 2023

Accepted after revision: 19 January 2023

Accepted Manuscript online:
19 January 2023

Article published online:
14 March 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Moilanen A.-M, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ. Sci. Rep. 2015; 5: 12007
    CrossrefPubMed
  • 2 Fizazi K, Albiges L, Loriot Y, Massard C. Expert Rev. Anticancer Ther. 2015; 15: 1007
    CrossrefPubMed
  • 3 Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR. N. Eng. J. Med. 2019; 380: 1235
    CrossrefPubMed
  • 4 Sugawara T, Baumgart SJ, Nevedomskaya E, Reichert K, Steuber H, Lejeune P, Mumberg D, Haendler B. Int. J. Cancer 2019; 145: 1382
    CrossrefPubMed
  • 5 U.S. Food and Drug Administration (FDA) approves darolutamide, 31 July 2019 (accessed February 20, 2023): https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-non-metastatic-castration-resistant-prostate-cancer.
  • 6 Matsubara N, Mukai H, Hosono A, Onomura M, Sasaki M, Yajima Y, Hashizume K, Yasuda M, Uemura M, Zurth C. Cancer Chemother. Pharmacol. 2017; 80: 1063
    CrossrefPubMed
  • 7 Wohlfahrt G, Törmäkangas O, Salo H, Hölung L, Karjalainen A, Knuuttila P, Holm P, Rasku S, Vesalainen A. PCT Intern. Pat. Appl. WO 2011051540, 2011 ; Chem. Abstr. 2011, 154, 540477.
    PubMed
  • 8 U.S. Food and Drug Administration (FDA), 9 August 2019 (accessed February 20, 2023): https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-nubeqa
  • 9 FDA Approved Drug Products: NUBEQA (darolutamide) tablets, for oral use 2019 (accessed February 20, 2023): https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/ 212099Orig1s000lbl.pdf
  • 10 Törmäkangas O, Heikkinen T. PCT Intern. Pat. Appl. WO 2016120530, 2016 ; Chem. Abstr. 2016, 165, 247292.
    PubMed
  • 11 Törmäkangas O, Wohlfahrt G, Salo H, Ramasubramanian RD, Patra PK, Martin AE, Heikkinen T, Vesalain A, Moilanen A, Karjalainen A. PCT Intern. Pat. Appl. WO 2012143599, 2012 ; Chem. Abstr. 2012, 157, 634352.
    PubMed
  • 12 Laitinen I, Karjalainen O. PCT Intern. Pat. Appl. WO 2016162604, 2016 ; Chem. Abstr. 2016, 165, 487647.
    PubMed
  • 13 Yu J, Zhou P, Hu M, Yang L, Yan G, Xu R, Deng Y, Li X, Chen Y. Eur. J. Med. Chem. 2019; 182: 111608
    CrossrefPubMed
  • 14 Semple G, Averbuj C, Skinner P, Gharbaoui T, Shin Y.-J. PCT Intern. Pat. Appl. WO 2004032928, 2004 ; Chem. Abstr. 2004, 140, 357332.
    PubMed
  • 15 Casuscelli F, Brasca MG, Caldarelli M, Cervi G, Disingrini T, Quartieri F. PCT Intern. Pat. Appl. WO 2012139930, 2012 ; Chem. Abstr. 2012, 157, 634390.
    PubMed
  • 16 Lai KW, Liang J, Zhang B, Labadie S, Ortwine D, Gehling VS, Harmange J.-C. PCT Intern. Pat. Appl. WO 2016057924, 2016 ; Chem. Abstr. 2016, 164, 507513.
    PubMed
  • 17 Fang J, Li Y, Guo W, Wu Y. Chinese Pat. Appl. CN 111138289, 2020 ; Chem. Abstr. 2020, 173, 293895.
    PubMed
  • 18 Nan J, Chao-Jun L. Chem. Commun. 2004; 394
    PubMed
  • 19 Liu C, Weng Y, Zeng X, Zeng W, Wang X, Hu Y. Tetrahedron Lett. 2019; 60: 493
    Crossref
  • 20 Cvetovich RJ, Pipik B, Hartner FW, Grabowski EJ. J. Tetrahedron Lett. 2003; 44: 5867
    Crossref
  • 21 Barge M, Kamble S, Kumbhar A, Rasinkar G, Salunkhe R. Monatsh. Chem. 2013; 144: 1213
    Crossref
  • 22 Kidwai M, Jain A, Poddar R. J. Organomet. Chem. 2011; 696: 1939
    Crossref
  • 23 Fu P, Li Z, Wang Y, Yu P. Asian J. Chem. 2015; 27: 2545
    Crossref
  • 24 Hartner FW, Cvetovich RJ, Tsay F.-R, Amato JS, Pipik B, Grabowski EJ. J, Reider PJ. J. Org. Chem. 1999; 64: 7751
    Crossref
  • 25 Wiles Ch, Watts P, Haswell SJ. Org. Process Res. Dev. 2004; 8: 28
    Crossref
  • 26 Nesmejanow AN, Kotschetkow NK. Izv. Akad. Nauk SSSR, Ser. Khim. 1951; 686 ; Chem. Abstr. 1952, 46, 7565