877674-77-6

Usage

Uses

Used in Pharmaceutical Industry:
7-Chloro-2-[[[(1S)-2,2-dimethylcyclopropyl]carbonyl]amino]-2-heptenoic acid is used as a reagent for the preparation of Cilastatin (C441105), an antibiotic adjunct. It plays a crucial role in preventing the renal metabolism of penem and carbapenem antibiotics by specifically and reversibly inhibiting dehydropeptidase I, thereby enhancing the effectiveness of these antibiotics and reducing their potential side effects.

Upstream product

• 877758-94-6 (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester 
• 1022895-92-6 ethyl 7-chloro-2-{[(1S)-2,2-dimethylcyclopropyl]formamido}hept-2-enoate 
• 78834-75-0 ethyl-7-Chloro-2-oxoheptanoate 
• 75885-58-4 (S)-2,2-dimethylcyclopropanecarboxamide 
• 166037-21-4 (E)-7-chloro-2[[(1S)-2,2-dimethyl cyclopropane]carboxamide]-2-heptenoic acid 

Downstream Products

• 82009-34-5 cilastatine 

Relevant academic research and scientific papers

Cilastatin sodium intermediate preparation method

The invention belongs to the technical field of medicines, and particularly provides a cilastatin sodium intermediate preparation method, which comprises: simply preparing a (Z)-7-X-2((2s)-2,2-dimethylcyclopropaneformamido)-2-heptenoic acid crude product through a one-pot method by using 7-X-2-oxoheptanoic acid ethyl ester and (s)-2,2-dimethylcyclopropaneformamide as raw materials sequentially under the action of a catalyst, concentrated hydrochloric acid and hydrogen chloride gas, and re-crystallizing to prepare a (Z)-7-X-2((2s)-2,2-dimethylcyclopropaneformamido)-2-heptenoic acid refined product. According to the invention, the method has advantages of short synthetic route, simple operation and high product purity, and is suitableness for industrial production.

Refining method of cilastatin

The invention provides a refining method of cilastatin. The method comprises the steps of carrying out impurity removal and concentration on a solution containing [R-[R*,S*(Z)]]-7-[(2-amino-2-carboxyethyl)-thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]-2-heptenoic acid. The method is high in production efficiency, a few in impurities, simple and convenient to operate and suitable for industrialized production and further, the obtained [R-[R*,S*(Z)]]-7-[(2-amino-2-carboxyethyl)-thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]-2-heptenoic acid has the purity which can be up to 99.9 percent and the yield which can reach 96 percent or above.

Purification method of ethyl 7-chloro-2-oxoheptanoate

The invention provides a purification method of ethyl 7-chloro-2-oxoheptanoate, wherein the purification method comprises the steps: firstly, carrying out a reaction of ethyl 7-chloro-2-oxoheptanoate oil crude product and a hydrosulphite solution, and separating to obtain a sulfite solid of ethyl 7-chloro-2-oxoheptanoate; then, dissolving the sulfite solid of ethyl 7-chloro-2-oxoheptanoate in water, adding an acid or alkali at a certain temperature, and decomposing the sulfite of ethyl 7-chloro-2-oxoheptanoate into ethyl 7-chloro-2-oxoheptanoate; and finally, extracting with an organic solvent immiscible with water, to obtain ethyl 7-chloro-2-oxoheptanoate having the purity improved. The method is simple in operation and suitable for industrialized production, and ensures the purity of a subsequent product and final product cilastatin sodium.

An improved process for the preparation of cilastatin acid

The present invention relates to an improved process for the preparation of Cilastatin Sodium of formula (I). The present invention also provides an isolation technique for Cilastatin acid from the reaction mixture.

Process for the Preparation of Cilastatin and Sodium Salt

The present invention relates to an improved process for the preparation of Cilastatin Sodium of formula (I). The present invention also provides an isolation technique for Cilastatin acid from the reaction mixture.

Preparation method for (Z)-7-chloro-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid

Provided is a novel preparation method of (Z)-7-chloro-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid represented by the following formula (1), a key intermediate of cilastatin used as a supplement to imipenem. The novel preparation method of the invention produces a pure (Z)-7-chloro-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid, a key intermediate of cilastatin, by selective hydrolysis of E isomers.

NOVEL PROCESS FOR THE PREPARATION OF CILASTATIN SODIUM SALT

The present invention relates to a novel process for preparing cilastatin sodium salt used asa dehydropeptidase 1 inhibitor. The novel method of the present invention could prevent the formation of (E)-isomer from the preparation of intermediate for preparing cilastatin sodium, i.e., (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxarnido)-2-heptenoic acid metal salt and isolate the intermediate in situ providing simpler process with high yield and purity. Furthermore, it can provide with highly pure cilastatin sodium salt by isolating novel cilastatin amine salt and using by sodium hydroxide and cationic exchange resin. Accordingly, the method can be very useful in preparing cilastatin sodium salt with high yield and high purity.