Utility of Complementary Molecular Reactivity and Molecular Recognition (CMR/R) Technology and Polymer-Supported Reagents in the Solution-Phase Synthesis of Heterocyclic Carboxamides

Journal of Organic Chemistry

Volumn 62, Issue 17, 1997, Pages 5908-5919

  Parlow, John J ^a   Mischke, Deborah A ^a   Woodard, Scott S ^a  

^a MONSANTO COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001768317     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo970571i     Document Type: Article

References (60)

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7. For reviews, see: (a) Fenniri, H. Curr. Med. Chem. 1996, 3 (5), 343. (b) Schultz, J. S.; Schultz, J. S. Biotechnol. Prog. 1996, 12 (6), 729. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555. (d) Doyle, P. M. J. Chem. Technol. Biotechnol. 1995, 64, 317. (e) Terrett, N. K.; Gardner, M.; Gordon, D. W.; Kobylecki, R. J.; Steele, J. Tetrahedron 1995, 51, 8135. (f) Gordon, L. Chem. Soc. Rev. 1995, 24, 309. (g) Doyle, P. M. J. Chem. Technol. Biotechnol. 1995, 64, 317. (h) Harris, J. C. Biologicals Immunologicals 1995, 469. (i) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res. 1996, 29, 144. (j) Fruechtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17. For examples, see: (k) Look, G. C.; Schullek, J. R.; Holmes, C. P.; Chinn, J. P.; Gordon, E. M.; Gallop, M. A. Bioorg. Med. Chem. Lett. 1996, 6, 707. (l) Gordeev, M. F.; Patel, D. V.; Gordon, E. M. J. Org. Chem. 1996, 67, 924. (m) Cao, X.; Moran, E. J.; Siev, D.; Lio, A.; Ohashi, C.; Majalli, A. M. M. Bioorg. Med. Chem. Lett. 1995, 5, 2953. (n) Wang, G. T.; Li, S.; Wideburg, N.; Krafft, G. A.; Kempf, D. J. J. Med. Chem. 1995, 38, 2995.
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39. (g) An, H.; Cook, P. D. Tetrahedron Lett. 1996, 37, 7233.
40. (h) Boger, D. L.; Tarby, C. M.; Myers, P. L.; Caporale, L. H. J. Am. Chem. Soc. 1996, 118, 2109.
41. (i) Kaldor, S. W.; Fritz, J. E.; Tang, J.; McKinney, E. R. Bioorg. Med. Chem. Lett. 1996, 6, 3041.
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45. (m) Smith, P. W.; Lai, J. Y. Q.; Whittington, A. R.; Cox, B.; Houston, J. G.; Stylli, C. H.; Banks, M. N.; Tiller, P. R. Bioorg. Med. Chem. Lett. 1994, 4, 2821.
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47. Other reported similar strategies include: (a) Booth, R. J.; Hodge, J. C. J. Am. Chem. Soc. 1997, 119, 4882-4886. (b) Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513. (c) Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193.
48. Other reported similar strategies include: (a) Booth, R. J.; Hodge, J. C. J. Am. Chem. Soc. 1997, 119, 4882-4886. (b) Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513. (c) Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193.
49. Other reported similar strategies include: (a) Booth, R. J.; Hodge, J. C. J. Am. Chem. Soc. 1997, 119, 4882-4886. (b) Gayo, L. M.; Suto, M. J. Tetrahedron Lett. 1997, 38, 513. (c) Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193.
50. (a) Parlow, J. J.; Normansell, J. E. Mol. Diversity 1996, 1, 271.
51. (b) Parlow, J. J.; Woodard, S. S.; Mischke, D. A.; Normansell, J. E. U.S. Patent Application 08/623,444.
52. The terms reactant and reagent have explicit meanings in the context of this strategy. A reactant is a starting material which becomes chemically incorporated into the product. A reagent is a chemical which mediates a transformation but does not become incorporated into the product.
53. Desai, M. C.; Stramiello, S. L. M. Tetrahedron Lett. 1993, 34, 7685.
54. Further experiments demonstrated that succinic anhydride and tetrafluorophthalic anhydride also worked to derivatize the aniline for removal.
55. 1H NMR.
56. 13
57. Hamper, B. C.; Kurtzweil, M. L.; Beck, J. P. J. Org. Chem. 1992, 57, 5680.
58. The Friedel-Crafts acylation reactions (Scheme 7) afforded regioisomers in several cases and were purified at some point in the synthesis. The two exceptions are compounds 38j,k, in which each contains a mixture of regioisomers.
59. It took an equivalent of one person working 7 months for both validation and generation of the 400-membered library.
60. Seki, S.; Yamaguchi, H.; Nakamura, Y.; Kubo, H. Japanese Patent SHO 57-106665, 1982.