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Volumn 73, Issue 9, 2008, Pages 3508-3515

Practical synthesis of a vanilloid receptor-1 antagonist

Author keywords

[No Author keywords available]

Indexed keywords

MEDICAL APPLICATIONS; PATIENT TREATMENT; SYNTHESIS (CHEMICAL);

EID: 43449104720     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo8002216     Document Type: Article
Times cited : (37)

References (43)
  • 1
    • 2442642767 scopus 로고    scopus 로고
    • For a general overview see: a
    • For a general overview see: (a) Szallasi, A.; Appendino, G. J. Med. Chem. 2004, 47, 2717.
    • (2004) J. Med. Chem , vol.47 , pp. 2717
    • Szallasi, A.1    Appendino, G.2
  • 8
    • 43449132863 scopus 로고    scopus 로고
    • $424 for 25 g
    • $424 for 25 g.
  • 15
    • 43449090842 scopus 로고    scopus 로고
    • Identified by LC/MS analysis
    • Identified by LC/MS analysis.
  • 16
    • 43449089010 scopus 로고    scopus 로고
    • The intermediates in this proposed mechanism were not observed directly
    • The intermediates in this proposed mechanism were not observed directly.
  • 22
    • 43449120837 scopus 로고    scopus 로고
    • The following conditions were used: acetic anhydride, triethylamine, ethyl acetate, rt
    • The following conditions were used: acetic anhydride, triethylamine, ethyl acetate, rt.
  • 23
    • 0034605453 scopus 로고    scopus 로고
    • An enantioselective hydroamination for a leading reference see: Kawatsura, M, Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546. of 4-fluorostyrene with piperazine also appears feasible, but this option was not explored due to the relatively high price of the starting material
    • An enantioselective hydroamination (for a leading reference see: Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546. of 4-fluorostyrene with piperazine also appears feasible, but this option was not explored due to the relatively high price of the starting material.
  • 26
    • 0000627594 scopus 로고    scopus 로고
    • The obtained result was slightly inferior to results reported in the literature but no detailed optimization of this reaction was carried out at this point. For a reference see: Mathre, D. J, Thompson, A. S, Douglas, A. W, Hoogsten, K, Carroll, J. D, Gorley, E. Q, Grabowski, E. J. J. J. Org. Chem. 1993, 58, 2880
    • The obtained result was slightly inferior to results reported in the literature but no detailed optimization of this reaction was carried out at this point. For a reference see: Mathre, D. J.; Thompson, A. S.; Douglas, A. W.; Hoogsten, K.; Carroll, J. D.; Gorley, E. Q.; Grabowski, E. J. J. J. Org. Chem. 1993, 58, 2880.
  • 32
    • 0032568913 scopus 로고    scopus 로고
    • A ruthenium-catalyzed synthesis of piperazines was reported earlier (Abbenhuis, R. A. T. M.; Boersma, J.; van Koten, G. J. Org. Chem. 1998, 63, 4282. ) but elevated temperatures of 180 °C were necessary. The successful examples (yields 7-34%) were limited to cyclization with anilines. No products were obtained when primary aliphatic amines were used in the reaction.
    • A ruthenium-catalyzed synthesis of piperazines was reported earlier (Abbenhuis, R. A. T. M.; Boersma, J.; van Koten, G. J. Org. Chem. 1998, 63, 4282. ) but elevated temperatures of 180 °C were necessary. The successful examples (yields 7-34%) were limited to cyclization with anilines. No products were obtained when primary aliphatic amines were used in the reaction.
  • 42
    • 43449129334 scopus 로고    scopus 로고
    • The equimolar amounts for the starting materials are based on stoichiometry calculation not accounting for the potency of the starting materials. It was later discovered that the starting material 2 often only has potency wt/wt , of 90-95, which then de facto leads to use of excess 4,6-dichloropyrimidine in the coupling reaction
    • The equimolar amounts for the starting materials are based on stoichiometry calculation not accounting for the potency of the starting materials. It was later discovered that the starting material 2 often only has potency (wt/wt %) of 90-95%, which then de facto leads to use of excess 4,6-dichloropyrimidine in the coupling reaction.
  • 43
    • 43449096514 scopus 로고    scopus 로고
    • An additional suspension in ethanol/water, followed by filtration was needed to reduce the content of DMF in the API ∼4000 ppm in the crude material
    • An additional suspension in ethanol/water, followed by filtration was needed to reduce the content of DMF in the API (∼4000 ppm in the crude material).


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.