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 S_NAr 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 S_NAr 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.

会聚和选择性血管内皮生长因子受体（VEGFR）的简化合成2个激酶抑制剂已经被采用根据上一个S的合成策略来实现_Ñ 6-氯咪唑并[1,2的氩反应b与酚在最终步骤]哒嗪。对于6-氯咪唑并[1,2的合成b ]哒嗪，使用一锅反应的3-氨基-6-氯哒嗪，环丙烷甲酰胺，和溴乙酰溴被开发。酚很容易通过3-氨基酚与吡唑羧酸酰化化学选择性制备，并且的有效和高产合成Ñ也被开发-ethylpyrazole。在S _Ñ 6-氯咪唑的氩反应[1,2 b在碳酸铯的存在下，]哒嗪与苯酚在DMSO中成功地在100–110°C下进行，以高收率得到目标产物。这种新的自由色谱-过程将是不仅对这些化合物的进一步批量供应到包含6醚化的咪唑并[1,2其它化合物的合成有用的，但也可以适用b ]哒嗪-2-胺核心。