IDO1抑制剂INCB024360的合成工艺
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O626;O625.6

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Optimization of the Synthetic Process of INCB024360 as IDO1 Inhibitor
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    摘要:

    以丙二腈为原料,通过一锅法,经过四个连续反应,得到3-氨基-4-氨基肟基呋咱,经Sandmeyer反应生成3-氨基-4-酰氯肟基呋咱,再与3-氯-4氟苯胺反应得到吲哚胺2,3-双加氧酶抑制剂4-氨基-N-(3-氯-4-氟苯基)-N'-羟基-1,2,5-恶二唑-3-甲脒(INCB024360)。最优合成工艺条件下,总产率从10.0%提高到43.1%,HPLC纯度为99.6%,其结构经1H NMR,13C NMR,MS表征。

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    3-amino-4-amino oximidofurazan was obtained from the malononitrile through the one pot method of four-step consecutive reaction, which was diazotized by the Sandmeyer raction to get 3-amino-4-acid chloride oximidofurazan. Then, it was converted into 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide(INCB024360) via the substitution with 3-chloro-4-fluoro aniline with the overall yield increased from 10.0% to 43.1% and the HPLC purity of 99.6% in the best synthetic process. The structures were characterized by 1H NMR, 13C NMR, MS.

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胡昆,樊志强,任杰. IDO1抑制剂INCB024360的合成工艺[J].精细化工,2015,32(9):

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  • 收稿日期:2015-03-09
  • 最后修改日期:2015-05-12
  • 录用日期:2015-05-25
  • 在线发布日期: 2015-08-12
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