Synthesis method of 1H-pyrrolo[2,3-b]pyridine-2-boronic acid pinacol ester

Abstract

The invention discloses a synthesis method of 1H-pyrrolo[2,3-b]pyridine-2-boronic acid pinacol ester, and belongs to the field of medicinal chemistry. The synthesis method comprises the following steps: reacting 7-azaindole serving as a raw material with di-tert-butyl dicarbonate to synthesize 1H-pyrrolo[2,3b]pyridine-1-carboxylic acid tert-butyl ester, reacting the 1H-pyrrolo[2,3b]pyridine-1-carboxylic acid tert-butyl ester with n-butyl lithium and 1,2-dibromotetrafluoroethane at low temperature to synthesize 2-bromo-1H-pyrrolo[2,3-b]pyridine, synthesizing 2-bromo-1H-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester, removing the protective group to obtain 2-bromo-1H-pyrrolo[2,3-b]pyridine, and reacting 2-bromo-1H-pyrrolo[2,3-b]pyridine with bi-pinacol borate under the catalytic action of transition metals to obtain the target product. The raw materials and reagents are cheap and easy to obtain, reaction conditions are mild, the safety is high, the cost is low, and the preparation method is easily applied to industrial batch production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a method for synthesizing 1H-pyrrolo[2,3-b]pyridine-2-boronic acid pinacol ester. Background technique [0002] 1H-pyrrolo[2,3-b]pyridine-2-boronic acid pinacol ester (also known as 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborine Pentane-2-yl)-1H-pyrrolo[2,3-b]pyridine) is a kind of pyrrolo[2,3-b]pyridine compound, which is a very important class of pharmaceutical intermediates with large For example, it can act as an intermediate of candidate drug inhibitors of the MAP kinase family (also known as P38 kinase), and the P38 kinase signaling pathway affects the regulation of cytokines such as IL-1, IL-6, IL-8 and TNFɑ The activity of inflammation can be used to treat many chronic and acute diseases, such as various inflammations and pulmonary fibrosis; it can also be used to prepare compounds that regulate receptor protein kinases, and receptor protein tyrosine kinases (RPTKs) regulate...

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Problems solved by technology

However, the reported method has the following disadvantages: the reaction route is as long as seven steps, and the initial raw material compound 1 is not cheap, from compound 5 to compound 6, the nitrogen atom is added to tert-butoxycarbonyl (Boc), and the next step is to heat tert-butoxy The carbonyl group (Boc) is lost again, and the reaction procedure is cumbersome; compound 6 to compound 7, n-butyllithium hydrogen extraction, borate on isopropanol pinacol borate, overnight at room temperature, the reaction yield is particularly low, only 16% , and the route is long, the yield is low, and it is not suitable for repetition

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