An intramolecular sulfoxide alkylation-elimination approach to the [1,2,3]triazolo[1,5-a]pyrimidine ring system

Synlett

Volumn , Issue 5, 2001, Pages 712-714

  Gibson, Karl R ^a   Thomas, Steven R ^a   Rowley, Michael ^a  

^a NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

Author keywords

Alkylations; Cyclisations; Eliminations; Rearrangements; Sulfoxides

Indexed keywords

1,2,3 TRIAZOLE[1,5 A]PYRIMIDINE; PYRIMIDINE DERIVATIVE; SULFOXIDE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; STRUCTURE ANALYSIS;

EID: 0035038380     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2001-13354     Document Type: Article

References (15)

1. McKernan, R. M.; Rosahl, T. W.; Reynolds, D. S.; Sur, C.; Wafford, K. A.; Atack, J. R.; Farrar, S.; Myers, J.; Cook, G.; Ferris, P.; Garrett, L.; Bristow, L.; Marshall, G.; Macaulay, A.; Brown, N.; Howell, O.; Moore, K. W.; Carling, R. W.; Street, L. J.; Castro, J. L.; Ragan, C. I.; Dawson, G. R.; Whiting, P. J. Nat. Neurosci. 2000, 3, 587.
2. Broughton, H. B.; Castro Pineiro, J. L.; Collins, I. J.; Gibson, K. R.; Rowley, M.; Street, L. J. WO 99/65907 (Merck Sharp and Dohme Ltd, UK)
3. For previous work on less substituted [1,2,3]triazolo[1,5-a]pyrimidines see Sutherland, D. R.; Tennant, G.; Vevers, R. J. S. J. Chem. Soc. Perkin Trans. 1 1973, 943 and Sutherland, D. R.; Tennant, G. J. Chem. Soc. Chem. Commun. 1969, 1070.
4. For previous work on less substituted [1,2,3]triazolo[1,5-a]pyrimidines see Sutherland, D. R.; Tennant, G.; Vevers, R. J. S. J. Chem. Soc. Perkin Trans. 1 1973, 943 and Sutherland, D. R.; Tennant, G. J. Chem. Soc. Chem. Commun. 1969, 1070.
5. Trost, B. M.; Pearson, W. H. J. Am. Chem. Soc. 1981, 103, 2483. This azide is commercially available from Aldrich.
6. Cottrell, I. F.; Hands, D.; Houghton, P. G.; Humphrey, G. R.; Wright, S. H. B. J. Heterocycl. Chem. 1991, 28, 301. The regiochemistry of the cyloaddition was confirmed by the observation of a nOe between the methylene protons adjacent to sulphur and the protons of the amino group.
7. Bordwell, F. G.; Pitt, B. M. J. Am. Chem. Soc. 1955, 77, 572.
8. α-Bromo-cyclopentylacetyl chloride and α-bromo-cyclobutyl chloride prepared according to standard literature procedure: Harpp, D. N.; Bao, L. Q.; Coyle, C.; Gleason, J. G.; Horovitch, S. Org. Synth. 1988, VI, 190. In the course of acylation the bromine was displaced by chloride ion, leading to isolation of the chlorinated products.
9. For 2 recent reveiws see a) L'Abbé, G. J. Heterocyclic Chem. 1984, 21, 627.
10. b) Fan, W-Q; Katritzky, A. R. in Comprehensive Heterocyclic Chemistry II, Vol 4; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Eds; Pergamon: London, 1996, p 30.
11. The final isomer ratio is solvent dependent, heating in either acetonitrile or methanol affords a 1:10 ratio of 6:7. The product structures were assigned by analysis of a NOESY spectrum of the mixture of isomers. In 6 the pyrimidinone C-H shows an nOe only to the unsubstituted phenyl ring. In 7 the pyrimidinone C-H shows this nOe and an additional nOe to the exchangeable NH signal.
12. Lieber, E.; Rao, N. R.; Chao, T. S. J. Am. Chem. Soc. 1957, 79, 5962.
13. a) Comins, D. L.; Jianhua, G. Tetrahedron Lett. 1994, 35, 2819.
14. b) Kim, T. H.; Rappoport, H. J. Org. Chem. 1990, 55, 3699.
15. 3 (128 mg, 0.49 mmol) and 2-methyl-2/H-[1,2,4]triazol-3-yl)-methanol (62 mg, 0.49 mmol), were suspended at room temperature in dry THF (1.5 mL).