First safe and practical synthesis of 2-amino-8-hydroxyquinoline

Organic Process Research and Development

Volumn 8, Issue 4, 2004, Pages 663-665

  Storz, Thomas ^a   Marti, Roger ^b   Meier, Roland ^b   Nury, Patrice ^b   Roeder, Michael ^b   Zhang, Kesheng ^b  

^a AMGEN INC   (United States)

^b CarboGen AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 8 HYDROXYQUINOLINE; QUINOLINOL DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS;

EID: 4243200417     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op049944p     Document Type: Article

References (31)

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8. Kachin, S. V.; Golovina, A. P.; Runov, V. K.; Dziomko, V. M.; Krasavin, I. A.; Parusnikov, B. V. Zh. Anal. Khim. 1983, 38, 1390.
9. Bader, M. M.; Hamada, T.; Kakuta, A. J. Am. Chem. Soc. 1992, 114, 6475.
10. SciFinder/Beilstein Searches, Feb 2004.
11. Schneiderwirth, H. J. U.S. Patent 2,121,449, 1936.
12. Chichibabin, A. E.; Seide, O. A. J. Russ. Phys. Chem. Soc. 1914, 40, 1216.
13. Rudner, B. (W. R. Grace & Co.). U.S. Patent 2,892,841, 1956. Chloramine [chloramide] is a toxic, strong lachrymator/irritant. It is instable and highly explosive in the liquid state and currently not produced commercially in the United States; see: Dangerous Properties of Industrial Materials Report 1993, 13, 502. For a review of the chemical properties of chloramine, see: Sisler, H. H. J. Chem. Educ. 1983, 60, 1002.
14. Rudner, B. (W. R. Grace & Co.). U.S. Patent 2,892,841, 1956. Chloramine [chloramide] is a toxic, strong lachrymator/irritant. It is instable and highly explosive in the liquid state and currently not produced commercially in the United States; see: Dangerous Properties of Industrial Materials Report 1993, 13, 502. For a review of the chemical properties of chloramine, see: Sisler, H. H. J. Chem. Educ. 1983, 60, 1002.
15. Rudner, B. (W. R. Grace & Co.). U.S. Patent 2,892,841, 1956. Chloramine [chloramide] is a toxic, strong lachrymator/irritant. It is instable and highly explosive in the liquid state and currently not produced commercially in the United States; see: Dangerous Properties of Industrial Materials Report 1993, 13, 502. For a review of the chemical properties of chloramine, see: Sisler, H. H. J. Chem. Educ. 1983, 60, 1002.
16. Van Eijk, A. (ChemShop B.V., Netherlands) and Roeder, M. (CarboGen, Switzerland), unpublished results. The procedure was found to give multiple products, also in the case of the O-methylated derivative, and regularly led to tar formation. Moreover, a strongly exothermic behaviour was observed in the small-scale experiments that suggested a potential for thermal runaway on larger scale. Reports on the Chichibabin reaction of quinolines are scarce in the literature: the reaction mechanism appears to be complex and has been shown to lead to, among other products, 3,4-dihydroquinolines and the 4-amino regioisomer; see: Tondys, H.; Van der Plas, H. C.; Wozniak, M. J. Heterocycl. Chem. 1985, 22, 353 and Kametani, T.; Kigasawa, K.; Iwabuchi, Y.; Hayasaka, T. J. Heterocycl. Chem. 1965, 2, 330. Chichibabin reactions of hydroxyquinolines have not been reported to date (SciFinder/Beilstein Searches, Feb 2004).
17. Van Eijk, A. (ChemShop B.V., Netherlands) and Roeder, M. (CarboGen, Switzerland), unpublished results. The procedure was found to give multiple products, also in the case of the O-methylated derivative, and regularly led to tar formation. Moreover, a strongly exothermic behaviour was observed in the small-scale experiments that suggested a potential for thermal runaway on larger scale. Reports on the Chichibabin reaction of quinolines are scarce in the literature: the reaction mechanism appears to be complex and has been shown to lead to, among other products, 3,4-dihydroquinolines and the 4-amino regioisomer; see: Tondys, H.; Van der Plas, H. C.; Wozniak, M. J. Heterocycl. Chem. 1985, 22, 353 and Kametani, T.; Kigasawa, K.; Iwabuchi, Y.; Hayasaka, T. J. Heterocycl. Chem. 1965, 2, 330. Chichibabin reactions of hydroxyquinolines have not been reported to date (SciFinder/Beilstein Searches, Feb 2004).
18. Van Eijk, A. (ChemShop B.V., Netherlands) and Roeder, M. (CarboGen, Switzerland), unpublished results. The procedure was found to give multiple products, also in the case of the O-methylated derivative, and regularly led to tar formation. Moreover, a strongly exothermic behaviour was observed in the small-scale experiments that suggested a potential for thermal runaway on larger scale. Reports on the Chichibabin reaction of quinolines are scarce in the literature: the reaction mechanism appears to be complex and has been shown to lead to, among other products, 3,4-dihydroquinolines and the 4-amino regioisomer; see: Tondys, H.; Van der Plas, H. C.; Wozniak, M. J. Heterocycl. Chem. 1985, 22, 353 and Kametani, T.; Kigasawa, K.; Iwabuchi, Y.; Hayasaka, T. J. Heterocycl. Chem. 1965, 2, 330. Chichibabin reactions of hydroxyquinolines have not been reported to date (SciFinder/Beilstein Searches, Feb 2004).
19. See, for instance: Gershon, H.; Clarke, D. D. Monatsh. Chem. 1991, 122, 935. Note that transient O-protection of the 8-hydroxy group would be required for these approaches, thus lengthening the synthetic sequence by two steps.
20. In small quantities, 2-amino-8-hydroxyquinoline (1) can be purchased from Fluka/Sigma, but we were unable to identify a bulk manufacturer. 2,8-Dihydroxyquinoline as well as 2-chloro-8-hydroxy(or methoxy)quinoline are either very expensive or not commercially available beyond gram quantities. On the other hand, 8-hydroxyquinoline is offered on a multi-kilogram scale by a variety of bulk manufacturers (<$50/kg).
21. 3).
22. 3).
23. 3. A Lonza patent (EP 090173, 1983) claims the synthesis of 2-aminopyridines via decarboxylative α-amination of the corresponding 2-carboxypyridine-N-oxides. A prior reference (Wachi, K.; Terada, A. Chem. Pharm. Bull. 1980, 28, 465) mentions the use of a not readily accessible activating agent (4-chloro-2,2-dimethyl-2H-1,3-benzoxazine) for the conversion of pyridine-N-oxide to 2-aminopyridine.
24. 3. A Lonza patent (EP 090173, 1983) claims the synthesis of 2-aminopyridines via decarboxylative α-amination of the corresponding 2-carboxypyridine-N-oxides. A prior reference (Wachi, K.; Terada, A. Chem. Pharm. Bull. 1980, 28, 465) mentions the use of a not readily accessible activating agent (4-chloro-2,2-dimethyl-2H-1,3-benzoxazine) for the conversion of pyridine-N-oxide to 2-aminopyridine.
25. 2/2-methylpropanal (Dongre, R. S.; Rao, T. V.; Sharma, B. K.; Sain, B.; Bhatia, V. K. Synth. Commun. 2001, 31, 167).
26. 2/2-methylpropanal (Dongre, R. S.; Rao, T. V.; Sharma, B. K.; Sain, B.; Bhatia, V. K. Synth. Commun. 2001, 31, 167).
27. 2/2-methylpropanal (Dongre, R. S.; Rao, T. V.; Sharma, B. K.; Sain, B.; Bhatia, V. K. Synth. Commun. 2001, 31, 167).
28. 2/2-methylpropanal (Dongre, R. S.; Rao, T. V.; Sharma, B. K.; Sain, B.; Bhatia, V. K. Synth. Commun. 2001, 31, 167).
29. 2/2-methylpropanal (Dongre, R. S.; Rao, T. V.; Sharma, B. K.; Sain, B.; Bhatia, V. K. Synth. Commun. 2001, 31, 167).
30. The methylation of 3 has been reported (by dimethyl sulfate: [19b], by methyl mesylate: [19c]).
31. Pretsch, E., Seibl, J., Clerc, T., Simon, W., Eds. Spectral Data for Structure Determination of Organic Compounds, 2nd ed.; Springer-Verlag: Heidelberg, Germany, 1989; p H275.