Improvement on synthesis method of tetrahydro-beta-carboline compound (II)

Abstract

The invention relates to an improvement on a synthesis method of a tetrahydro-beta-carboline compound (II). The method comprises reacting D-tryptophan methyl ester hydrochloride and piperonal at 50 DEG C-150 DEG C in a certain solvent to obtain hydrochloride of a structural formula (II) compound, wherein the solvent can be nitroethane, dioxane, methylbenzene, dimethylbenzene, benzene or nitrobenzene. The yield and purity of products prepared by the method are greatly improved, and the method is especially suitable for industrial production.

Description

field of invention The invention relates to an improvement of a synthesis method of a tetrahydro-β-carboline compound. Background of the invention U.S. Patent No. 5,859,006 discloses that tadalafil has the structure (I) (6R, 12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-sub-bis) Methoxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione compound, which is cyclic guanosine monophosphate ( A selective, reversible inhibitor of cGMP)-specific phosphodiesterase 5 (PDE5) for the treatment of erectile dysfunction in men. Compound (I) has two asymmetric carbon atoms, each represented by an asterisk, wherein the non-hydrogen substituents on the asymmetric carbon atoms are in the cis configuration. Compound (I) can be prepared by two synthetic routes disclosed in US Patent No. 5,859,006. Route A Route B The route from compound (II) to compound (I) The overall yield of compound (I) prepared by synthetic route (A) or (B) is about 25%. Synthetic route (B) requires...

AI Technical Summary

Problems solved by technology

Improvement route (A) in the field is especially an advance, it utilizes the Pickett-Spengler between D-tryptophan methyl ester and 3,4-methylenedioxybenzaldehyde or other aromatic aldehydes reaction, prepare enantiopure compound (II) or similar tetrahydro-β-carboline compound with simple and direct method, it also overcomes the shortcoming of typical Pickett-Spengler reaction, such as using TFA, reaction time Long and difficult to separate the product

However, the current Pickett-Spengler reaction still has the disadvantages of low yield and low purity.

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