A regioselective approach to trisubstituted 2 (or 6)-arylaminopyrimidine-5- carbaldehydes and their application in the synthesis of structurally and electronically unique G∧C base precursors

Journal of Organic Chemistry

Volumn 73, Issue 3, 2008, Pages 931-939

  Beingessner, Rachel L ^a   Deng, Bo Liang ^b   Fanwick, Phillip E ^c   Fenniri, Hicham ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b NEKTAR THERAPEUTICS   (United States)

^c PURDUE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHASE TRANSFER CATALYSIS; REGIOSELECTIVE SYNTHESIS; TRICHLOROPYRIMIDINE;

AMINES; NUCLEOPHILES; PHASE TRANSITIONS; REGIOSELECTIVITY; SYNTHESIS (CHEMICAL);

ALDEHYDES;

ALDEHYDE DERIVATIVE; AMINOPYRIMIDINE 5 CARBALDEHYDE DERIVATIVE; ANILINE; AROMATIC AMINE; BICYCLO COMPOUND; FUNCTIONAL GROUP; FUSED HETEROCYCLIC RINGS; METHYLAMINE; NUCLEOPHILE; OXIDE; PYRIMIDINE DERIVATIVE; TOLUENE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHEMICAL MODIFICATION; CHEMICAL REACTION; CHEMICAL STRUCTURE; DEPROTECTION REACTION; NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION; PHASE TRANSFER CATALYSIS; REGIOSELECTIVITY; SUBSTITUTION REACTION; SUZUKI REACTION; SYNTHESIS;

ALCOHOLS; ALDEHYDES; AMINES; CHLORINE COMPOUNDS; CROSS-LINKING REAGENTS; CYCLIZATION; ELECTRONS; HYDROLYSIS; IMINES; METHYLATION; MOLECULAR STRUCTURE; NITRILES; PYRIMIDINES; STEREOISOMERISM;

EID: 38849118431     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo7021422     Document Type: Article

References (73)

1. For reviews on pyrimidines see: (a) Brown, D. J.; Evans, R. F.; Cowden, W. B.; Fenn, M. D. The Pyrimidines; Wiley: New York, 1994.
2. (b) Brown, D. J. The Chemistry of Heterocyclic Compounds; Vol. 16, The Pyrimidines; Weissberger, A., Ed.; Wiley-Interscience: New York, 1970.
3. (c) Hurst, D. T. An Introduction to the Chemistry and Biochemistry of Pyrimidines, Purines and Pteridines; Wiley: Chichester, UK, 1980.
4. van Herrewege, Y.; Vanham, G.; Michiels, J.; Fransen, K.; Kestens, L.; Andries, K.; Janssen, P.; Lewi, P. Antimicrob. Agents Chemother. 2004, 48, 3684-3689.
5. (a) Sammond, D. M.; Nailor, K. E.; Veal, J. M.; Nolte, R. T.; Wang, L.; Knick, V. B.; Rudolph, S. K.; Truesdale, A. T.; Nartey, E. N.; Stafford, J. A.; Kumar, R.; Cheung, M. Bioorg. Med. Chem. Lett. 2005, 15, 3519-3523.
6. (b) Dev, I. K.; Dornsife, R. E.; Hopper, T. M.; Onori, J. A.; Miller, C. G.; Harrington, L. E.; Dold, K. M.; Mullin, R. J.; Johnson, J. H.; Crosby, R. M.; Truesdale, A. T.; Epperly, A. H.; Hinkle, K. W.; Cheung, M.; Stafford, J. A.; Luttrell, D. K.; Kumar, R. Br. J. Cancer 2004, 91, 1391-1398.
7. Geisen, K. U.S. Patent 6,156,755, 2000.
8. Cai, S. X.; Drewe, J. A.; Nguyen, B.; Reddy, P. S.; Pervin, A. PCT Int. Appl WO 02/47690 A1, 2002
9. (a) Mascal, M.; Hext, N. M.; Warmuth, R.; Moore, M. H.; Turkenburg, J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 2204-2206.
10. (b) Marsh, A.; Silvestri, M.; Lehn, J.-M. Chem. Commun. 1996, 1527-1528.
11. (c) Whitesides, G. M.; Simanek, E. E.; Mathias, J. P.; Seto, C. T.; Chin, D. N.; Mammen, M.; Gordon, D. M. Acc. Chem. Res. 1995, 28, 37-44.
12. (d) Kolotuchin, S. V.; Zimmerman, S. C. J. Am. Chem. Soc. 1998, 120, 9092-9094.
13. (e) Meléndez, R. E.; Hamilton, A. D. Top. Curr. Chem. 1998, 198, 97-129.
14. (f) Prins, L. J.; Reinhoudt, D. N.; Timmerman, P. Angew. Chem., Int. Ed. 2001, 40, 2382-2426.
15. (g) Stoddart, J. F.; Tseng, H.-R. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4797-4800.
16. (h) Lehn, J.-M. NATO ASI Series, E. Appl. Sci. 1996, 320, 511-524.
17. (i) MacGillivray, L. R.; Atwood, J. L. Angew. Chem., Int. Ed. 1999, 38, 1018-1033.
18. (j) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek, J., Jr. Angew. Chem., Int. Ed. 2002, 41, 1488-1508.
19. (k) Leininger, S.; Olenyuk, B.; Stang, P. J. Chem. Rev. 2000, 100, 853-908.
20. (l) Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M.; Sommerdijk, N. A. J. M. Chem. Rev. 2001, 101, 4039-4070.
21. (m) Reinhoudt, D. N.; Crego-Calama, M. Science 2002, 295, 2403-2407.
22. (n) Mascal, M. Contemporary Org. Synth. 1994, 1, 31-46.
23. (o) Müller, A.; Reuter, H.; Dillinger, S. Angew. Chem., Int. Ed. 1995, 34, 2328-2361.
24. (p) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem. Rev. 2001, 101, 3893-4011.
25. (q) Lawrence, D. S.; Jiang, T.; Levett, M. Chem. Rev. 1995, 95, 2229-2260.
26. (r) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem. Rev. 2001, 101, 4071-4097.
27. (a) Fenniri, H.; Deng, B.-L.; Ribbe, A. E. J. Am. Chem. Soc. 2002, 124, 11064-11072.
28. (b) Fenniri, H.; Deng, B.-L.; Ribbe, A. E.; Hallenga, K.; Jacob, J.; Thiyagarajan, P. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 6487-6492.
29. (c) Fenniri, H.; Mathivanan, P.; Vidale, K. L.; Sherman, D. M.; Hallenga, K.; Wood, K. V.; Stowell, J. G. J. Am. Chem. Soc. 2001, 123, 3854-3855.
30. (d) Moralez, J. G.; Raez, J.; Yamazaki, T.; Motkuri, R. K.; Kovalenko, A.; Fenniri, H. J. Am. Chem. Soc. 2005, 127, 8307-8309.
31. (e) Raez, J.; Moralez, J. G.; Fenniri, H. J. Am. Chem. Soc. 2004, 126, 16298-16299.
32. (f) Chun, A. L.; Moralez, J. G.; Webster, T. J.; Fenniri, H. Biomaterials 2005, 26, 7304-7309.
33. (g) Johnson, R. S; Yamazaki, T.; Kovalenko, A.; Fenniri, H. J. Am. Chem. Soc. 2007, 129, 5735-5743.
34. For representative examples see: (a) Byth, K. F.; Culshaw, J. D.; Green, S.; Oakes, S. E.; Thomas, A. P. Bioorg. Med. Chem. Lett. 2004, 14, 2245-2248.
35. (b) Kohra, S.; Tominaga, Y.; Hosomi, A. J. Heterocycl. Chem. 1988, 25, 959-968.
36. (c) Kidwai, M.; Saxena, S.; Rastogi, S.; Venkataramanan, R. Curr. Med. Chem.,: Anti-Infective. Agents 2003, 2, 269-286.
37. (d) Muller, T. J. J.; Braun, R.; Ansorge, M. Org. Lett. 2000, 2, 1967-1970.
38. (e) Gerns, F. R.; Perrotta, A.; Hitchings, G. H. J. Med. Chem. 1966, 9, 108-115.
39. (a) Johns, B. A.; Gudmundsson, K. S.; Turner, E. M.; Allen, S. H.; Samano, V. A.; Ray, J. A.; Freeman, G. A.; Boyd, F. L., Jr.; Sexton, C. J.; Selleseth, D. W.; Creech, K. L.; Moniri, K. R. Bioorg. Med. Chem. 2005, 13, 2397-2412.
40. (b) Ringom, R.; Axen, E.; Uppenberg, J.; Lundbäck, T.; Rondahl, L.; Barf, T. Bioorg. Med. Chem. Lett. 2004, 14, 4449-4452.
41. (c) Byth, K. F.; Culshaw, J. D.; Green S.; Oakes, S. E.; Thomas, A. P. Bioorg. Med. Chem. Lett. 2004, 14, 2245-2248.
42. (d) Verma, S.; Nagarathnam, D.; Shao, J.; Zhang, L.; Zhao, J.; Wang, Y.; Li, T.; Mull, E.; Enyedy, I.; Wang, C.; Zhu, Q.; Altieri, M.; Jordan, J.; Dang, T.; Reddy. S. Bioorg. Med. Chem. Lett. 2005, 15, 1973-1978.
43. (e) Yan, H.; Boehm, J. C.; Jin, Q.; Kasparec, J.; Li, H.; Zhu, C.; Widdowson, K. L.; Callahan, J. F.; Wan, Z. Tetrahedron Lett. 2007, 48, 1205-1207.
44. (f) Font, D.; Heras, M.; Villalgordo, J. M. J. Comb. Chem. 2003, 5, 311-321.
45. (g) Chhabria, M. T.; Bhatt, H. G.; Raval, H. G.; Oza, P. M. Bioorg. Med. Chem. Lett. 2007, 17, 1022-1024.
46. (h) Mesguiche, V.; Parsons, R. J.; Arris, C. E.; Bentley, J.; Boyle, F. T.; Curtin, N. J.; Davies, T. G.; Endicott, J. A.; Gibson, A. E.; Golding, B. T.; Griffin, R. J.; Jewsbury, P.; Johnson, L. N.; Newell, D. R.; Noble, M. E. M.; Wang, L. Z.; Hardcastle, I. R. Bioorg. Med. Chem. Lett. 2003, 13, 217-222.
47. O'Brien, D. E.; Weinstock, L. T.; Cheng, C. C. J. Med. Chem. 1968, 11, 387-388.
48. Yoneda, F.; Sakuma, Y.; Mizumoto, S.; Ito, R. J. Chem. Soc., Perkin Trans. 1 1976, 1805-1808.
49. (a) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis: Fundamentals, Applications, and Industrial Perspectives; Chapman and Hall: New York, 1994.
50. (b) Dehmlow, E. V.; Dehmlow, S. S. Phase-Transfer Catalysis, 3rd ed.; VCH: Weinheim, Germany, 1993.
51. (c) Shioiri, T. Chiral Phase-Transfer Catalysis. In Handbook of Phase-Transfer Catalysis; Sasson, Y., Neumann, R., Eds.; Blackie: London, UK, 1997, Chapter 14.
52. For examples see: (a) Ye, C.; Gao, H.; Boatz, J. A.; Drake, G. W.; Twamley, B.; Shreeve, J. M. Angew. Chem., Int. Ed. 2006, 45, 7262-7265.
53. (b) Vlasov, V. M. Russ. J. Org. Chem. 1998, 34, 1310-1321.
54. (c) Stuart, A. M.; Vidal, J. A. J. Org. Chem. 2007, 72, 3735-3740.
55. (d) Calafat, S. V.; Durantini, E. N.; Chiacchiera, S. M.; Silber, J. J. J. Org. Chem. 2005, 70, 4659-4666.
56. (e) Desai, N. D.; Shah, R. D. Synthesis 2006, 19, 3275-3279.
57. (f) Feldman, D.; Segal-Lew, D.; Rabinovitz, M. J. Org. Chem. 1991, 56, 7350-7354.
58. (g) Singh, P.; Arora, G. Tetrahedron, 1988, 44, 2625-2632.
59. (h) Landini, D.; Montanari, F.; Rolla, F. J. Org. Chem. 1983, 48, 604-605.
60. (i) Landini, D.; Maia, A.; Montanari, F. J. Chem. Soc., Perkin Trans. 2 1983, 461-466.
61. (j) Neumann, R.; Sasson, Y. Tetrahedron 1983, 39, 3437-3440.
62. 3 as a base in PTC see: (a) Kiser, E. J. PCT Int. Appl WO 136910, A1, 2006.
63. (b) Perlman, N.; Gilboa, E. PTC INT. Appl. WO 044648, A1, 2006.
64. (c) Mafatlal, K. B.; Ambalal, M. I.; Chandrakant, S. M.; Kashyapbhai, P. K.; Prabhakar, D. S.; Ravi, P.; Jagdish, D. S.; Raman, J. V. PCT Int. Appl WO 114676, A2, 2006.
65. NAr reaction since a negative charge can be delocalized on the two nitrogen atoms in the ring. Position 4, alternatively, is less reactive since there is little directing effect from the aldehyde group as it is already hydrogen bonded to the amine hydrogen at position 6.
66. The disubstituted product, 4-chloro-2,6-bis(methylamino)pyrimidine-5- carbaldehyde, was isolated in 76% yield.
67. Henderson, W. A., Jr.; Schultz, C. J. J. Org. Chem. 1962, 27, 4643-4646.
68. 1H NMR and ESI-mass spectral data strongly suggest the bicyclic product analogous to 24a-c.
69. For reviews see: (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147-168.
70. (b) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 15, 2419-2440.
71. (c) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
72. (d) Suzuki, A. Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998; Chapter 2.
73. Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-4028.