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The invention provides a label-free magnetic self-assembly nanoprobe, a construction method thereof and application of the label-free magnetic self-assembly nanoprobe in detection of PrPC protein. The label-free magnetic self-assembly nanoprobe disclosed by the invention comprises a magnetic Fe3O4 / Fe2O3 (at) Au heteroplasmon nanorod array and a sulfhydrylation aptamer nucleic acid chain which is combined with the magnetic Fe3O4 / Fe2O3 (at) Au heteroplasmon nanorod array through an Au-S bond; a biosensor prepared from the label-free magnetic self-assembly nanoprobe is good in reproducibility and stability; the RSD value of multiple times of detection (intraday / day) is 1.55%; the storage time of multiple groups of sensors is 0-15 days, and the change of response signal values does not exceed 4%; the biosensor has a relatively low detection limit (1pg / mL), a relatively wide linear range (1 * 10 < pg / mL >-1 * 10 < 5 > pg / mL) and relatively good sensitivity, has very good application in detection of PrPC, and has very good practicability.

This invention discloses a method for synthesizing an intermediate of retinoic acid, relating to the field of pharmaceutical organic synthesis technology, comprising the following steps: S1, in the presence of a base, 2-amino-3-chloropyridine and 4-bromopiperidine undergo a nucleophilic substitution reaction in solvent A to prepare compound III; S2, in the presence of a catalyst and ammonia solution, compound III undergoes an amination reaction in solvent B to prepare compound II; S3, compound II is dissolved in solvent C, and sequentially undergoes CDI cyclization and hydrogen chloride solution salt formation to prepare compound I, namely 1-(piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one. This invention is low-cost, uses mild reaction conditions, has a simple synthesis process, high yield, and eliminates the need for expensive and potentially unsafe excipients, effectively improving reaction safety, being environmentally friendly, and suitable for industrial production.