Solid phase synthesis of 1,4-benzodiazepine-2,5-diones

Tetrahedron Letters

Volumn 37, Issue 45, 1996, Pages 8081-8084

  Mayer, John P ^a   Zhang, Jingwen ^a   Bjergarde, Kirsten ^a   Lenz, Doug M ^a   Gaudino, John J ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZODIAZEPINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0030569368     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01845-X     Document Type: Article

References (18)

1. 1. Several excellent reviews highlighting advances in combinatorial chemistry have been published recently. These include a) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96 , 555.
2. b) Special issue on combinatorial chemistry, Acc. Chem. Res , 1996, 29 , 111.
3. c) Fruchtel, J. S.; Jung, G. Angew. Chem. Int. Ed. Engl. 1996, 35 , 17. For solution-phase approaches to combinatorial chemistry see: Cheng, S.; Comer, D. D.; Williams, J. P.; Myers, P. L.; Boger, D. L. J. Am. Chem. Soc. 1996, 118 , 2567.
4. c) Fruchtel, J. S.; Jung, G. Angew. Chem. Int. Ed. Engl. 1996, 35 , 17. For solution-phase approaches to combinatorial chemistry see: Cheng, S.; Comer, D. D.; Williams, J. P.; Myers, P. L.; Boger, D. L. J. Am. Chem. Soc. 1996, 118 , 2567.
5. 2. Carabateas, P. M.; Harris, L. S. J. Med. Chem. 1966, 9 , 6.
6. 3. Cho, N. S.; Song, K. Y.; Parkanyi, C. J. Heterocycl. Chem. 1989, 26 , 1897.
7. 4. McDowel, R. S.; Blackburn, B. K.; Gadek, T. R.; McGee, L. R.; Rawson, T.; Reynolds, M. E.; Robarge, K. D.; Somers, T. C.; Thorsett, E. D.; Tischler, M.; Webb, R. R., II; Venuti, M. C. J. Am. Chem. Soc. 1994, 116, 5077.
8. 5. Aquino, C. J.; Dezube, M.; Sugg, E. E.; Sherrill, R. G.; Willson, T. M.; Szewczyk, J. R. Int. Pat. Appl. WO 9528399.
9. 6. a) Boojamra, C. G.; Burow, K. M.; Ellman, J. A. J. Org. Chem. 1995, 60 , 5742.
10. b) Goff, D. A.; Zuckermann, R. N. J. Org. Chem. 1995, 60 , 5744. For an approach to this heterocycle using a novel "resin capture" strategy see : Keating, T. A.; Armstrong, R. W.; J. Am. Chem. Soc. 1996, 118 , 257.
11. b) Goff, D. A.; Zuckermann, R. N. J. Org. Chem. 1995, 60 , 5744. For an approach to this heterocycle using a novel "resin capture" strategy see : Keating, T. A.; Armstrong, R. W.; J. Am. Chem. Soc. 1996, 118 , 257.
12. 7. Wang, S. S. J. Am. Chem. Soc. 1973, 95, 1328.
13. 8. Fmoc-anthranilic acid is commercially available from Advanced ChemTech (Louisville, KY), additional derivatives were prepared from the appropriate anthranilic acid and Fmoc-chloride.
14. 9. Meyers, H. V.; Dilley, G. J.; Durgin, T. L.; Powers, S. T.; Winsinger, N. A.; Zhu, H.; Pavia, M. R. Molecular Diversity, 1995, 1, 13.
15. 10. Analysis by chiral chromatography (Phenomenex Chirex column, 3.2 × 250mm, 60:35:5 hexane /dichloromethane /ethanol elution mixture with integration of peak areas at 254nm) revealed partial racemization under these reaction conditions. For example, cmpds. 2 and 3 exhibited enantiomeric excess values of 77% and 56% respectively.
16. 6) δ 10.40 (s, 1H), 8.49 (d, 1H, J=6Hz), 7.66 (d, 1H, J=6Hz), 7.51(dd, J=8Hz, J= 1.5Hz), 7.32-7.17 (m, 6H), 7.1 (d, 1H, J= 7.5Hz), 3.90 (ddd, 1H, J=5.5Hz, J=5Hz, J=5Hz), 3.14 (dd, 1H, J= 14Hz, J=5.5Hz), 2.86 (dd, 1H, J= 14Hz, J=5Hz). Electrospray mass spectral characterization: 267 [MH+], calc. : 266.
17. 18 column, 4.6 × 250mm, 0-50% acetonitrile/water containing 0.1% TFA with integration of peak areas at 220nm.)
18. b) yields were calculated from the weight of crude material and the initial loading level of starting Wang resin.