793669-26-8Relevant articles and documents
Preparation method and application of Smo inhibitor based on Nebivolol
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Paragraph 0042; 0044; 0057-0062, (2019/10/17)
The invention discloses a preparation method and an application of a Smo inhibitor based on Nebivolol. The structural formula of the Smo inhibitor is as shown in a formula (I). The invention further discloses a synthetic method and an application of the Smo inhibitor. According to the Smo inhibitor, a beta-receptor retardant Nebivolol with inhibitory activity for Smo proteins serves as a lead compound, and optimization reconstruction is implemented based on the beta-receptor retardant Nebivolol to obtain the Smo inhibitor with good inhibitory activity.
Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates
Devi, Runjun,Das, Sajal Kumar
supporting information, p. 571 - 578 (2017/03/29)
While the exploitation of the Sharpless asymmetric dihydroxylation as the source of chirality in the synthesis of acyclic molecules and saturated heterocycles has been tremendous, its synthetic utility toward chiral benzo-annulated heterocycles is relatively limited. Thus, in the search for wider applications of Sharpless asymmetric dihydroxylation-derived diols for the synthesis of benzo-annulated heterocycles, we report herein our studies in the asymmetric synthesis of (R)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol, (R)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol and (S)-6-fluoro-2-((R)-oxiran-2-yl)chroman, which have been used as late-stage intermediates for the asymmetric synthesis of the antihypertensive drug (S,R,R,R)-nebivolol. Noteworthy is that a large number of racemic and asymmetric syntheses of nebivolol and their intermediates have been described in the literature, however, the Sharpless asymmetric dihydroxylation has never been employed as the sole source of chirality for this purpose.
Preparation of 6-fluoro -3,4-dihydro -2H-1-benzopyran-2-oxirane improved method
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Paragraph 0068; 0069; 0070, (2016/10/07)
The invention relates to an improvement method for preparing a nebivolol key intermediate, namely 6-fluorin-3,4-dihydro-2H-1-benzopyranyl-2-epoxy ethane. The method comprises the following steps of: (a) condensing a compound (IV) and dihalogenated methane in the presence of an organic metal lithium compound to obtain a compound (II); (b) reducing the compound (II) to obtain a compound (III); and (c) performing cyclization on the compound (III) under alkaline condition to obtain a compound (I). The scheme of the invention has the advantages of readily available raw materials, easiness in operating, greatly increased reaction yield and purity and high contribution to industrial mass production.
