{
  "abstract": "The use of thiophenols on process scales is fraught with challenges relating to their toxicity, malodor, and air sensitivity. We previously demonstrated that the Ni-catalyzed C–S coupling of aryl iodides and thiourea provides a discovery-scale route to S-aryl isothiouronium salts, which serve as bench stable, odorless, and highly crystalline surrogates of thiophenols. Here, we report the process optimization of this methodology for the synthesis of a key intermediate to kinase inhibitor tozasertib (VX-680). The corollary is a reduction in catalyst loading to 0.5 mol %, elimination of NMP solvent, and introduction of a direct crystallization, giving 95% yield on a 100 g scale.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Richard Herzog"
    },
    {
      "name": "Olivia L Munns"
    },
    {
      "name": "Valentin Magné"
    },
    {
      "name": "Stephen P Argent"
    },
    {
      "name": "Liam T Ball"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/enfezdz9t7jkq.bib",
  "cited_by": 1,
  "doi": "10.1021/acs.oprd.6c00143",
  "fulltext_url": null,
  "id": "enfezdz9t7jkq",
  "issns": [
    "1083-6160",
    "1520-586X"
  ],
  "landing_url": "https://hal.science/hal-05760747v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.chim"
    ],
    [
      "hal",
      "1.chim.cata"
    ],
    [
      "hal",
      "1.chim.geni"
    ],
    [
      "openalex",
      "1605|Sulfur-Based Synthesis Techniques"
    ]
  ],
  "openalex": "W7196967362",
  "pdf_url": "https://hal.science/hal-05760747/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-06",
  "publisher": "American Chemical Society",
  "ris": "https://research.draconitic.com/paper/enfezdz9t7jkq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "hal-05760747",
      "source": "hal",
      "url": "https://hal.science/hal-05760747v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "hal:1.chim.cata",
      "subfield": "catalysis"
    }
  ],
  "title": "Scalable Synthesis of a Masked Thiophenol as an Air-Stable, Odorless Intermediate to the Aurora Kinase Inhibitor Tozasertib (VX-680)",
  "title_text": "Scalable Synthesis of a Masked Thiophenol as an Air-Stable, Odorless Intermediate to the Aurora Kinase Inhibitor Tozasertib (VX-680)",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/enfezdz9t7jkq",
  "venue": "Organic Process Research and Development",
  "versions": []
}