Practical syntheses of a CXCR3 antagonist.
Practical syntheses of a CXCR3 antagonist.
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CXCR3拮抗剂的实际合成。
DOI：
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发表时间：
2011
影响因子：
3.6
通讯作者：
J. Murry
中科院分区：
文献类型：
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作者：
Johann Chan;B. Burke;Kyle D. Baucom;K. Hansen;M. Bio;E. Divirgilio;M. Faul;J. Murry
描述了两种新的、可靠的CXCR 3受体的吡啶并[2，3-d]-嘧啶抑制剂的合成。以数千克规模证明了从2-氨基烟酸合成CXCR 3抑制剂（1）的九步合成，并采用经典的拆分方法来提供对映体富集的活性药物成分（API）。CXCR 3抑制剂的第二种合成从（+）-（D）-Boc丙氨酸和2-氯烟酸开始，并利用Goldberg偶联。以克级进行的第二次合成与前一路线相交于共同的中间体，从而以更高的总产率完成对映体富集的API的正式合成，而不需要拆分。
Two new, reliable syntheses of a pyrido[2,3-d]-pyrimidine inhibitor of the CXCR3 receptor are described. A nine-step synthesis of the CXCR3 inhibitor (1) from 2-aminonicotinic acid was demonstrated on a multikilogram scale and incorporates a classic resolution to deliver the enantioenriched active pharmaceutical ingredient (API). A second synthesis of the CXCR3 inhibitor starts from (+)-(D)-Boc alanine and 2-chloronicotinic acid and utilizes a Goldberg coupling. This second synthesis, performed on a gram scale, intersects the former route at a common intermediate thereby completing a formal synthesis of the enantioenriched API in higher overall yield without the need for a resolution.