Синтез энантиомерно чистых производных имидазопиридина и пиридохиноксалина, содержащих хиральный заместитель при атоме азота
Диссертация
Показано, что производные пиридоимидазопиразин-6,8(7Я, 9//)-дионов, вследствие кето-енольной таутомерии, не могут быть выделены в энантиомерно чистом виде, для подтверждения данной теории с высокой энантиомерной чистотой синтезирован (98)-7-(2,4-диметоксибензил)-9-метил-8,9-дигидропиридоимидазопиразин-6(7//)-он, не способный к таутомерным превращениям. Таким образом, исходя из всего выше… Читать ещё >
Содержание
- 1. Введение
- 2. Методы получения производных имидазо[4,5−6]пиридинов и пиридо[2,3- ^ 6]пиразин-2,3-Дионов (Литературный обзор)
- 2. 1. Синтез производных имидазо[4,5-&]пиридина б
- 2. 2. Синтез производных пиридо[2,3−6]пиразин-2,3-диона
- 3. Синтез новых конденсированных гетероциклических соединений, содержащих хиральный заместитель при атоме азота на основе энантиомерно 13 чистых 1!-алкил пиридин-2,3-Диаминов (обсуждение результатов)
- 3. 1. Синтез производных 1,2,3,4-тетрагидро[2,3-Ь]пиразин-2,3-Диона с хиральным ^ заместителем при атоме азота
- 3. 2. Функционализация производных 1,2,3,4-тетрагидро[2,3−6]пиразин-2,3-Диона с хиральным заместителем при атоме азота. Арилирование и 21 гетарилирование пиразинового фрагмента
- 3. 3. Определение оптической чистоты полученных 2-арилпиридо[2,3−6]пиразиндионов
- 3. 4. Синтез производных имидазо[4,5−6]пиридина с хиральным заместителем при атоме азота
- 3. 5. Превращения имидазо[4,5−6]пиридинов в производные пиперазина
- 4. Экспериментальная часть
- 5. Выводы
Список литературы
- Dubey Р.К., Kumar R.V., Naidu A., Kulkarni S.M. A Review on the Biological Activity of Imidazo (4,5-b) Pyridines and Related Compounds. // Asian J. Chem., 2002, 14, 1129.
- Von Bebenburg W. Aza-benzimidazoles and process for their production. // US Pat., 3 819 640, 1974.
- Robinson M.M., Finch N. Imidazo (4,5-?)pyridines. // US Pat., 3 719 683,1973.
- Lesher G.Y., Brundage R.P., Opalka C.J., Page D.F. Imidazo (4,5-o)pyridine Derivatives Useful as Cardiotonics and Preparation. // Fr. Pat., 2 478 637, Chem. Abstr., 1982, 96, 85 551.
- Kueznski L., Mrozikiewiez A., Poreba K. Synthesis and biological properties of imidazo-4,5−6.-pyridine derivatives. // Pol. J. Pharmacol. Pharm., 1982, 34, 229.
- Bianchi M., Butti M., Rossi A., Barzaghi F., Marcaria V. Compounds with antiulcer and antisecretory activity. Ill: N-substituted imidazolones condensed with nitrogen-containing heteroaromatic rings. // Eur. J. Med. Chem. Chim. Ther., 1983, 18, 501.
- Babbar O.P., Chowdhur B.L. Further studies on antiviral effect of 3-beta-D-ribofuranosyl imidazo (6)pyridine on Ranikhet disease virus. // J. Sei. Ind. Res., 1962, 21c, 312.
- Roos K.B., Salemink C.A. Deazapurine derivatives. VII: Synthesis of substituted imidazo- and triazolo-pyridines. // Ree. Trav. Chim., 1971, 90, 1166.
- Montgomery J.A., Hewson K. 3-Deaza-6-methylthiopurine Ribonucleoside. // J. Med. Chem., 1966, 9, 105.
- Vaughn J.R. Imidazopyridines. // US Pat., 2 637 731, 1953.
- Rochling H.F.M., Buchel K.H., Korte W.A.G.K. Certain substituted imidazo (4,5-b or c) pyridines. // US Pat., 3 459 759, 1969.
- Doherty G.O.P. Rodenticidal imidazo-pyridines. // US Pat., 3 941 882, 1996.
- Khut L., Turski A. Quinoxalindione derivatives, their preparation and their use in drugs.//W09425469, 1994.
- Hansen PI.C., Watjen F. Imidazoquinoxaline compounds and their preparation and use. // US Pat., 4 968 682,1988.
- Weber M., Bartsch IT., Erker Т. Synthesis of a New Series of Imidazo-l, 5-a.pyrido[2,3-e]pyrazines as Potential Ligands for the GABA Receptor Complex. // Monatsh. Chem., 2002, 133, 653.
- Dudash J., Zhang Y., Moore J.В., Look R., Liang Y., Beavers M.P., Conway B.R., Rybczynski P.J., Demarest K.T. Synthesis and evaluation of 3-anilino-quinoxalinones as glycogen phosphorylase inhibitors. // Bioorg. Med. Chem. Lett., 2005, 15, 4790.
- Zhang IT., Feng D., Chen L., Long Y. Discovery of novel (S)-a-phenyl-c-amino butanamide containing CCR5 antagonists via functionality inversion approach. // Bioorg. Med. Chem. Lett., 2010, 20, 2219.
- Brown D.L., Owen D.R., Phillips C., Palmer M.J., Bell A.S., Freskos J.N., Fobjan Y.M., Walker J.K., Hughes R.C., Jacobsen E.J., Tollefson M.B., Brown D.G., Mischke B.V., Molyneaux J.M. Pyridopyrazinones as PDE-5 inhibitors. // W02007/20 521, 2007.
- Бухряков К.В., Куркин A.B., Юровская М. А. Методы получения производных имидазо4,5-Ь.пиридинов (обзор). // ХГС, 2011, 5, 646.
- Bernstein J., Stearns B., Shaw E., Lott W.A. Derivatives of 2,6-Diaminopyridine. HJ. Am. Chem. Soc., 1947, 69, 1151.
- Albert A., Barlin G.B. Triazanaphthalenes. Part IV. Covalent Hydration in 1,4,5-Triazanaphthalenes. II Journal of the Chemical Society, 1963, 5737.
- Shishikura J., Inami H., Sakamoto S., Tsukamoto S., Sasamata M., Okada M., Fujii M. 1,2,3,4-tetrahydroquinoxalinedione derivative. // US Pat. 6 096 743,1990.
- Micheli F., Cugola A., Donati D., Missio A., Pecunioso A., Reggiani A., Tarzia G. 2,3-Dihydro-6,7-dichloro-pyrido2,3-Z>.pyrazine-8-oxide as selective glycine antagonist with in vivo activity. // Bioorg. Med. Chem., 1997, 5, 2129.
- Kuethe J.T., Wong A., Davies l.W. Synthesis of Disubstituted Imidazo4,5-?>.pyridin-2-ones. II J. Org. Chem., 2004, 69, 7752.
- Collins P.A., McFarlane M.D., Mackie R.K., Smith D.M. o-Nitroaniline Derivatives 13 reactions of N-(o-nitroaryl)sarcosine esters with bases. // Tetrahedron, 1992, 48, 7887.
- McFarlane M.D., Smith D.M. A new route to N-hydroxyquinoxaline-2,3-diones and some aza-analogues. // Tetrahedron Lett., 1987, 28, 6363.
- VanDongen, A. M. Biology of the NMDA receptor. CRC Press: Boca Raton, 2009.
- Botton G., Valeur E., Kergoat M., Charon C., Elbawab S. Pyrazinone derivatives as insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes. // W02009/109 341, 2009.
- Beavers M.P., Dudash J., Zhang Y. Quinoxalinones. // U.S. Patent 148 586, 2005.
- Greene T.W., Wuts P.G. Protective Groups in Organic Synthesis, 2nd Ed.- John Wiley & Sons, New York, 1991.
- Roeske R. Preparation of /-Butyl Esters of Free Amino Acids. // J. Org. Chem., 1963,28, 1251.
- Stanton M.G., Gagne M.R. A Mild Protocol for the Conversion of Simple Esters to tert-Butyl Esters. II J. Org. Chem. 1997, 62, 8240.
- Hallock Y.F., Manfredi K.P., Blunt J.W., Francois G" Boyd M.R., Korupensamines A.D. Novel Antimalarial Alkaloids from Ancistrocladus korupensis. II J. Org. Chem., 1994, 59, 6349.
- Watanabe T., Kamikawa K., Uemura M. Synthesis of both axially chiral biaryls by cross-coupling of (arene)chromium complexes with naphthylboronic acids and subsequent axial isomerization. // Tetrahedron Lett., 1995, 36, 6695.
- Bringmann G., Walter R., Weirich R., The directed synthesis of biaryl compounds: Modern concepts and strategies. // Angew. Chem. Int. Ed. Engl., 1990, 29, 977.
- Bahl A., Grahn W., Stadler S" Feiner F" Bourhill G" Reisner A., Jones P.G. Novel, Blue-Transparent Frequency Doublers Based on 1,8-Di (hetero)arylnaphthalenes. 11 Angew. Chem. Int. Ed. Engl., 1995, 34, 1485.
- Miyaura N., Yamada K., Suzuki A. A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkvnyl halides. // Tetrahedron Lett. 1979, 3437.
- Stanforth S.P., Catalytic cross-coupling reactions in biaryl synthesis. // Tetrahedron, 1998, 54, 263. .
- Suzuki A. Synthetic studies via the cross-coupling reaction of organoboron derivatives with organic halides. 11 Pure Appl. Chem., 1991, 63, 419.
- Baba S., Negishi E. A novel stereospecific alkenyl-alkenyl cross-coupling by a palladium- or nickel-catalyzed reaction of alkenylalanes with alkenyl halides. // J. Am. Chem. Soe., 1976, 98, 6729.
- Dai C., Fu C. The First General Method for Palladium-Catalyzed Negishi Cross-Coupling of Aryl and Vinyl Chlorides: Use of Commercially Available Pd (P (7-Bu)3)2 as a Catalyst. // J. Am. Chem. Soc., 2001, 123, 2719.
- Tamao K., Sumitani K., Kumada M: Selective carbon-carbon bond formation by cross-coupling of Grignard reagents with organic halides. Catalysis by nickel-phosphine complexes. // J. Am. Chem. Soe., 1972, 94, 4374.
- Herrmann W.A., Bohm V.P.W., Reisinger C. Application of palladacycles in Heck type reactions. II J. Organomet. Chem., 1999, 576, 23.
- Gouda K., Hagiwara E., Hatanaka Y., Hiyama T. Cross-Coupling Reactions of Aryl Chlorides with Organochlorosilanes: Highly Effective Methods for Arylation or Alkenylation of Aryl Chlorides. II J. Org. Chem. 1996, 61, 7232.
- Mowery M.E., DeShong P. Improvements in cross coupling reactions of hypervalent siloxane derivatives. // Org. Lett., 1999, 1, 2137.
- Stille J.K. Palladium catalyzed coupling of organotin reagents with organic electrophiles. // Pure Appl. Chem. 1985, 57, 1771.
- Stille J.K. The Palladium-Catalyzed Cross-Coupling Reactions of Organotin Reagents with Organic Electrophiles. // Angew. Chem., Int. Ed., 1986, 25, 508.
- Farina V., Krishnamurthy V., Scott W. The Stille reaction. II J. Org. React., 1997, 50, 1.
- Cherkaoui O., Essassi E.M., Zniber R. Heterocyclisation des 2-aminoalkyl (et aryl) benzimidazoles en catalyse par transfert de phase. // Bull. soc. chim. Fr., 1991, 128,255.
- Matrick H., Day A.R. Syntheses of l, 2,3,4-Tetrahydropyrazinol, 2-ajbenzimidazoles and 3-Carbethoxy-3-phenyl-1,2,3,4-tetrahydropyrido[ 1,2-ajbenzimidazole. // J. Org. Chem., 1961, 26, 1511.
- Carey F.A., Sundberg R.J. Advanced Organic Chemistry. Part B. Reactions and Synthesis, 4th Ed. Kluwer Academic/Plenum Publishers, New York, 2000, 177.
- Deana A.A., Solms S.J., Graham S.L., Smith R.L. Inhibitors of farnesyl protein transferase. // U.S. Patent 5 352 705, 1994.
- Sheldrick G.M. SHELXS-97, Program for Solution of Crystal Structures from Diffraction Data, Universitat Gottingen, Germany, 1997.
- Sheldrick G.M. SHELXL-97, Program for Crystal Structure Refinement, Universitat Gottingen, Germany, 1997.