Preparation method of Ramelteon

Abstract

The invention relates to a preparation method of Ramelteon. The method mainly comprises three reaction steps of hydrogenation, chiral resolution and acylation reaction. According to the synthesis of the Ramelteon, 2-(1,6,7,8-tetralin-2H-indeno[5,4-b]furan-8-subunit) ethylamine hydrochloride serves as a start raw material, Pd-C serves as a catalyst, and 2-(1,6,7,8-tetralin-2H-indeno[5,4-b]furan-8-base) ethylamine hydrochloride, namely an midbody-1, is acquired through catalytic hydrogenation; chiral resolution is conducted on the midbody-1 through dibenzoyl-L-tartrate, so that (S)-2-(1,6,7,8-tetralin-2H-indeno[5,4-b]furan-8-base) ethylamine dibenzoyl-L-tartrate, namely a midbody-2, is acquired; an acylation reaction is conducted on the midbody-2 and propionyl chloride, so that a crude product of the Ramelteon is acquired, and a finished product of the Ramelteon is acquired after the crude product is refined and qualified.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of ramelteon. Background technique [0002] Ramelteon, chemical name: (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl] Propionamide, the structural formula is: [0003] [0004] Ramelteon is a potent and highly selective melatonin receptor agonist. It is currently the only melatonin receptor agonist on the market for the treatment of insomnia with difficulty falling asleep. It is also effective for chronic insomnia and short-term insomnia. Efficacy: Because this product has no dependence and drug abuse tendency, FDA lists it as an unregulated hypnotic drug. With the rapid development of society, the acceleration of the pace of life, the increase of work pressure, people's spirits are in a state of tension, resulting in more and more patients with insomnia, and the incidence rate continues to rise. Therefore, the drug market fo...

AI Technical Summary

Problems solved by technology

Wherein the chiral catalytic reagent used in route one asymmetric hydrogenation is more expensive, and the requirements for hydrogenation operation are relatively harsh, and the process stability is poor; adopt the method of route secondary resolution, the chiral resolution reagent used is cheap, and The operation is relatively simple, and it is more suitable for industrial scale-up production; the route 3 using chiral column chromatography is only suitable for laboratory-scale sample preparation, which has high requirements for operators and is difficult for industrialization

The chiral resolution of Route 2 has many advantages, but it still needs other steps to improve the quality of the finished product, increase the purity and yield

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