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Volumn 15, Issue 1, 2011, Pages 31-43

Development of a practical synthesis of a pyrazolopyridinone-based p38 MAP kinase inhibitor

Author keywords

[No Author keywords available]

Indexed keywords

BUILDING BLOCKES; COMPLEX SOLIDS; EFFICIENT BUILDINGS; IN-SITU RAMAN SPECTROSCOPY; MAP KINASE; OPTIMAL CONTROLS; QUALITY ATTRIBUTES;

EID: 79251492035     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op100205s     Document Type: Article
Times cited : (20)

References (46)
  • 12
    • 79251515555 scopus 로고    scopus 로고
    • 18 may be observed via HPLC. Isolated 18 is a crystalline solid that slowly cyclizes to 6a in the solid state
    • 18 may be observed via HPLC. Isolated 18 is a crystalline solid that slowly cyclizes to 6a in the solid state.
  • 15
    • 79251515853 scopus 로고    scopus 로고
    • N -Acylation was also observed under the reaction conditions. N -Acylation of 5b imparted significant stabilization.
    • N -Acylation was also observed under the reaction conditions. N -Acylation of 5b imparted significant stabilization.
  • 17
    • 79251471209 scopus 로고    scopus 로고
    • note
    • During preparation of this manuscript, Norris et al. from Pfizer Process R&D reported a related application of the use of ascorbic acid in the reduction of diazonium salts
  • 19
    • 79251528647 scopus 로고    scopus 로고
    • Safety studies were carried out and showed 25 to be thermally stable under 160 °C.
    • Safety studies were carried out and showed 25 to be thermally stable under 160 °C.
  • 21
    • 79251529273 scopus 로고    scopus 로고
    • 2 afforded 4% of 29a.
    • 2 afforded 4% of 29a.
  • 22
    • 79251510958 scopus 로고    scopus 로고
    • All reactions achieved complete conversion with 19 h.
    • All reactions achieved complete conversion with 19 h.
  • 26
    • 0001478826 scopus 로고
    • Hunsdiecker and Related Reactions
    • Trost. B.M.; Fleming I., Eds.; Pergamon Press: Oxford
    • Crich, D. Hunsdiecker and Related Reactions. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 7, pp 717 - 734.
    • (1991) Comprehensive Organic Synthesis , vol.7 , pp. 717-734
    • Crich, D.1
  • 30
    • 79251496743 scopus 로고    scopus 로고
    • note
    • Attempts to observe 33 via react-IR failed due to its low concentration. Ionization under standard LC/MS conditions was also not successful. Related intermediates were previously observed by NMR spectroscopy in the decarboxylative bromination of cis -cinnamic acid. See ref 19b.
  • 31
    • 79251479805 scopus 로고    scopus 로고
    • For poorly soluble products, starting material may become entrained in the product, making it unavailable for reaction.
    • For poorly soluble products, starting material may become entrained in the product, making it unavailable for reaction.
  • 35
    • 79251528303 scopus 로고    scopus 로고
    • LiBr was critical to improve the N - vs O -selectivity.
    • LiBr was critical to improve the N-vs O -selectivity.
  • 36
    • 79251474122 scopus 로고    scopus 로고
    • note
    • 4 may be considered a privileged base for large-scale Suzuki couplings of this type as it is applicable to a wide range of substrates and does not present off-gassing issues upon neutralization.
  • 37
    • 79251513699 scopus 로고    scopus 로고
    • The major byproducts, 36 and 37 derived from 13 via deboronation and homocoupling, respectively, and 35 derived from 10b via dehalogenation, were fully characterized and their identities confirmed by synthesis.
    • The major byproducts, 36 and 37 derived from 13 via deboronation and homocoupling, respectively, and 35 derived from 10b via dehalogenation, were fully characterized and their identities confirmed by synthesis.
  • 41
    • 79251491119 scopus 로고    scopus 로고
    • Loading studies demonstrating that 0.1 mol % catalyst was sufficient to obtain both full conversion and acceptable reaction kinetics (<4 h).
    • Loading studies demonstrating that 0.1 mol % catalyst was sufficient to obtain both full conversion and acceptable reaction kinetics (<4 h).
  • 42
    • 79251528960 scopus 로고    scopus 로고
    • Isopropanol and water are typically miscible in all proportions; however, aqueous salt solutions are often immiscible with isopropanol.
    • Isopropanol and water are typically miscible in all proportions; however, aqueous salt solutions are often immiscible with isopropanol.
  • 43
    • 79251507069 scopus 로고    scopus 로고
    • note
    • The imidazolide intermediate was unstable under the HPLC conditions (0.1% TFA in acetonitrile/water); however, it could be quenched with benzylamine and then analyzed as the corresponding benzamide.
  • 44
    • 79251520045 scopus 로고    scopus 로고
    • note
    • The entrained imidazolide remained unreacted in isolated 4; however, it readily reacted with the solvent upon dissolution in the subsequent step.
  • 45
    • 79251488241 scopus 로고    scopus 로고
    • Modeling of the distillation was carried out using Dynochem modeling software.
    • Modeling of the distillation was carried out using Dynochem modeling software.
  • 46
    • 79251486431 scopus 로고    scopus 로고
    • note
    • This was determined by setting the target after distillation to 10 volumes of solvent composed of 4:1 ethanol/water. To reach this endpoint, Dynochem modeling of the azeotropic system showed a starting volume of 36.2 volumes composed of 6.7:1 ethanol/water to be required.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.