Resolution of δ-lactams provides access to nonracemic benzoquinolinones: The synthesis of LY300502 and LY300503

Journal of Organic Chemistry

Volumn 61, Issue 13, 1996, Pages 4450-4454

  Astleford, Bret A ^a   Audia, James E ^a   Deeter, Jack ^a   Heath, Perry C ^a   Janisse, Samantha K ^a   Kress, Thomas J ^a   Wepsiec, James P ^a   Weigel, Leland O ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

8 CHLORO 1,2,3,4,4A,5,6,10B OCTAHYDRO 4 METHYLBENZO[F]QUINOLIN 3(2H) ONE; UNCLASSIFIED DRUG;

ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; ENANTIOMER; STEREOCHEMISTRY;

EID: 0030059087     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9601425     Document Type: Article

References (44)

1. (a) For synthesis and SAR of LY191704, see: Jones, C. D.; Audia, J. E.; Hirsch, K. S.; Lawhorn, D. E.; McQuaid, L. A.; Neubauer, B. L.; Pike, A. J.; Pennington, P. A.; Stamm, N. B.; Toomey, R. E. J. Med. Chem. 1993, 36, 421.
2. (b) Neubauer, B. L.; Goode, R. L.; Gray, H. M.; Hanke, C. W.; Hirsch, K. S.; Hsiao, K. C.; Jones, C. D.; Lawhorn, D. E.; McQuaid, L.; Toomey, R. E.; Valia, K.; Audia, J. E. Drugs Future, 1995, 20, 144.
3. (c) Hirsch, K. S.; Jones, C. D. EP Appl. 531026, August 20, 1992.
4. (a) Hirsch, K. S.; Jones, C. D.; Audia, J. E.; Anderson, S.; McQuaid, L.; Stamm, N. B.; Pennington, P.; Russell, D. W.; Neubauer, B. L.; Toomey, R. E. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5277.
5. (b) Holt, D. A.; Levy, M. A.; Ladd, D. L.; Erb, J. M.; Heaslip, J. I.; Brandt, M.; Metcalf, B. W. J. Med. Chem. 1990, 33, 937.
6. Rasmusson, G. H.; Reynolds, G. F.; Steinberg, N. G.; Walton, E.; Patel, G. F.; Liang, T.; Casccieri, M. A.; Cheeung, A. H.; Brooks, J. R.; Berman, C. J. Med. Chem. 1986, 29, 2298.
7. Weigel, L. O.; Astleford, B. A. Chirality in Industry - II; Collins, A. N., Crosby, J., Sheldrake, G. N., Ed.; Wiley: New York, 1996, in press.
8. (a) Stork, G. Pure Appl. Chem. 1968, 17, 383.
9. (b) Stork, G.; Kretchmer, R. A.; Schlessinger, R. H. J. Am. Chem. Soc. 1968, 90, 1647.
10. (c) Ninomiya, I.; Higuchi, S.; Mori, T. J. Chem. Soc., Chem. Commun. 1971, 457.
11. (d) El-Barbary, A. A.; Carlsson, S.; Lawesson, S. O. Tetrahedron 1982, 405.
12. (e) Review of enamine mediated aza-annulation: Stille, J. R.; Barta, N. S. In Studies in Natural Products Chemistry; Rahman, A., Ed.; Elsevier: New York, 1996; Vol. 17, in press.
13. (a) Cannon, J. G.; Chang, Y.; Amoo, V. E.; Walker, K. A. Synthesis 1986, 494.
14. (b) Using isomer-free 8, we conducted a series of reductions isothermally without solvent (to increase rate) and measured the % of cis-13: temperature °C, (% cis): -15° (2-3%); 0° (7-9%); 34° (14%); 83° (18%).
15. (a) Nixon, J. A.; Pioch, R. P.; Schaus, J. M.; Titus, R. D., European Pat. Appl. EP 343830 A2, November 29, 1989.
16. (b) For the preparation of 6-chloro-2-tetralone, see Rosowsky, A.; Battiglia, J; Chen, K. K. N.; Modest, E. J. J. Org. Chem. 1968, 33, 4288. (c) Suryawanshi, S. N.; Fuchs, P. L. J. Org. Chem. 1986, 51, 902.
17. (b) For the preparation of 6-chloro-2-tetralone, see Rosowsky, A.; Battiglia, J; Chen, K. K. N.; Modest, E. J. J. Org. Chem. 1968, 33, 4288. (c) Suryawanshi, S. N.; Fuchs, P. L. J. Org. Chem. 1986, 51, 902.
18. (a) Astleford, B. A.; Deeter, J.; Kress, T. J.; Janisse, S. K.; Weigel, L. O.; Wepsiec, J. P. 206th National American Chemical Society Meeting, Chicago, IL ORGN075, August 23, 1993.
19. (b) When the aza-annulation with β-tetralone was performed in our labs, the yield reported by Ninomiya was reproduced. The isomer distribution derived from 5 is due, in part, to the inductive/resonance effects of the 6-halogen substituent.
20. For similar observations of regioselectivity in the alkylation of tetralone enamines due to 1-8 peri-effects, see: (a) Volpe, T.; Revial, G.; Pfau, M.; d'Angelo, J. Tetrahedron Lett. 1987, 28, 2367. (b) d'Angelo, J. Tetrahedron Lett. 1988, 29, 4427.
21. For similar observations of regioselectivity in the alkylation of tetralone enamines due to 1-8 peri-effects, see: (a) Volpe, T.; Revial, G.; Pfau, M.; d'Angelo, J. Tetrahedron Lett. 1987, 28, 2367. (b) d'Angelo, J. Tetrahedron Lett. 1988, 29, 4427.
22. (a) The ratio of 8 to 10 was measured throughout the reaction (10 mmol, 5 equiv of acrylamide and 3 mol % of TsOH, 87 °C): time h, (8:10); 2.5 (94:6); 6 (92:8); 144 (85:15).
23. (b) The pyrrolidine released underwent Michael addition to acrylamide (exothermic) at a faster rate than aza-annulation. These results suggest that use of 1.75 equiv of acrylamide as recommended by Ninomiya (see ref 5c) represents 88% of theory for complete conversion. A patent reported that 2.4 equiv of acrylamide was optimal: Tanabe Seiyaku KK JP-48023779, March 27, 1973.
24. (a) Cannon reported three isomers from aza-annulation with 8-methoxy-2-tetralone and acrylamide (total yield 30%, ratio of 19:20: 21, 77:17:6). Reduction (TES-TFA) of 19 and 21 reportedly gave the trans isomer but 20 gave the cis isomer. Cannon, J. G.; Kirschbaum, K. S. Synthesis 1993, 1151.
25. (b) Mellin reported the mixture from ref 11a gave 65:35 cis/trans mixture upon reduction with TES-TFA: Mellin, C.; Vallagrda, J.; Nelson, D. L.; Bjork, L.; Yu, H.; Anden, N. E.; Csoregh, L.; Arvidsson, L. E.; Hacksell, U. J. J. Med. Chem. 1991, 34, 497.
26. (c) The spectral data of 6 was similar to the data for structure II in reference 11a. We are exploring the results of the aza-annulation and reduction sequence reported by Cannon (ref lia) and Mellin (ref 11b). (Matrix Presented)
27. -3. The data was collected on an automated four-circle diffractomer using monochromatic copper radiation. The structure was solved with the use of direct methods and was refined by least-squares with anisotropic temperature factors for all atoms except hydrogen. All hydrogen atoms were included at calculated positions. The final R-factor was 0.05. An ORTEP plot of trans-(±)-11 is included in the supporting information. The author has deposited atomic coordinates for this structure with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, on request, from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
28. The formation of TFA complexes provided a useful method for isolation and purification of a number of related benzoquinolinone derivatives. Unpublished observations, L. Weigel.
29. Kress, T. J. Unpublished material.
30. Audia, J. E.; Lawhorn, D. E.; Deeter, J. B. Tetrahedron Lett. 1993 34, 7001.
31. Abel, A. D.; Erhard, K. F.; Yen, H. K.; Yamashita, D. S.; Brandt, M.; Mohammed, H.; Levey, M. A.; Holt, D. A. Bioorg. Med. Chem. Lett. 1994, 1365.
32. (a) Audia, J. E.; Jones, C. D.; McQuaid, L.; Weigel, L. US 5 334 767 August 2, 1994.
33. (b) For methanolysis of N-BOC-δ-lactams under basic conditions, see: Flynn, D. L.; Zelle, R. E.; Grieco, P. A. J. Org. Chem. 1983, 48, 2424. (c) For ring-opening of N-tosyl lactams, see: Bon, E.; Bigg, D. C. H.; Betrand, G. J. Org. Chem. 1994, 59, 1904 and references therein. (d) For acid-catalyzed methanolysis of N-acyl lactams see Dixit, N. A.; Tandel, S. K.; Rajappa, S. Tetrahedron Lett. 1994 35, 6133. (e) For reversal of the selectivity in reference 17b, see: Wei, Z. Y.; Knaus, E. E. Tetrahedron Lett. 1994 35, 847.
34. (b) For methanolysis of N-BOC-δ-lactams under basic conditions, see: Flynn, D. L.; Zelle, R. E.; Grieco, P. A. J. Org. Chem. 1983, 48, 2424. (c) For ring-opening of N-tosyl lactams, see: Bon, E.; Bigg, D. C. H.; Betrand, G. J. Org. Chem. 1994, 59, 1904 and references therein. (d) For acid-catalyzed methanolysis of N-acyl lactams see Dixit, N. A.; Tandel, S. K.; Rajappa, S. Tetrahedron Lett. 1994 35, 6133. (e) For reversal of the selectivity in reference 17b, see: Wei, Z. Y.; Knaus, E. E. Tetrahedron Lett. 1994 35, 847.
35. (b) For methanolysis of N-BOC-δ-lactams under basic conditions, see: Flynn, D. L.; Zelle, R. E.; Grieco, P. A. J. Org. Chem. 1983, 48, 2424. (c) For ring-opening of N-tosyl lactams, see: Bon, E.; Bigg, D. C. H.; Betrand, G. J. Org. Chem. 1994, 59, 1904 and references therein. (d) For acid-catalyzed methanolysis of N-acyl lactams see Dixit, N. A.; Tandel, S. K.; Rajappa, S. Tetrahedron Lett. 1994 35, 6133. (e) For reversal of the selectivity in reference 17b, see: Wei, Z. Y.; Knaus, E. E. Tetrahedron Lett. 1994 35, 847.
36. (b) For methanolysis of N-BOC-δ-lactams under basic conditions, see: Flynn, D. L.; Zelle, R. E.; Grieco, P. A. J. Org. Chem. 1983, 48, 2424. (c) For ring-opening of N-tosyl lactams, see: Bon, E.; Bigg, D. C. H.; Betrand, G. J. Org. Chem. 1994, 59, 1904 and references therein. (d) For acid-catalyzed methanolysis of N-acyl lactams see Dixit, N. A.; Tandel, S. K.; Rajappa, S. Tetrahedron Lett. 1994 35, 6133. (e) For reversal of the selectivity in reference 17b, see: Wei, Z. Y.; Knaus, E. E. Tetrahedron Lett. 1994 35, 847.
37. (a) Astleford, B. A.; Audia, J. E.; Dunigan, J. M.; Janisse, S. K.; Kennedy, J.; Kress, T. J.; Waggoner, R.; Wepsiec, J. P.; Weigel, L. O. 206th National American Chemical Society Meeting, Chicago, IL ORGN76, August 23, 1993.
38. (b) Attempted resolution of the nonmethylated 12 using the resolution sequence shown in eq 4 was problematic due to facile lactamization.
39. For a similar approach involving enzymatically mediated closure of amino esters to lactams, see Gutman, A. L.; Meyer, E.; Yue, X.; Abell, C. Tetrahedron Lett. 1992, 33, 3943.
40. 3H, etc.) catalyzed the methanolysis but gave nonvolatile sulfonic acid esters (e.g. TsOMe) which are toxic and problematic during purification of intermediates.
41. Kuo, F.; Wheeler, W. J. J. Labeled Compd. Radiopharm. 1994, 34, 915.
42. Weigel, L. O. 12th Process Development Symposium, Robinson College, Cambridge, England, December 12, 1994.
43. 254 (0.25 mm) using ethyl acetate-hexane-methanol (50:50:1) with a Shimadzu CS-930 Scanner 255 nm or 520 nm after development with phosphomolybdic acid.
44. Compounds 1, 3, and 4 (although chemically pure) often exhibit poor melting point and DSC behavior due to polymorphism. Unpublished data of M. Kearns, C. Pasini, and L. Weigel.