Abstract
Flow chemistry has become a vibrant area for research over the past decade. This perspective is intended to capture insights on how these advances have and will continue to impact the development and commercialization of active pharmaceutical ingredients. A series of chemistry examples from a number of pharmaceutical companies will highlight the influence of flow chemistry on this industry.
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Plutschack, M. B.; Pieber, B.; Gilmore, K.; Seeberger, P. H. Chem. Rev. 2017, 117, 11796–11893.
Gutmann, B.; Kappe, C. O. J. Flow Chem. [Ahead-of-print] DOI: 10.1556/1846.2017.00009. Published online: Aug 9, 2017.
Haber, F.; Le Rossignol, R. Z. Elektrochem. Angew. Phys. Chem. 1913, 19, 53.
https://energy.gov/eere/fuelcells/hydrogen-production-natural-gas-reforming (accessed October 6, 2017).
Franke, R.; Selent, D.; Börner, A. Chem. Rev. 2012, 112, 5675–5732.
https://www.fda.gov/downloads/drugs/guidances/ucm261078.pdf (accessed October 6, 2017).
Bray, B. L. Nat. Rev. Drug Discovery 2003, 2, 587–593.
https://www.fda.gov/ohrms/dockets/98fr/fda-2008-d-0629-gdl.pdf (accessed October 6, 2017).
https://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050796.htm#q4 (accessed October 6, 2017).
https://www.lilly.com/pipeline/.
http://pqri.org/wp-content/uploads/2017/02/1-Lee-PQRI-for-CM-2017.pdf (accessed October 6, 2017).
Almaya, A.; De Belder, L.; Meyer, R.; Nagapudi, K.; Lin, H.-R. H.; Leavesley, I.; Jayanth, J.; Bajwa, G.; DiNunzio, J.; Tantuccio, A.; Blackwood, D.; Abebe, A. J. Pharm. Sci. 2017, 106, 930–943.
Cole, K. P.; Groh, J. M.; Johnson, M. D.; Burcham, C. L.; Campbell, B. M.; Diseroad, W. D.; Heller, M. R.; Howell, J. R.; Kallman, N. J.; Koenig, T. M.; May, S. A.; Miller, R. D.; Mitchell, D.; Myers, D. P.; Myers, S. S.; Phillips, J. L.; Polster, C. S.; White, T. D.; Cashman, J.; Hurley, D.; Moylan, R.; Sheehan, P.; Spencer, R. D.; Desmond, K.; Desmond, P.; Gowran, O. Science 2017, 356, 1144–1150.
https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf (accessed October 6, 2017).
Lee, S. L.; O’Connor, T. F.; Yang, X.; Cruz, C. N.; Chatterjee, S.; Madurawe, R. D.; Moore, C. M. V.; Yu, L. X.; Woodcock, J. J. Pharm. Innov. 2015, 10, 191–199.
Mascia, S.; Heider, P. L.; Zhang, H.; Lakerveld, R.; Benyahia, B.; Barton, P. I.; Braatz, R. D.; Cooney, C. L.; Evans, J. M. B.; Jamison, T. F.; Jensen, K. F.; Myerson, A. S.; Trout, B. L. Angew Chem., Int Ed. 2013, 52, 12359–12363.
Adamo, A.; Beingessner, R. L.; Behnam, M.; Chen, J.; Jamison, T. F.; Jensen, K. F.; Monbaliu, J.-C. M.; Myerson, A. S.; Revalor, E. M.; Snead, D. R.; Stelzer, T.; Weeranoppanant, N.; Wong, S. Y.; Zhang, P. Science 2016, 352, 61–67.
Nettekoven, M.; Püllmann, B.; Martin, R. E.; Wechsler, D. Tetrahedron Lett. 2012, 53, 1363–1366.
Petersen, T. P.; Mirsharghi, S.; Rummel, P. C.; Thiele, S.; Rosenkilde, M. M.; Ritzén, A.; Ulven, T. Chem. — Eur J. 2013, 19, 9343–9350.
Lehmann, J.; Alzieu, T.; Martin, R. E.; Britton, R. Org. Lett. 2013, 15, 3550–3553.
Martin, R. E.; Lehmann, J.; Alzieu, T.; Lenz, M.; Carnero Corrales, M. A.; Aebi, J. D.; Peter Märki, H.; Kuhn, B.; Amrein, K.; Maywega, A. V.; Britton, R. Org. Biomol. Chem. 2016, 14, 5922–5927.
Werner, M.; Kuratli, C.; Martin, R. E.; Hochstrasser, R.; Wechsler, D.; Enderle, T.; Alanine, A. I.; Vogel, H. Angew Chem., Int. Ed. 2014, 53, 17041708.
Baranczak, A.; Tu, N. P.; Marjanovic, J.; Searle, P. A.; Vasudevan, A.; Djuric, S. W. ACS Med. Chem. Lett. 2017, 8, 461–465.
Sutherland, J. D.; Tu, N. P.; Nemcek, T. A.; Searle, P. A.; Hochlowski, J. E.; Djuric, S. W.; Pan, J. Y. J. Lab. Autom. 2014, 19, 176–182.
Tu, N. P.; Hochlowski, J. E.; Djuric, S. W. Mol. Diversity 2012, 16, 53–58.
Hwang, Y.-J.; Coley, C. W.; Abolhasani, M.; Marzinzik, A. L.; Koch, G.; Spanka, C.; Lehmann, H.; Jensen, K. F. Chem. Commun. 2017, 53, 6649–6652.
Desai, B.; Dixon, K.; Farrant, E.; Feng, Q.; Gibson, K. R.; van Hoorn, W. P.; Mills, J.; Morgan, T.; Parry, D. M.; Ramjee, M. K.; Selway, C. N.; Tarver, G. J.; Whitlock, G.; Wright, A. G. J. Med. Chem. 2013, 56, 3033–3047.
DeLano, T. J.; Bandarage, U. K.; Palaychuk, N.; Green, J.; Boyd, M. J. J. Org. Chem. 2016, 81, 12525–12531.
Li, H.; Moncecchi, J.; Truppo, M. D. Org. Process Res. Dev 2015, 19, 695–700.
Tsoung, J.; Bogdan, A. R.; Kantor, S.; Wang, Y.; Charaschanya, M.; Djuric, S. W. J. Org. Chem. 2017, 82, 1073–1084.
Baucom, K. D.; Jones, S. C.; Roberts, S. W. Org. Lett. 2016 18, 560–563.
Li, H.; Sheeran, J. W.; Clausen, A. M.; Fang, Y.-Q.; Bio, M. M.; Bader, S. Angew Chem., Int. Ed. 2017, 56, 9425–9429.
Thaisrivongs, D. A.; Naber, J. R.; McMullen, J. P. Org. Process Res. Dev. 2016, 20, 1997–2004.
Chung, J. Y. L.; Shevlin, M.; Klapars, A.; Journet, M. Org. Lett. 2016, 18, 1812–1815.
Gustafsson, T.; Soerensen, H.; Ponten, F. Org. Process Res. Dev. 2012, 16, 925–929.
Usutani, H.; Nihei, T.; Papageorgiou, C. D.; Cork, D. G. Org. Process Res. Dev. 2017, 21, 669–673.
Broom, T.; Hughes, M.; Szczepankiewicz, B. G.; Ace, K.; Hagger, B.; Lacking, G.; Chima, R.; Marchbank, G.; Alford, G.; Evans, P.; Cunningham, C.; Roberts, J. C.; Perni, R. B.; Berry, M.; Rutter, A.; Watson, S. A. Org. Process Res. Dev. 2014, 18, 1354–1359.
Braden, T. M.; Johnson, M. D.; Kopach, M. E.; McClary Groh, J.; Spencer, R. D.; Lewis, J.; Heller, M. R.; Schafer, J. P.; Adler, J. J. Org. Process Res. Dev. 2017.
Tsukanov, S. V.; Johnson, M. D.; May, S. A.; Rosemeyer, M.; Watkins, M. A.; Kolis, S. P.; Yates, M. H.; Johnston, J. N. Org. Process Res. Dev. 2016, 20, 215–226.
Li, B.; Widlicka, D.; Boucher, S.; Hayward, C.; Lucas, J.; Murray, J. C.; O’Neil, B. T.; Pfisterer, D.; Samp, L.; VanAlsten, J.; Xiang, Y.; Young, J. Org. Process Res. Dev. 2012, 16, 2031–2035.
May, S. A.; Johnson, M. D.; Buser, J. Y.; Campbell, A. N.; Frank, S. A.; Haeberle, B. D.; Hoffman, P. C.; Lambertus, G. R.; McFarland, A. D.; Moher, E. D.; White, T. D.; Hurley, D. D.; Corrigan, A. P.; Gowran, O.; Kerrigan, N. G.; Kissane, M. G.; Lynch, R. R.; Sheehan, P.; Spencer, R. D.; Pulley, S. R.; Stout, J. R. Org. Process Res. Dev. 2016, 20, 1870–1898.
Johnson, M. D.; May, S. A.; Haeberle, B.; Lambertus, G. R.; Pulley, S. R.; Stout, J. R. Org. Process Res. Dev. 2016, 20, 1305–1320.
Osterberg, P. M.; Niemeier, J. K.; Welch, C. J.; Hawkins, J. M.; Martinelli, J. R.; Johnson, T. E.; Root, T. W.; Stahl, S. S. Org. Process Res. Dev. 2015, 19, 1537–1543.
Abrams, M. L.; Buser, J. Y.; Calvin, J. R.; Johnson, M. D.; Jones, B. R.; Lambertus, G.; Landis, C. R.; Martinelli, J. R.; May, S. A.; McFarland, A. D.; Stout, J. R. Org. Process Res. Dev. 2016, 20, 901–910.
White, T. D.; Berglund, K. D.; Groh, J. M.; Johnson, M. D.; Miller, R. D.; Yates, M. H. Org. Process Res. Dev. 2012, 16, 939–957.
Rydzak, J. W.; White, D. E.; Airiau, C. Y.; Sterbenz, J. T.; York, B. D.; Clancy, D. J.; Dai, Q. Org. Process Res. Dev. 2015, 19, 203–214.
May, S. A.; Johnson, M. D.; Braden, T. M.; Calvin, J. R.; Haeberle, B. D.; Jines, A. R.; Miller, R. D.; Plocharczyk, E. F.; Rener, G. A.; Richey, R. N.; Schmid, C. R.; Vaid, R. K.; Yu, H. Org. Process Res. Dev. 2012, 16, 982–1002.
Frederick, M. O.; Calvin, J. R.; Cope, R. F.; LeTourneau, M. E.; Lorenz, K. T.; Johnson, M. D.; Maloney, T. D.; Pu, Y. J.; Miller, R. D.; Cziesla, L. E. Org. Process Res. Dev. 2015, 19, 1411–1417.
LaPorte, T. L.; Spangler, L.; Hamedi, M.; Lobben, P.; Chan, S. H.; Muslehiddinoglu, J.; Wang, S. S. Y. Org. Process Res. Dev. 2014, 18, 1492–1502.
Marsini, M. A.; Buono, F. G.; Lorenz, J. C.; Yang, B.-S.; Reeves, J. T.; Sidhu, K.; Sarvestani, M.; Tan, Z.; Zhang, Y.; Li, N.; Lee, H.; Brazzillo, J.; Nummy, L. J.; Chung, J. C.; Luvaga, I. K.; Narayanan, B. A.; Wei, X.; Song, J. J.; Roschangar, F.; Yee, N. K.; Senanayake, C. H. Green Chemistry 2017, 19, 1454–1461.
Harsanyi, A.; Conte, A.; Pichon, L.; Rabion, A.; Grenier, S.; Sandford, G. Org. Process Res. Dev. 2017, 21, 273–276.
Li, C.; Kawamata, Y.; Nakamura, H.; Vantourout, J. C.; Liu, Z.; Hou, Q.; Bao, D.; Starr, J. T.; Chen, J.; Yan, M.; Baran, P. S. Angew. Chem., Int. Ed. Just accepted.
Yan, M.; Kawamata, Y.; Baran, P. S. Angew. Chem., Int. Ed. Just accepted.
Green, R. A.; Pletcher, D.; Leach, S. G.; Brown, R. C. D. Org. Lett. 2016, 18, 1198–1201.
Kabeshov, M. A.; Musio, B.; Murray, P. R. D.; Browne, D. L.; Ley, S. V. Org. Lett. 2014, 16, 4618–4621.
Mijalis, A. J.; Thomas Iii, D. A.; Simon, M. D.; Adamo, A.; Beaumont, R.; Jensen, K. F.; Pentelute, B. L. Nat. Chem. Biol. 2017, 13, 464–466.
Reizman, B. J.; Jensen, K. F. Acc. Chem. Res. 2016, 49, 1786–1796.
Holmes, N.; Akien, G. R.; Blacker, A. J.; Woodward, R. L.; Meadows, R. E.; Bourne, R. A. React. Chem. Eng. 2016, 1, 366–371.
Fitzpatrick, D. E.; Battilocchio, C.; Ley, S. V. Org. Process Res. Dev. 2016, 20, 386–394.
Coley, C. W.; Barzilay, R.; Jaakkola, T. S.; Green, W. H.; Jensen, K. F. ACS Cent. Sci. 2017, 3, 434–443.
Gutmann, B.; Cantillo, D.; Kappe, C. O. Angew. Chem., Int. Ed. 2015, 54, 6688–6728.
Movsisyan, M.; Delbeke, E. I. P.; Berton, J. K. E. T.; Battilocchio, C.; Ley, S. V.; Stevens, C. V. Chem. Soc. Rev. 2016, 45, 4892–4928.
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May, S.A. Flow Chemistry, Continuous Processing, and Continuous Manufacturing: A Pharmaceutical Perspective. J Flow Chem 7, 137–145 (2017). https://doi.org/10.1556/1846.2017.00029
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DOI: https://doi.org/10.1556/1846.2017.00029