Abstract
N-Boc-protected 8-azaspiro[bicyclo[3.2.1]octane-3,2′-oxirane] reacted with primary aliphatic amines through opening of the epoxide ring with formation of the corresponding amino alcohols which were converted into N-chloroacetyl derivatives. The latter underwent cyclization to N-Boc-protected 4′-alkyl-8-azaspiro[bicyclo[3.2.1]octane-3,2′-morpholin]-5′-ones by the action of sodium hydride in DMF, and subsequent treatment with hydrogen chloride in ethyl acetate afforded 8-azaspiro[bicyclo[3.2.1]octane-3,2′-morpholin]-5′-one hydrochlorides.
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References
O’Hagan, D., Nat. Prod. Rep., 2000, vol. 17, p. 435.
Humphrey, A.J. and O’Hagan, D., Nat. Prod. Rep., 2001, vol. 18, p. 499.
De Simone, R., Margrucci, L., and De Feo, V., Pharmacologyonline, 2008, vol. 1, p. 70.
Grynkiewicz, G. and Gadzikowska, M., Pharm. Rep., 2008, vol. 60, p. 439.
Emmelkomp, J.M. and Rockstroh, J.K., Eur. J. Med. Res., 2007, vol. 12, p. 409.
Abel, S., Rock, D.J., and Vourvahis, M., Antivir. Ther., 2009, 14, 607.
Kostochka, L.M., Gan’shina, T.S., Mirzoyan, R.S., and Seredenin, S.B., Pharm. Chem. J., 2010, 44, no. 9, p. 472.
Carson, J.R., Coats, S.J., Codd, E.E., Dax, S.L., Lee, J., Martinez, R.P., Neilson, L.A., Pitis, P.M., and Zhang, S.-P., Bioorg. Med. Chem. Lett., 2004, vol. 14, p. 2109.
Riley, T.N. and Bagley, J., US Patent no. 4 432 983, 1984.
Macor, J.E., Gurley, D., Lanthorn, T., Loch, J., Mack, R.A., Mullen, G., Tran, O., Wright, N., and Gordon, J.C., Bioorg. Med. Chem. Lett., 2001, vol. 11, p. 319.
Cignarella, G., Villa, S., and Borlocco, D., Eur. J. Med. Chem., 1994, vol. 29, p. 115.
Ding, F., Dong, S., Frie, J., Gu, X., Jiang, J., Pasternak, A., Tang, Y., Wu, Z., Yu, X., and Suzuki, T., Int. Patent Appl. no. WO 015495, 2014.
Madaiah, M., Prashanth, M.K., Revanasiddappa, H.D., and Veeresh, B., Arch. Pharm. Life Sci., 2014, vol. 347, p. 370.
Basappa, C.S., Kumar, A., Swamy, S.N., Sugahara, K., and Rangappa, K.S., Bioorg. Med. Chem. Lett., 2009, vol. 17, p. 4928.
Moinet, C., Blais, C., Bubenic, M., Chan, C.K.L., Courchesne, M., Periera, O., Denis, R., Vaillancourt, L., and Yannopoulos, C.G., Int. Patent Appl. no. WO 143847, 2007.
Takamura, M., Yobu, K., Nirshi, T., Yanagisawa, H., Kanai, M., and Shibasaki, M., Synlett, 2003, p. 353.
Cochi, A., Metro, T.-X., Pardo, D.G., and Cossy, J., Org. Lett., 2010, vol. 12, p. 3693.
Metro, T.-X., Cochi, A., Pardo, G., and Cassy, J., J. Org. Chem., 2011, vol. 76, p. 2594.
Balsamo, A., Lapucci, A., Manera, C., Mortinelli, A., Nencetti, S., Orlandini, E., Calderone, V., Gannaccini, G., and Nieri, P., Eur. J. Med. Chem., 2002, vol. 37, p. 11.
Breschi, M.C., Calderone, V., Martelli, A., Minutolo, F., Rapposelli, S., Testoi, L., Tonelli, F., and Balsamo, A., J. Med. Chem., 2006, vol. 49, p. 7600.
Rafinski, Z., Kozakewicz, A., and Rafinska, K., Tetrahedron, 2014, vol. 70, p. 5739.
Schlienger, N., Thygesen, M.B., Pawlas, J., Badalassi, F., Lewinsky, R., Lund, B.W., and Olsson, R., US Patent Appl. Publ. no. 2006/0160845, 2006.
Schlienger, N., Lund, B., Pawlas, J., Badolassi, F., Bertozzi, F., Lewinsky, R., Feizic, A., Thygesen, M.B., Tabatabaei, A., Bradley, S.R., Gardell, L.R., Piu, F., and Olsson, R., J. Med. Chem., 2009, vol. 52, p. 7186.
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Original Russian Text © A.Yu. Mandzhulo, N.A. Mel’nichuk, V.N. Fetyukhin, M.V. Vovk, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 1, pp. 94–98.
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Mandzhulo, A.Y., Mel’nichuk, N.A., Fetyukhin, V.N. et al. Synthesis of 4′-alkyl-8-azaspiro[bicyclo[3.2.1]octane-3,2′-morpholin]-5′-ones. Russ J Org Chem 52, 87–91 (2016). https://doi.org/10.1134/S1070428016010164
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DOI: https://doi.org/10.1134/S1070428016010164