5 results about "Sitafloxacin" patented technology

This invention provides a compound, its preparation method, and its application, as well as a method for preparing a five-membered ring intermediate of sitafloxacin, relating to the field of chemical drug preparation technology. The compound provided by this invention has the structure shown in Formula 1. In this invention, the compound shown in Formula 1 is a novel intermediate. Using it to prepare the five-membered ring intermediate of sitafloxacin (Formula 3) requires no Pd / C and hydrogenation process, and does not form a five-membered ring-opening impurity (Formula 6). The process is simple and suitable for industrial production. This invention provides a method for preparing the five-membered ring intermediate of sitafloxacin (structure shown in Formula 3). In the embodiments of this invention, the prepared five-membered ring intermediate of sitafloxacin with the structure shown in Formula 3 was analyzed by HPLC, and no ring-opening impurity as shown in Formula 6 was detected, with a high yield. Formula 1.

The application relates to the field of drug synthesis, and particularly discloses a high-efficiency asymmetric synthesis method of a sitafloxacin intermediate (1S, 2S)-2-fluorocyclopropane carboxylic acid, which comprises the following steps: S1. reacting a compound SM1 with a chiral compound SM2 in a solvent under the action of an alkali to obtain an epoxide ring-opening chiral compound 1; S2. introducing a group into a hydroxyl group in the compound 1 to obtain a compound 2; S3. obtaining an absolute chiral configuration cyclopropane compound 3 from the compound 2 under the action of an alkali; S4. obtaining an absolute chiral configuration compound 4 from the compound 3 after a deprotection group; S5. generating an absolute chiral configuration compound 5 by oxidizing the compound 4 with an oxidizing agent; and S5. removing a benzene (sulfo) sulfonyl group from the compound 5 to obtain the absolute chiral configuration (1S, 2S)-2-fluorocyclopropane carboxylic acid. The preparation method has the advantages that starting materials are easy to obtain, each step in the synthesis process is simple in operation and separation and extraction, the reaction conditions are mild, the cis-trans selectivity is special, the enantioselectivity is high, the total yield and production capacity are high, and the method is suitable for large-scale industrial production.

This invention relates to a method for synthesizing the sitafloxacin intermediate 5-benzyl-7(S)-tert-butoxycarbonylamino-5-azaspiro[2,4]heptane. The method uses 1-benzylmethylpyrrolidine-2,4-dione as the starting material and proceeds through five steps: cyclization, oxime formation, chiral asymmetric reduction, salt formation, and amino protection to obtain the target product. Specifically, the cyclization reaction uses an alkylating agent and a base to construct a spirocyclic structure; the oxime reaction introduces a methoxyimino group via methoxyamine hydrochloride; the chiral asymmetric reduction uses a catalytic system composed of a chiral ligand and a boron reagent to construct the chiral center, followed by purification via maleic acid salt formation; and finally, the amino group is protected with di-tert-butyl dicarbonate to obtain the target product. This invention offers high atom economy, good process scalability, simple operation, controllable cost, and high product purity, providing a reliable intermediate synthesis scheme for the efficient preparation of sitafloxacin active pharmaceutical ingredient.

The application provides a sitafloxacin intermediate and an enzymatic preparation method and application thereof, and belongs to the technical field of organic synthesis and enzyme catalysis. The sitafloxacin intermediate compound 3 is a key chiral intermediate for preparing sitafloxacin. The preparation method comprises the following steps: (1) reacting compound 1 with an azide reagent to obtain compound 2; (2) catalyzing and reacting compound 2 by using a transaminase to obtain compound 3. The preparation method for preparing compound TM by using compound 3 comprises the following steps: (A) reducing compound 3 by using a reducing reagent and carrying out amine-ester exchange to obtain compound 4; (B) reacting compound 4 with a Boc reagent to obtain compound 5; (C) reducing compound 5 to obtain product TM. The process is simple in operation, conventional reaction equipment is used, raw materials are cheap and easy to obtain, the yield is high, the process introduces the biological enzyme catalysis technology, high stereoselectivity product is obtained, and the cost is greatly reduced.

The invention belongs to the field of chemical drug synthesis, and particularly relates to a preparation method of an antibacterial drug sitafloxacin intermediate. The preparation method comprises the following steps: carrying out condensation reaction on a compound I and N, N-dimethylformamide dimethyl acetal to prepare an intermediate IV; the intermediate IV and (1R, 2S)-1-amino-2-fluorocyclopropane are subjected to a substitution reaction, and an antibacterial drug sitafloxacin intermediate compound III is prepared. The preparation method disclosed by the invention has the advantages of mild reaction conditions, short reaction time, small and single solvent dosage, high reaction conversion rate and high selectivity, and meets the requirements of industrial large-scale production.