A New Process for the Preparation of 4-Pyridine Butanol

Abstract

The invention relates to a new preparation process of tirofiban hydrochloride key intermediate 4-pyridine butanol. The key to the process is to make the reaction intermediate 4-(4-pyridyl)-3-butyn-1-ol into hydrochloride or sulfate to improve its stability, and the corresponding salt can be hydrogenated under normal temperature and pressure to obtain the corresponding Pyridine butanol hydrochloride or sulfate, the latter can prepare high-purity 4-pyridine butanol by distillation under reduced pressure after freeing triethylamine. This route does not involve expensive reagents, has low requirements for equipment, is simple to operate, and is highly feasible for industrial scale-up.

Description

technical field [0001] The invention relates to a new preparation process of tirofiban hydrochloride key intermediate 4-pyridine butanol. [0002] Background technique [0003] Tirofiban hydrochloride (N-n-butylsulfonyl-O-4-(4-piperidinyl)butyl)-L-tyrosine hydrochloride monohydrate,) as a reversible non-peptide The platelet GPIIb / IIa receptor antagonist was developed by Merck, an international pharmaceutical giant, in the 1990s, and was successfully approved by the US FDA in May 1998. At present, the platelet antagonist has been sold in Switzerland, China, Germany and the Netherlands It is widely used in other countries. The drug is suitable for patients with unstable angina or non-Q wave myocardial infarction to prevent cardiac ischemic events. Cardiac ischemic complications associated with sudden occlusion of treated coronary arteries. The structural formula of tirofiban hydrochloride is as follows: [0004] [0005] So far, chemists have developed many synthetic r...

AI Technical Summary

Problems solved by technology

Unfortunately, we found that the intermediate 4-(4-pyridyl)-3-butyn-1-ol of this route is very unstable, difficult to store, and very difficult to separate and purify (due to the instability of the compound, degradation occurs during the purification process) ; If it is directly put into the next hydrogenation reaction without purification, a large amount of by-products will be produced and the yield will be low; in addition, the use of expensive platinum oxide as a catalyst in the hydrogenation process will increase the cost of this route

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