Advertisement

Multistep Continuous-Flow Processes for the Preparation of Heterocyclic Active Pharmaceutical Ingredients

  • Romaric Gérardy
  • Jean-Christophe M. MonbaliuEmail author
Chapter
Part of the Topics in Heterocyclic Chemistry book series (TOPICS, volume 56)

Abstract

Flow chemistry has many fascinating facets, among which the most challenging is arguably the implementation of complex multistep processes within one uninterrupted fluidic network. This document provides a thorough overview of some of the most representative examples of multistep continuous-flow strategies in the specific context of preparing heterocyclic active pharmaceuticals. Selected examples emphasizing the implementation of multistep sequences, including various combinations of chemical transformations, purifications, or in-line analysis, are discussed.

Keywords

Flow chemistry Heterocyclic APIs Multistep continuous processes 

References

  1. 1.
    Gutmann B, Elsner P, O’Kearney-McMullan A, Goundry W, Roberge DM, Kappe CO (2015) Org Process Res Dev 19:1062CrossRefGoogle Scholar
  2. 2.
    Shen B, Jamison TF (2012) Org Lett 14:3348CrossRefPubMedGoogle Scholar
  3. 3.
    Zhu C, Tang C, Cao Z, He W, Chen Y, Chen X, Guo K, Ying H (2014) Org Process Res Dev 18:1575CrossRefGoogle Scholar
  4. 4.
    Lee DS, Amara Z, Poliakoff M, Harman T, Reid G, Rhodes B, Brough S, McInally T, Woodward S (2015) Org Process Res Dev 19:831CrossRefGoogle Scholar
  5. 5.
    Hopkin MD, Baxendale IR, Ley SV (2010) Chem Commun 46:2450CrossRefGoogle Scholar
  6. 6.
    Hopkin MD, Baxendale IR, Ley SV (2013) Org Biomol Chem 11:1822CrossRefPubMedGoogle Scholar
  7. 7.
    Yang JC, Niu D, Karsten BP, Lima F, Buchwald SL (2016) Angew Chem Int Ed 55:2531CrossRefGoogle Scholar
  8. 8.
    Holmes N, Akien GR, Blacker AJ, Woodward RL, Meadows RE, Bourne RA (2016) React Chem Eng 1:366CrossRefGoogle Scholar
  9. 9.
    Baxendale IR, Deeley J, Griffiths-Jones CM, Ley SV, Saaby S, Tranmer GK (2006) Chem Commun 24:2566CrossRefGoogle Scholar
  10. 10.
    Pellegatti L, Hafner A, Sedelmeier J (2016) J Flow Chem 6:198CrossRefGoogle Scholar
  11. 11.
    Correia CA, Gilmore K, McQuade DT, Seeberger PH (2015) Angew Chem Int Ed 54:4945CrossRefGoogle Scholar
  12. 12.
    Correia CA, McQuade DT, Seeberger PH (2013) Adv Synth Catal 355:3517CrossRefGoogle Scholar
  13. 13.
    Britton J, Jamison TF (2017) Angew Chem Int Ed 56:8823CrossRefGoogle Scholar
  14. 14.
    Shen B, Bedore MW, Sniady A, Jamison TF (2012) Chem Commun 48:7444CrossRefGoogle Scholar
  15. 15.
    Shen B, Jamison TF (2013) Aust J Chem 66:157CrossRefGoogle Scholar
  16. 16.
    Fan X, Sans V, Yaseneva P, Plaza DD, Williams J, Lapkin A (2012) Org Process Res Dev 16:1039CrossRefGoogle Scholar
  17. 17.
    Yaseneva P, Plaza D, Fan X, Loponov K, Lapkin A (2015) Catal Today 239:90CrossRefGoogle Scholar
  18. 18.
    Lévesque F, Seeberger PH (2012) Angew Chem Int Ed 51:1706CrossRefGoogle Scholar
  19. 19.
    Kopetzki D, Lévesque F, Seeberger PH (2013) Chem Eur J 19:5450CrossRefPubMedGoogle Scholar
  20. 20.
    Gilmore K, Kopetzki D, Lee JW, Horváth Z, McQuade DT, Seidel-Morgenstern A, Seeberger PH (2014) Chem Commun 50:12652CrossRefGoogle Scholar
  21. 21.
    Pieber B, Glasnov T, Kappe CO (2015) Chem Eur J 21:4368CrossRefPubMedGoogle Scholar
  22. 22.
    Kamptmann SB, Ley SV (2015) Aust J Chem 68:693CrossRefGoogle Scholar
  23. 23.
    Lücke D, Dalton T, Ley SV, Wilson ZE (2016) Chem Eur J 22:4206CrossRefPubMedGoogle Scholar
  24. 24.
    Lin H, Dai C, Jamison TF, Jensen KF (2017) Angew Chem Int Ed 56:8870CrossRefGoogle Scholar
  25. 25.
    Herath A, Dahl R, Cosford NDP (2010) Org Lett 12:412CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ingham RJ, Battilocchio C, Hawkins JM, Ley SV (2014) Beilstein J Org Chem 10:641CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bana P, Lakó Á, Kiss NZ, Béni Z, Szigetvári Á, Kóti J, Túrós GI, Éles J, Greiner I (2017) Org Process Res Dev 21:611CrossRefGoogle Scholar
  28. 28.
    Hartwig J, Kirschning A (2016) Chem Eur J 22:3044CrossRefPubMedGoogle Scholar
  29. 29.
    Hartwig J, Ceylan S, Kupracz L, Coutable L, Kirschning A (2013) Angew Chem Int Ed 52:9813CrossRefGoogle Scholar
  30. 30.
    Guetzoyan L, Nikbin N, Baxendale IR, Ley SV (2013) Chem Sci 4:764CrossRefGoogle Scholar
  31. 31.
    Adamo A, Beingessner RL, Behnam M, Chen J, Jamison TF, Jensen KF, Monbaliu J-CM, Myerson AS, Revalor EM, Snead DR, Stelzer T, Weeranoppanant N, Wong SY, Zhang P (2016) Science 352:61CrossRefPubMedGoogle Scholar
  32. 32.
    Bédard AC, Longstreet AR, Britton J, Wang Y, Moriguchi H, Hicklin RW, Green WH, Jamison TF (2017) Bioorg Med Chem 25:6233CrossRefPubMedGoogle Scholar
  33. 33.
    Ewan HS, Iyer K, Hyun S-H, Wleklinski M, Cooks RG, Thompson DH (2017) Org Process Res Dev 21:1566CrossRefGoogle Scholar
  34. 34.
    Qian Z, Baxendale IR, Ley SV (2010) Synlett 505Google Scholar
  35. 35.
    Qian Z, Baxendale IR, Ley SV (2010) Chem Eur J 16:12342CrossRefPubMedGoogle Scholar
  36. 36.
    Zhang P, Russell MG, Jamison TF (2014) Org Process Res Dev 18:1567CrossRefGoogle Scholar
  37. 37.
    Polster CS, Cole KP, Burcham CL, Campbell BM, Frederick AL, Hansen MM, Harding M, Heller MR, Miller MT, Phillips JL, Pollock PM, Zaborenko N (2014) Org Process Res Dev 18:1295CrossRefGoogle Scholar
  38. 38.
    Gérardy R, Winter M, Vizza A, Monbaliu J-CM (2017) React Chem Eng 2:149CrossRefGoogle Scholar
  39. 39.
    Martin AD, Siamaki AR, Belecki K, Gupton F (2015) J Flow Chem 5:145CrossRefGoogle Scholar
  40. 40.
    Suveges NS, de Souza ROMA, Gutmann B, Kappe CO (2017) Eur J Org Chem 24:6511CrossRefGoogle Scholar
  41. 41.
    Gutmann B, Cantillo D, Weigl U, Cox DP, Kappe CO (2017) Eur J Org Chem 914Google Scholar
  42. 42.
    Gutmann B, Weigl U, Cox DP, Kappe CO (2016) Chem Eur J 22:10393CrossRefPubMedGoogle Scholar
  43. 43.
    Borukhova S, Noël T, Hessel V (2016) ChemSusChem 9:67CrossRefPubMedGoogle Scholar
  44. 44.
    Pastre JC, Browne DL, O’Brien M, Ley SV (2013) Org Process Res Dev 17:1183CrossRefGoogle Scholar
  45. 45.
    Baxendale IR, Griffiths-Jones CM, Ley SV, Tranmer GK (2006) Synlett 3:427Google Scholar
  46. 46.
    Tsubogo T, Oyamada H, Kobayashi S (2015) Nature 520:329CrossRefPubMedGoogle Scholar
  47. 47.
    Ghislieri D, Gilmore K, Seeberger PH (2015) Angew Chem Int Ed 54:678Google Scholar
  48. 48.
    Dai C, Snead DR, Zhang P, Jamison TF (2015) J Flow Chem 5:133CrossRefGoogle Scholar
  49. 49.
    Grongsaard P, Bulger PG, Wallace DJ, Tan L, Chen Q, Dolman SJ, Nyrop J, Hoerrner RS, Weisel M, Arredondo J, Itoh T, Xie C, Wen X, Zhao D, Muzzio DJ, Bassan EM, Shultz CS (2012) Org Process Res Dev 16:1069CrossRefGoogle Scholar
  50. 50.
    Chen J, Przyuski K, Roemmele R, Bakale RP (2014) Org Process Res Dev 18:1427CrossRefGoogle Scholar
  51. 51.
    LaPorte TL, Spangler L, Hamedi M, Lobben P, Chan SH, Muslehiddinoglu J, Wang SSY (2014) Org Process Res Dev 18:1492CrossRefGoogle Scholar
  52. 52.
    Fukuyama T, Chiba H, Kuroda H, Takigawa T, Kayano A, Tagami K (2016) Org Process Res Dev 20:503CrossRefGoogle Scholar
  53. 53.
    Amara Z, Poliakoff M, Duque R, Geier D, Franciò G, Gordon CM, Meadows RE, Woodward R, Leitner W (2016) Org Process Res Dev 20:1321CrossRefGoogle Scholar
  54. 54.
    Filipponi P, Ostacolo C, Novellino E, Pellicciari R, Gioiello A (2014) Org Process Res Dev 18:1345CrossRefGoogle Scholar
  55. 55.
    Cole KP, McClary Groh J, Johnson MD, Burcham CL, Campbell BM, Diseroad WD, Heller MR, Howell JR, Kallman NJ, Koenig TM, May SA, Miller RD, Mitchell D, Myers DP, Myers SS, Phillips JL, Polster CS, White TD, Cashman J, Hurley D, Moylan R, Sheehan P, Spencer RD, Desmond K, Desmond P, Gowran O (2017) Science 356:1144CrossRefPubMedGoogle Scholar
  56. 56.
    Dalla-Vechia L, Reichart B, Glasnov T, Miranda LSM, Kappe CO, de Souza ROMA (2013) Org Biomol Chem 11:6806CrossRefPubMedGoogle Scholar
  57. 57.
    Pinho VD, Gutmann B, Miranda LSM, de Souza ROMA, Kappe CO (2014) J Org Chem 79:1555CrossRefPubMedGoogle Scholar
  58. 58.
    Leão RAC, de Lopes RO, de Bezerra MAM, Muniz MN, Casanova BB, Gnoatto SCB, Gosmann G, Kocsis L, de Souza ROMA, de Miranda LSM (2015) J Flow Chem 5:216CrossRefGoogle Scholar
  59. 59.
    Gauthier DR, Sherry BD, Cao Y, Journet M, Humphrey G, Itoh T, Mangion I, Tschaen DM (2015) Org Lett 17:1353CrossRefPubMedGoogle Scholar
  60. 60.
    Chada S, Mandala D, Watts P (2017) J Flow Chem 7:37CrossRefGoogle Scholar
  61. 61.
    Mandala D, Chada S, Watts P (2017) Org Biomol Chem 15:3444CrossRefPubMedGoogle Scholar
  62. 62.
    Longstreet AR, Opalka SM, Campbell BS, Gupton BF, McQuade DT (2013) Beilstein J Org Chem 9:2570CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Carneiro PF, Gutmann B, de Souza ROMA, Kappe CO (2015) ACS Sustain Chem Eng 3:3445CrossRefGoogle Scholar
  64. 64.
    Lau S-H, Galván A, Merchant RR, Battilocchio C, Souto JA, Berry MB, Ley SV (2015) Org Lett 17:3218CrossRefPubMedGoogle Scholar
  65. 65.
    Glasnov TN, Kappe CO (2010) Adv Synth Catal 352:3089CrossRefGoogle Scholar
  66. 66.
    Cantillo D, Moghaddam MM, Kappe CO (2013) J Org Chem 78:4530CrossRefPubMedGoogle Scholar
  67. 67.
    Moghaddam MM, Pieber B, Glasnov T, Kappe CO (2014) ChemSusChem 7:3122CrossRefPubMedGoogle Scholar
  68. 68.
    Cantillo D, Baghbanzadeh M, Kappe CO (2012) Angew Chem Int Ed 51:10190CrossRefGoogle Scholar
  69. 69.
    O’Brien AG, Lévesque F, Seeberger PH (2011) Chem Commun 47:2688CrossRefGoogle Scholar
  70. 70.
    Müller STR, Murat A, Hellier P, Wirth T (2016) Org Process Res Dev 20:495CrossRefGoogle Scholar
  71. 71.
    Battilocchio C, Deadman BJ, Nikbin N, Kitching MO, Baxendale IR, Ley SV (2013) Chem Eur J 19:7917CrossRefPubMedGoogle Scholar
  72. 72.
    Gross TD, Chou S, Bonneville D, Gross RS, Wang P, Campopiano O, Ouellette MA, Zook SE, Reddy JP, Moree WJ, Jovic F, Chopade S (2008) Org Process Res Dev 12:929CrossRefGoogle Scholar
  73. 73.
    Borukhova S, Noël T, Metten B, de Vos E, Hessel V (2013) ChemSusChem 6:2220CrossRefPubMedGoogle Scholar
  74. 74.
    Borukhova S, Noël T, Metten B, de Vos E, Hessel V (2016) Green Chem 18:4947CrossRefGoogle Scholar
  75. 75.
    Chartoire A, Claver C, Corpet M, Krinsky J, Mayen J, Nelson D, Nolan SP, Peñafiel I, Woodward R, Meadows RE (2016) Org Process Res Dev 20:551CrossRefGoogle Scholar
  76. 76.
    Falß S, Tomaiuolo G, Perazzo A, Hodgson P, Yaseneva P, Zakrzewski J, Guido S, Lapkin A, Woodward R, Meadows RE (2016) Org Process Res Dev 20:558CrossRefGoogle Scholar
  77. 77.
    Šterk D, Jukič M, Časar Z (2013) Org Process Res Dev 17:145CrossRefGoogle Scholar
  78. 78.
    Pieber B, Cox DP, Kappe CO (2016) Org Process Res Dev 20:376CrossRefGoogle Scholar
  79. 79.
    Gutmann B, Elsner P, Cox DP, Weigl U, Roberge DM, Kappe CO (2016) ACS Sustain Chem Eng 4:6048CrossRefGoogle Scholar
  80. 80.
    Marsini MA, Buono FG, Lorenz JC, Yang B-S, Reeves JT, Sidhu K, Sarvestani M, Tan Z, Zhang Y, Li N, Lee H, Brazzillo J, Nummy LJ, Chung JC, Luvaga IK, Narayanan BA, Wei X, Song JJ, Roschangar F, Yee NK, Senanayake CH (2017) Green Chem 19:1454CrossRefGoogle Scholar
  81. 81.
    Lv Y, Yu Z, Su W (2011) Org Process Res Dev 15:471CrossRefGoogle Scholar
  82. 82.
    Gutmann B, Gottsponer M, Elsner P, Cantillo D, Roberge DM, Kappe CO (2013) Org Process Res Dev 17:294CrossRefGoogle Scholar
  83. 83.
    Cantillo D, Mateos C, Rincon JA, De Frutos O, Kappe CO (2015) Chem Eur J 21:12894CrossRefPubMedGoogle Scholar
  84. 84.
    Pellegatti L, Sedelmeier J (2015) Org Process Res Dev 19:551CrossRefGoogle Scholar
  85. 85.
    Brasholz M, Johnson BA, Macdonald JM, Polyzos A, Tsanaktsidis J, Saubern S, Holmes AB, Ryan JH (2010) Tetrahedron 66:6445CrossRefGoogle Scholar
  86. 86.
    Brasholz M, MacDonald JM, Saubern S, Ryan JH, Holmes AB (2010) Chem Eur J 16:11471CrossRefPubMedGoogle Scholar
  87. 87.
    Baumann M, Baxendale IR, Brasholz M, Hayward JJ, Ley SV, Nikbin N (2011) Synlett 10:1375Google Scholar
  88. 88.
    Riva E, Rencurosi A, Gagliardi S, Passarella D, Martinelli M (2011) Chem Eur J 17:6221CrossRefPubMedGoogle Scholar
  89. 89.
    Roesner S, Buchwald SL (2016) Angew Chem Int Ed 55:10463CrossRefGoogle Scholar
  90. 90.
    Sniady A, Bedore MW, Jamison TF (2011) Angew Chem Int Ed 50:2155CrossRefGoogle Scholar
  91. 91.
    Venturoni F, Nikbin N, Ley SV, Baxendale IR (2010) Org Biomol Chem 8:1798CrossRefPubMedGoogle Scholar
  92. 92.
    Filipponi P, Baxendale IR (2016) Eur J Org Chem 2000Google Scholar
  93. 93.
    Petersen TP, Mirsharghi S, Rummel PC, Thiele S, Rosenkilde MM, Ritzén A, Ulven T (2013) Chem Eur J 19:9343CrossRefPubMedGoogle Scholar
  94. 94.
    Petersen TP, Ritzén A, Ulven T (2009) Org Lett 11:5134CrossRefPubMedGoogle Scholar
  95. 95.
    Glotz G, Lebl R, Dallinger D, Kappe CO (2017) Angew Chem Int Ed.  https://doi.org/10.1002/anie.201708533
  96. 96.
    Pagano N, Teriete P, Mattmann ME, Yang L, Snyder BA, Cai Z, Heil ML, Cosford NDP (2017) Bioorg Med Chem.  https://doi.org/10.1016/j.bmc.2017.03.061
  97. 97.
    Pagano N, Herath A, Cosford NDP (2011) J Flow Chem 1:28CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Lövei K, Greiner I, Éles J, Szigetvári Á, Dékány M, Lévai S, Novák Z, Túrós GI (2015) J Flow Chem 5:74CrossRefGoogle Scholar
  99. 99.
    Li B, Widlicka D, Boucher S, Hayward C, Lucas J, Murray JC, O’Neil BT, Pfisterer D, Samp L, Van Alsten J, Xiang Y, Young J (2012) Org Process Res Dev 16:2031CrossRefGoogle Scholar
  100. 100.
    May SA, Johnson MD, Braden TM, Calvin JR, Haeberle BD, Jines AR, Miller RD, Plocharczyk EF, Rener GA, Richey RN, Schmid CR, Vaid RK, Yu H (2012) Org Process Res Dev 16:982CrossRefGoogle Scholar
  101. 101.
    Baumann M, Baxendale IR, Kuratli C, Ley SV, Martin RE, Schneider J (2011) ACS Comb Sci 13:405CrossRefPubMedGoogle Scholar
  102. 102.
    Li X, Chen A, Zhou Y, Huang L, Fang Z, Gan H, Guo K (2015) J Flow Chem 5:82CrossRefGoogle Scholar
  103. 103.
    Zamani P, Khosropour AR (2016) Green Chem 18:6450CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Romaric Gérardy
    • 1
  • Jean-Christophe M. Monbaliu
    • 1
    Email author
  1. 1.Center for Integrated Technology and Organic Synthesis, Department of ChemistryUniversity of LiègeLiègeBelgium

Personalised recommendations