Use of Immobilized Amine Transaminase from Vibrio fluvialis under Flow Conditions for the Synthesis of (S)‐1‐(5‐Fluoropyrimidin‐2‐yl)‐ethanamine

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6 Jan, 2020

We report on the covalent immobilization of the (S)‐selective amine transaminase from Vibrio fluvialis (Vf‐ATA) and its use in the synthesis of (S)‐1‐(5‐fluoropyrimidin‐2‐yl)‐ethanamine, a key intermediate of the JAK2 kinase inhibitor AZD1480. Immobilized Vf‐ATA on glyoxyl‐agarose (activity recovery: 30%) was used in a packed bed reactor to set‐up a continuous flow biotransformation coupled with a straightforward in‐line purification to circumvent the 2‐step process described in literature for the batch reaction. The newly developed biotransformation was run in a homogeneous system including dimethyl carbonate as a green co‐solvent. Optically pure (S)‐1‐(5‐fluoropyrimidin‐2‐yl)‐ethanamine (ee >99%) was isolated in 35% yield.

  • Riccardo Semproli [a]
  • Gianmarco Vaccaro [a],[b]
  • Erica E. Ferrandi [c]
  • Marta Vanoni [c]
  • Teodora Bavaro [a]
  • Giorgio Marrubini [a]
  • Francesca Annunziata [b]
  • Paola Conti [b]
  • Giovanna Speranza [d]
  • Daniela Monti [*c]
  • Lucia Tamborini [*b]
  • Daniela Ubiali [*a]
  • [a] R. Semproli, G. Vaccaro, Dr. G. Marrubini, Dr. T. Bavaro, Prof. D. Ubiali, Department of Drug Sciences, University of Pavia, Viale Taramelli 12, I-27100 Pavia, Italy
  • [b] G. Vaccaro, F. Annunziata, Prof. P. Conti, Prof. L. Tamborini, Department of Pharmaceutical Sciences, University of Milano, Via Mangiagalli 25, I-20133 Milano, Italy
  • [c] Dr. E. E. Ferrandi, M. Vanoni, Dr. D. Monti, Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC) – CNR, Via Bianco 9, I-20131 Milano, Italy
  • [d] Prof. G. Speranza, Department of Chemistry, University of Milano, Via Golgi 19, I-20133 Milano, Italy
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