{
  "abstract": "Clonidine•HCl is a clinically important imidazoline derivative whose manufacturing routes have seen little innovation since their development in the mid-to-late 20th century. Its widespread use as an antihypertensive and neuroactive agent underscores the need for more efficient, modern production strategies. Herein, we report the first continuous flow strategy for the synthesis of clonidine. By integrating telescoped multistep sequences, inline liquid-liquid workup, advanced solid handling, and machine learning, we developed an intensified process that delivers clonidine•HCl in only 24 min total residence time across 5 continuous transformations, achieving an overall yield of 54%. This approach significantly outperforms conventional batch protocols, which typically require more than 18 h. The platform enables efficient and precisely controlled isothiocyanate formation, thiourea hydrolysis, S-methylation, and imidazoline cyclisation, while reducing intermediate isolations, minimising reagent handling, and eliminating hazardous materials associated with legacy routes. These advances provide a scalable, data-driven manufacturing solution and establish a foundation for intensified production of clonidine and related APIs under continuous flow conditions.",
  "abstract_shown": true,
  "affiliations": [
    "Pharmaceutical Technologies, Council for Scientific and Industrial Research (CSIR)",
    "ReactWise Technologies Ltd",
    "Institute of Chemistry for Life and Health Sciences, Chimie ParisTech, CNRS, PSL Research University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cloudius R. Sagandira"
    },
    {
      "affs": [
        0
      ],
      "name": "Sinazo Nqeketo"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexander Pomberger"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel Wigh"
    },
    {
      "affs": [
        2
      ],
      "name": "Christophe Len"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1aq7cdz1m04rk.bib",
  "cited_by": 0,
  "doi": "10.1038/s42004-026-02096-2",
  "fulltext_url": "https://doi.org/10.1038/s42004-026-02096-2",
  "id": "1aq7cdz1m04rk",
  "issns": [
    "2399-3669"
  ],
  "landing_url": "https://doi.org/10.1038/s42004-026-02096-2",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QD1-999"
    ],
    [
      "openalex",
      "2204|Innovative Microfluidic and Catalytic Techniques Innovation"
    ]
  ],
  "openalex": "W7166577715",
  "pdf_url": "https://www.nature.com/articles/s42004-026-02096-2_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/1aq7cdz1m04rk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:48Z",
      "native_id": "bb9ea86571e146a89a180c412c9d4c82",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s42004-026-02096-2"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "lcc:QD1-999",
      "subfield": "general"
    }
  ],
  "title": "Machine-learning-assisted continuous flow synthesis of clonidine",
  "title_text": "Machine-learning-assisted continuous flow synthesis of clonidine",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:48Z",
  "url": "https://research.draconitic.com/paper/1aq7cdz1m04rk",
  "venue": "Communications Chemistry",
  "versions": []
}