کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5217831 | 1383308 | 2013 | 8 صفحه PDF | دانلود رایگان |
A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6-chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100-110 °C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core.
Journal: Tetrahedron - Volume 69, Issue 40, 7 October 2013, Pages 8564-8571