Bromine-Promoted cyclization of an olefinic α-Aminonitrile: A practical synthesis of 5-Aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (ADCI)

Tetrahedron Letters

Volumn 37, Issue 48, 1996, Pages 8655-8658

  Gonzalez, Javier ^a   Carroll, F Ivy ^a  

^a RTI INTERNATIONAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINOCARBONYL 10,11 DIHYDRO 5H DIBENZO[A,D]CYCLOHEPTEN 5,10 IMINE; ANTICONVULSIVE AGENT; UNCLASSIFIED DRUG;

ARTICLE; CYCLIZATION; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030602188     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02002-3     Document Type: Article

References (15)

1. 1. (a) Rogawski, M. A.; Thurkauf, A.; Yamaguchi, S.; Rice, K. C.; Jacobson, A. E.; Mattson, M. V. J. Pharmacol. Exp. Ther. 1989, 249, 708-712.
2. (b) Monn, J. A.; Thurkauf, A.; Mattson, M. V.; Jacobson, A. E.; Rice, K. C. J. Med. Chem. 1990, 33, 1069.
3. 2. Georgiadis, M. P.; Haroutounian, S. A. Synthesis 1989, 616.
4. 4 described by Brenner, D. G.; Cravolowsky, K. M.; Shepard, K. L. J. Heterocycl. Chem. 1985, 22, 805.
5. 4. Alternatively, exposure of 5 to sodium cyanide in the presence of chlorotrimethylsilane, pyridine and potassium iodide in acetonitrile at 25 °C for 16 h afforded 6 in 67% yield after a basic aqueous workup. Similar conditions have been used in the synthesis of trimethylsilylcyanide: Duboudin, F.; Cazeau, P.; Moulines, F.; Laporte, O. Synthesis 1982, 212.
6. 5. In a related reaction, 5-methylamino-5H-dibenzo[a,d]cycloheptene was cyclized upon treatment with bromine and aqueous base (Dygos, J. H. J. Heterocycl. Chem. 1976, 13, 1355).
7. 3) § 7.61-7.27 (m, 8H, ArH), 5.72 (d, J = 5.5 Hz, 1H), 4.87 (d,./ = 5.5 Hz, 1H), 3.47 (br s, 1H, NH).
8. 7. Thompson, W. J.; Anderson, P. S.; Britcher, S. F.; Lyle, T. A.; Thies, J. E.; Magill, C. A.; Varga, S. L.; Schwering, J. E.; Lyle, P. A.; Christy, M. E.; Evans, B. E.; Colton, C. D.; Holloway, M. K.; Springer, J. P.; Hirshfield, J. M.; Ball, R. G.; Amato, J. S.; Larsen, R. D.; Wong, E. H. F.; Kemp, J. A.; Tricklebank, M. D.; Singh, L.; Oles, R.; Priestly, T.; Marshall, G. R.; Knight, A. R.; Middlemiss, D. N.; Woodruff, G. N.; Iversen, L. L. J. Med. Chem. 1990, 33, 789, and references cited therein.
9. 8. Reduction of alkyl halides using borohydride or cyanoborohydride reagents in polar aprotic solvents such as DMSO or HMPA has been reported by Hutchins, R. O.; Kandasamy, D.; Dux III, F.; Maryanoff, C. A.; Rotstein, D.; Goldsmith, B.; Burgoyne, W.; Cistone, F.; Dalessandro, J.; Puglis, J. J. Org. Chem. 1978, 43, 2259.
10. 9. The corresponding 5-methyl aziridine has been synthesized by a different route by Larsen, R. D.; Davis, P.; Corley, E. G.; Reider, P. J.; Lamanec, T. R.; Grabowski, E. J. J. J. Org. Chem. 1990, 55, 299.
11. 1H NMR spectrum of the other intermediate is consistent with an 11β-substituted 10,11 -dihydro-5H-dibenzo[a,d]cyciohepten-5,10-imine. However, the structure of this intermediate has not been determined.
12. 11. Gonzalez, J.; Carroll, F. I., unpublished results.
13. 12. Snyder, H. R.; Elston, C. T. J. Am. Chem. Soc. 1954, 76, 3039.
14. 13. Hall, J. H.; Gisler, M. J. Org. Chem. 1976, 41, 3769.
15. 14. Lamanec, T. R.; Bender, D. R.; DeMarco, A. M.; Karady, S.; Reamer, R. A.; Weinstock, L. M. J. Org. Chem. 1988, 53, 1768.