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Volumn 13, Issue 6, 2009, Pages 1169-1176

Preparation of saxagliptin, a novel DPP-IV inhibitor

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EID: 72449123195     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op900226j     Document Type: Article
Times cited : (74)

References (29)
  • 12
    • 72449162312 scopus 로고    scopus 로고
    • note
    • The combined mother liquor and cake washes had <1000 ppm of IPMS on scale.
  • 13
    • 72449149890 scopus 로고    scopus 로고
    • note
    • Lab-scale gas evolution studies showed that no significant gas was evolved until after ∼15% of the MSA was added and that, if the MSA addition was spread over 1 h or longer, ∼90% of the reaction would occur during the acid charge. This allowed a high level of control over the evolution of carbon dioxide and isobutylene.
  • 15
    • 72449170259 scopus 로고    scopus 로고
    • note
    • 3-DMF, 2-chloro-4,6-dimethoxy-1,3,5-triazine, N,N2 -carbonyldiimidazole. Specifically, mixed anhydrides suffered from nonselective reactivity with amine 4.
  • 16
    • 72449178698 scopus 로고    scopus 로고
    • note
    • While kilogram quantities typically cost ∼$2000/kg, manufacturingscale quantities typically run an order of magnitude less at $100 to $200 per kg.
  • 18
    • 72449176608 scopus 로고    scopus 로고
    • note
    • Potassium bicarbonate allowed for higher concentrations of salts than sodium bicarbonate and therefore reduced product loss to the aqueous layer. Though potassium carbonate washes were also effective, they were not chosen to avoid the possibility of epimerization during the subsequent distillation.
  • 23
    • 72449183368 scopus 로고    scopus 로고
    • note
    • LD 50: >2005 mg/kg (rat), cutaneous irritation: nonirritant (rabbit), ocular irritation: nonirritant (rabbit). See the MSDS at Seppic (Seppic, Inc., Fairfield, NJ).
  • 24
    • 72449155812 scopus 로고    scopus 로고
    • note
    • Epimerization of the nitrile stereogenic center was observed at pH >12 under warm, alcoholic conditions.
  • 25
    • 72449165153 scopus 로고    scopus 로고
    • note
    • The water solubility of the monohydrate is 19 mg/mL.
  • 29
    • 0004275160 scopus 로고
    • Advances in Chemistry Series, 116, American Chemical Society: Washington D.C.
    • Horsley, L. H. Azeotropic Data III; Advances in Chemistry Series, 116, American Chemical Society: Washington D.C., 1973; p 21.
    • (1973) Azeotropic Data III , pp. 21
    • Horsley, L.H.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.