Technical scale synthesis of a new and highly potent thrombin inhibitor

Synthesis

Volumn , Issue 14, 2004, Pages 2367-2375

  Bernard, Harald ^a   Bülow, Gerd ^a   Lange, Udo E W ^b   Mack, Helmut ^b   Pfeiffer, Thomas ^a   Schäfer, Bernd ^a   Seitz, Werner ^a   Zierke, Thomas ^a  

^a BASF SE   (Germany)

^b ABBOTT GMBH AND CO KG   (Germany)

Author keywords

Amino acids; Drugs; Enantiomeric resolution; Heterocycles; Stereoselective synthesis

Indexed keywords

CRYSTALLINE MATERIALS; DRYING; NANOFILTRATION; NITRILE RESINS; ORGANIC COMPOUNDS; SYNTHESIS (CHEMICAL);

CRYSTALLINE COMPLEXES; SPRAY DRYING; THROMBIN INHIBITORS;

ENZYME INHIBITION;

1 (TERT BUTOXYCARBONYL) 4 HYDROXY 2 PYRROLIDINECARBOXYLIC ACID; 2 AMINO 3 CYCLOHEXYLPROPANOIC ACID; CAPTOPRIL; DEHYDROPROLINE; NICOTINONITRILE; PHENPROCOUMON; SACCHARIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG ISOLATION; DRUG STRUCTURE; DRUG SYNTHESIS; NANOFILTRATION; SPRAY DRYING; STEREOCHEMISTRY;

EID: 5644287536     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-831200     Document Type: Article

References (75)

1. (a) Sorbera, L. A.; Bayes, M.; Castaner, J.; Silvestre, J. Drugs Future 2001, 12, 1155.
2. (b) Pfau, R. Curr. Opin. Drug Disc. 2003, 6, 437.
3. (c) Sanderson, P. E. J.; Stanton, M. G.; Dorsey, B. D.; Lyle, T. A.; McDonough, C.; Sanders, W. M.; Savage, K. L.; Naylor-Olsen, A. M.; Krueger, J. A.; Lewis, S. D.; Lucas, B. J.; Lynch, J. J.; Yan, Y. Bioorg. Med. Chem. Lett. 2003, 13, 795.
4. (d) Olsen, J. A.; Banner, D. W.; Seiler, P.; Obst Sander, U.; D'Arcy, A.; Stihle, M.; Müller, K.; Diederich, F. Angew. Chem. Int. Ed. 2003, 42, 2507.
5. (e) Nilsson, J. W.; Kvarnström, I.; Musil, D.; Nilsson, I.; Samulesson, B. J. Med. Chem. 2003, 46, 3985.
6. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed.; Colman, R. W.; Hirsch, J.; Marder, V. J.; Salzman, E. W., Eds.; Lippincott J. B.: Philadelphia, 1994.
7. (a) Wiley, M. R.; Fisher, M. J. Exp. Opin. Ther. Patents 1997, 7, 1265.
8. (b) Rewinkel, J. B. M.; Adang, A. E. P. Curr. Pharm. Design 1999, 5, 1043.
9. (a) Böhm, H.-J.; Hoeffken, H. W.; Hornberger, W.; Koser, S.; Mack, H.; Pfeiffer, T.; Seitz, W.; Zierke, T. World Patent 9625426, 1995; Chem. Abstr. 1996, 125, 301605.
10. (b) Lange, U. E. W.; Baucke, D.; Hornberger, W.; Mack, H.; Seitz, W.; Höffken, W. Bioorg. Med. Chem. Lett. 2003, 13, 2029.
11. (c) Lange, U. E. W.; Baucke, D.; Hornberger, W.; Mack, H.; Seitz, W.; Höffken, W., manuscript in preparation.
12. Lit. Ref.4a, Example 32 and 93.
13. Rüeger, H.; Benn, M. H. Can. J. Chem. 1982, 60, 2918.
14. Barker, P. L.; Gendler, P. L.; Rapoport, H. J. Org. Chem. 1981, 46, 2455.
15. (a) Wissmann, H.; Kleiner, H.-J. Angew. Chem., Int. Ed. Engl. 1980, 79, 133; Angew. Chem. 1980, 92, 129.
16. (a) Wissmann, H.; Kleiner, H.-J. Angew. Chem., Int. Ed. Engl. 1980, 79, 133; Angew. Chem. 1980, 92, 129.
17. (b) Wissmann, H. Phosphorus and Sulfur 1987, 30, 645.
18. (c) Escher, R.; Bünning, P. Angew. Chem., Int. Ed. Engl. 1986, 25, 277; Angew. Chem. 1986, 98, 264.
19. (c) Escher, R.; Bünning, P. Angew. Chem., Int. Ed. Engl. 1986, 25, 277; Angew. Chem. 1986, 98, 264.
20. (a) Engbersen, J. F. J.; Koudijs, A.; Joosten, M. H. A.; van der Plas, H. C. J. Heterocycl. Chem. 1986, 13, 989.
21. (b) Takamizawa, S.; Wakasa, N.; Fuchikami, T. Synlett 2001, 1623.
22. (c) Bullock, M. W.; Hand, J. J.; Stokstad, E. L. R. J. Am. Chem. Soc. 1956, 78, 3693.
23. (d) Atkins, H.; Wolff, I. A.; Pavlic, A.; Hutchinson, E. J. Am. Chem. Soc. 1944, 66, 1293.
24. (e) Hilpert, K.; Ackermann, J.; Banner, D. W.; Gast, A.; Gubernator, K.; Hadváry, P.; Labler, L.; Müller, K.; Schmid, G.; Tschopp, T. B.; van der Waterbeemd, H. J. Med. Chem. 1994, 37, 3889.
25. Bouchet, M.-J.; Rendon, A.; Wermuth, C. G.; Goeldner, M.; Hirth, C. J. Med. Chem. 1987, 30, 2222.
26. (a) Minisci, F.; Galli, R. Tetrahedron Lett. 1965, 6, 433.
27. (b) Minisci, F. Synthesis 1973, 1.
28. (c) Minisci, F.; Citterio, A.; Vismara, E.; Giordano, C. Tetrahedron 1985, 41, 4157.
29. Houssin, R.; Bernier, J.-L.; Hénichart, J.-P. Synthesis 1988, 259.
30. Donohoe, T. J.; Guyo, P. M. J. Org. Chem. 1996, 61, 7664.
31. Harbuck, J. W.; Rapoport, H. J. Org. Chem. 1972, 37, 3618.
32. Bailey, D. M.; Johnson, R. E.; Albertson, N. F. Org. Synth. 1971, 51, 100.
33. Grehn, L.; Ragnarsson, U. Angew. Chem. Int. Ed. Engl. 1984, 23, 296; Angew. Chem. 1984, 96, 291.
34. Grehn, L.; Ragnarsson, U. Angew. Chem. Int. Ed. Engl. 1984, 23, 296; Angew. Chem. 1984, 96, 291.
35. Stürmer, R.; Schäfer, B.; Wolfart, V.; Stahr, H.; Kazmaier, U.; Helmchen, G. Synthesis 2001, 46.
36. (a) Dormay, J.-R.; Castro, B.; Chappuis, G.; Fritschi, U.-S.; Grogg, P. Angew. Chem. Int. Ed. Engl. 1980, 19, 742; Angew. Chem. 1980, 92, 761.
37. (a) Dormay, J.-R.; Castro, B.; Chappuis, G.; Fritschi, U.-S.; Grogg, P. Angew. Chem. Int. Ed. Engl. 1980, 19, 742; Angew. Chem. 1980, 92, 761.
38. (b) Dormay, J.-R. Synthesis 1982, 753.
39. Pfeiffer, T.; Seitz, W.; Mack, H.; Zierke, T.; Balkenhohl, F.; Lange, U. German Patent 19630082, 1996; Chem. Abstr. 1998, 128, 154380.
40. CAUTION! Thermal runaway reaction with NaH and DMF are known in literature: (a) DeWall, G. Chem. Eng. News 1982, 60(37), 5.
41. (b) DeWall, G. Chem. Eng. News 1982, 60(37), 43.
42. (c) Buckley, J.; Webb, R. L.; Laird, T.; Ward, R. J. Chem. Eng. News 1982, 60(28), 5.
43. (d) Bretherick, L. Handbook of Reactive Chemical Hazards, 4th ed.; Butterworth-Heinemann Ltd.: Boston, 1990, 1181.
44. (a) Jones, M. F. J. Chem. Soc., Perkin Trans. 1 1991, 2479.
45. (b) Rapoport, H. J. Org. Chem. 1994, 54, 394.
46. (a) Pinner, A. Ber. Dtsch. Chem. Ges. 1885, 18, 2845.
47. (b) Stilz, H. U.; Jablonka, B.; Just, M.; Knolle, J.; Paulus, E. F.; Zoller, G. J. Med. Chem. 1996, 39, 2118.
48. Schaefer, F. C.; Peters, G. A. J. Org. Chem. 1961, 26, 412.
49. (a) Medwid, J. B. J. Med. Chem. 1990, 33, 1230.
50. (b) Soula, C.; Marsura, A.; Luu-Duc, C. J. Pharm. Belg. 1987, 42, 293; Chem. Abstr. 1988, 109, 109969.
51. (b) Soula, C.; Marsura, A.; Luu-Duc, C. J. Pharm. Belg. 1987, 42, 293; Chem. Abstr. 1988, 109, 109969.
52. (c) Hullin, R. P.; Miller, J.; Short, W. F. J. Org. Chem. 1947, 12, 394.
53. (d) Thurkauf, A. J. Labelled Compd. Radiopharm. 1997, 39, 123.
54. (e) Garigipati, R. S. Tetrahedron Lett. 1990, 31, 1969.
55. (f) Moss, R. A.; Ma, W.; Merrer, D. C.; Xue, S. Tetrahedron Lett. 1995, 36, 8761.
56. (g) Kirby, J. B.; van Dantzig, N. A.; Chang, C. K.; Nocera, D. G. Tetrahedron Lett. 1995, 36, 3477.
57. (a) Jendralla, H.; Seuring, B.; Herchen, J.; Kulitzscher, B.; Wunner, J.; Stüber, W.; Koschinsky, R. Tetrahedron 1995, 51, 12047.
58. (b) Judkins, B. D.; Allen, D. G.; Cook, T. A.; Evans, B.; Sardharwalla, T. A. Synth. Commun. 1996, 26, 4351.
59. (c) Bolton, R. E.; Coote, S. J.; Finch, H.; Lowdon, H.; Pegg, N.; Vinader, M. V. Tetrahedron Lett. 1995, 36, 4471.
60. Partridge, M. W.; Short, W. F. J. Org. Chem. 1947, 72, 390.
61. Lange, U. E. W.; Schäfer, B.; Baucke, D.; Buschmann, E.; Mack, H. Tetrahedron Lett. 1999, 40, 7067.
62. Moser, H.; Fliri, A.; Steiger, A.; Costello, G.; Schreiber, J.; Eschenmoser, A. Helv. Chim. Acta 1986, 69, 1224.
63. (a) Bergeron, H. J.; Niegard, J.; Dichs, J. B.; Egli-Karmakka, M.; Frei, J.; Huxley-Tencer, A.; Peter, H. H. J. Med. Chem. 1991, 34, 2072.
64. (b) Kwiatkowski, S.; Crocker, P. J.; Chavan, A. J.; Imai, N.; Haley, B. E.; Watt, D. S. Tetrahedron Lett. 1990, 31, 2093.
65. (c) Ehrler, J.; Farooq, S. Synlett 1994, 702.
66. Reviews: (a) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed. 2001, 40, 3726; Angew. Chem. 2001, 113, 3840.
67. Reviews: (a) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed. 2001, 40, 3726; Angew. Chem. 2001, 113, 3840.
68. (b) Jarvo, E. R.; Miller, S. J. Tetrahedron 2002, 58, 2481.
69. Henecka, H.; Kurtz, P. In Houben-Weyl Methoden der Organischen Chemie, 4th ed., Vol. 8; Thieme: Stuttgart, 1952, 703.
70. For ion exchange chromatography an acetate ion exchanger from BIO RAD was used: AG 1-X8 Resin, 100-200 mesh, acetate form (catalog-Mr.: 140-1443) Address: BIO RAD (BIO RAD laboratories, 2000 Alfred Nobel Dr., Hercules, CA 94547. Due to the water content (48%) before chromatography the ion exchanger was treated with an excess of anhyd MeOH. Based on the content of acetate more than two equivalents were used. The column should be thin and long. For ion exchange chromatography MeOH was used as the solvent.
71. (a) Razdan, U.; Shah, V. J. J. Sci. Ind. Res. 2001, 60, 560.
72. (b) Dijkstra, H. P.; van Klink, G. P. M.; van Koten, G. Acc. Chem. Res. 2002, 35, 798.
73. Schäfer, B.; Harms, G.; Ascherl, H.; Krei, G. A. World Patent 200068254, 1999; Chem. Abstr. 2000, 133, 366431.
74. Schäfer, B. European Patent 1054017, 1999; Chem. Abstr. 2000, 133, 366468.
75. ICH Guideline Q7A: http://www.fda.gov/cder/guidance/ 1289dft.pdf.