Preparation of substituted pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines via a Pictet-Spengler cyclization

Journal of Organic Chemistry

Volumn 70, Issue 23, 2005, Pages 9629-9631

  Duncton, Matthew A J ^a   Smith II, Leon M ^a   Burdzovic Wizeman, Sabina ^a   Burns, Aaron ^a   Hu Liu, Yunyu Mao ^a   Wong, Wai C ^a   Kiselyov, Alexander S ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SUBSTITUTION REACTIONS;

INHIBITORS; PICTET-SPENGLER CYCLIZATION; TYROSINE KINASES;

ORGANIC COMPOUNDS;

1 CHLORO 7,8 DIMETHOXY 10,11 DIHYDRO 5 OXA 2,4,11 TRIAZADIBENZO[A,D]CYCLOHEPTENE; DIAZEPINE DERIVATIVE; PROTEIN TYROSINE KINASE INHIBITOR; PYRIMIDO[4,5 B] 1,4 BENZOXAZEPINE DERIVATIVE; THIAZEPINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HEATING; PICTET SPENGLER REACTION; POLYMERIZATION; REACTION ANALYSIS; REDUCTION; STRUCTURE ANALYSIS;

AZEPINES; CATALYSIS; CYCLIZATION; MOLECULAR STRUCTURE;

EID: 27744581943     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo051419g     Document Type: Article

References (18)

1. (a) Arteaga C. Semin. Oncol. 2003, 30 (Suppl. 1), 3-11.
2. (b) Khalil, M. Y.; Grandis, J, R.; Shin D. M. Expert Rev. Anticancer Ther. 2003, 3, 367-380.
3. Ciardiello, F.; De Vita, F.; Orditura, M. Comunale, D.; Galizia, G. Future Oncology 2005, 1, 173-181.
4. Tamura, K.; Fukuoka, M, Expert Opin. Pharmacother. 2005, 6, 985-993.
5. Blackball, F, H.; Rehman, S,; Thatcher, N. Expert Opin. Pharmacother. 2005, 6, 995-1002.
6. Hadari, Y.; Smith, L. M., II. Patent WO 2005009384, 2005; Chem. Abstr. 2005, 142, 172179.
7. Levkovskaya, L. G.; Sazonov, N. V.; Grineva, N. A.; Mamaeva, I. E.; Serochkina, N. A.; Safonova, T. S. Khim. Geterotsikl. Soedin. 1985, 122-125.
8. For reviews, see: (a) Royer, J.; Bonin, M.; Micouin, L. Chem. Rev. 2004, 104, 2311-2352.
9. (b) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int. Ed. 1998, 37, 1045-1070.
10. (c) Cox, E. D.; Cook, J. M. Chem. Rev. 1995, 95, 1797-1842.
11. For some examples of the Pictet-Spengler reaction being used to prepare seven-membered rings, see: (a) Kundu, B.; Sawant, D.; Partani, P.; Kesarwani, A. P. J. Org. Chem. 2005, 70, 4889-4892.
12. (b) Dancso, A.; Kajtar-Peredy, M.; Szantay, C. J. Heterocycl. Chem. 1989, 26, 1867-1868.
13. (c) Orazi, O. O.; Corral, R. A.; Giaccio, H. J. Chem. Soc., Perkin Trans. 1 1986, 1977-1982.
14. Adams, D. R.; Bentley, J. M.; Davidson, J. E.; Duncton, M. A. J.; Porter, R. H. P. Patent WO 200044753, 2000; Chem. Abstr. 2000, 133, 150579.
15. A sealed tube was used to minimize any loss of dichloromethane during the reaction. The cyclizations were not examined using reaction conditions other than those detailed in this manuscript.
16. For a Friedel-Crafts approach to the synthesis of pyrimido-[4,5-b]-1,4- benzodiazepines, see: Yang, J.; Che, X.; Dang, Q.; Wei, Z.; Gao, S.; Bai, X. Org. Lett. 2005, 7, 1541-1543.
17. The chloro group in compounds 9e-g could also be displaced with nitrogen, oxygen, and sulfur nucleophiles, but no examples are detailed in this paper.
18. This strategy has been well documented for kinase inhibitors containing a quinazoline or quinoline nitrile heterocyclic core. For example, see: Boschelli, D. H. Med. Chem. Rev. - Online 2004, 1, 457-463.