公开(公告)号：WO2015013715A3

公开(公告)日：2015-10-29

申请号：PCT/US2014048472

申请日：2014-07-28

Applicant: THR REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： HARTWIG JOHN ,  FIER PATRICK

IPC: C07D213/61

CPC classification number: C07D213/61 ,  C07D213/63 ,  C07D213/65 ,  C07D213/75 ,  C07D213/79 ,  C07D213/80 ,  C07D213/803 ,  C07D213/81 ,  C07D213/82 ,  C07D215/18 ,  C07D239/42 ,  C07D239/46 ,  C07D401/04 ,  C07D405/04

Abstract: The present invention provides compositions and methods for the selective C-H fluorination of nitrogen-containing heteroarenes with AgF2, which has previously been considered too reactive for practical, selective C-H fluorination. Fluorinated heteroarenes are prevalent in numerous pharmaceuticals, agrochemicals and materials. However, the reactions used to introduce fluorine into these molecules require pre-functionalized substrates or the use of F2 gas. The present invention provides a mild and general method for the C-H fluorination of nitrogen-containing heteroarene compounds to 2-fluoro-heteroarenes with commercially available AgF2. In various embodiments, these reactions occur at ambient temperature within one hour and occur with exclusive selectivity for fluorination at the 2-position. Exemplary reaction conditions are effective for fluorinating diazine heteroarenes to form a single fluorinated isomer.

Abstract translation: 本发明提供了含有AgF 2的含氮杂芳烃选择性C-H氟化的组合物和方法，其先前被认为对于实际的选择性C-H氟化反应过大。 氟化杂芳烃在许多药物，农药和材料中是普遍存在的。 然而，用于将氟引入这些分子的反应需要预功能化的底物或使用F2气体。 本发明提供了一种使用市售的AgF2将含氮杂芳烃化合物C-H氟化为2-氟 - 杂芳烃的温和的一般方法。 在各种实施方案中，这些反应在环境温度下在1小时内发生，并且以2-位氟化的排他选择性发生。 示例性的反应条件对于使二嗪杂芳族化合物氟化以形成单一氟化异构体是有效的。