2-Benzyl-3-morpholino-7-(thiophen-2-yl)-6-(thiophen-2-ylmethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

Round 1

Reviewer 1 Report

The authors present a Short Note article, the content fits the article type selected.

The title is the systematic name of the original compound described in the article. Please capitalize the first letter (ie Benzyl).

The preparation of the title compound is performed using a elegant synthetic route.

Language, figures and schemes are of good quality.

 

Minor corrections:

Line 39, please delete “The” before canaglifozin.

Line 118, please delete “General procedure”.

For the preparation of compound 1, please provides the amount of reagents in grams or mL as well as the mass od obtained compound 1.

Author Response

Replies to Referee 1

Referee 1: Comments to the Author: The authors present a Short Note article, the content fits the article type selected. The title is the systematic name of the original compound described in the article. Please capitalize the first letter (ie Benzyl). The preparation of the title compound is performed using a elegant synthetic route. Language, figures and schemes are of good quality

Authors: We thank our Referee 1 for the time spent in the reviewing process and for his/her helpful comments. The tittle has been modified accordingly.

Referee 1: Minor corrections: Line 39, please delete “The” before canaglifozin. Line 118, please delete “General procedure”. For the preparation of compound 1, please provides the amount of reagents in grams or mL as well as the mass od obtained compound 1.

Authors: Thank you very much for your recommendation. In the revised version of the manuscript, all these observations were attended.

Reviewer 2 Report

This manuscript describes a one-pot synthesis of multi-substituted pyridinone derivative 1 via Ugi-Zhu reaction, aza-Diel-Alder reaction, N-acylation, and aromatization.  The synthesis described in this paper is of elegant and efficient for the preparation of the compound 1 in good yield. 

However, the manuscript described only the synthesis of 1.  If the target molecule was a natural or some other biologically active compound, the current work might be recognized as an elegant total synthesis of natural or unnatural compound.  But it is not the case.  Although the current work is demonstrating an efficient synthetic methodology, unfortunately, I cannot judge the generality, applicability, scope and limitation from the limited example shown in this paper.  I would like to suggest that describe few more examples of the one-pot synthesis using a variety of segments apart from compounds 2, 3, and 6.  Furthermore, the optimization process tried to fine the best conditions as mentioned by the authors in the text (page 2, line 64-67) can be included in the manuscript.  It is also be of useful information for the readers.  This paper could be a full paper including more information mentioned above.

 

At this stage, I conclude that the chemistry described in this manuscript does not reach to the scientific level required, and do not recommend for publication in Molbank.

Author Response

Replies to Referee 2

Referee 2: This manuscript describes a one-pot synthesis of multi-substituted pyridinone derivative 1 via Ugi-Zhu reaction, aza-Diel-Alder reaction, N-acylation, and aromatization. The synthesis described in this paper is of elegant and efficient for the preparation of the compound 1 in good yield. However, the manuscript described only the synthesis of 1. If the target molecule was a natural or some other biologically active compound, the current work might be recognized as an elegant total synthesis of natural or unnatural compound. But it is not the case. Although the current work is demonstrating an efficient synthetic methodology, unfortunately, I cannot judge the generality, applicability, scope and limitation from the limited example shown in this paper. I would like to suggest that describe few more examples of the one-pot synthesis using a variety of segments apart from compounds 2, 3, and 6. Furthermore, the optimization process tried to fine the best conditions as mentioned by the authors in the text (page 2, line 64-67) can be included in the manuscript. It is also be of useful information for the readers. This paper could be a full paper including more information mentioned above. At this stage, I conclude that the chemistry described in this manuscript does not reach to the scientific level required, and do not recommend for publication in Molbank.

Authors: We thank Referee 2 for the time spent in the reviewing process and for his/her comments. However, respectfully we regret the opinion of Reviewer #2 about our short note because the Molbank journal accepts manuscripts describing the synthesis and structural characterization of single compounds, of course as long as they are new, namely compounds that have not been synthesized nor isolated, anywhere. Indeed, at the beginning of MB website (https://www.mdpi.com/journal/molbank), it can be found the next paragraph ‘Molbank is a peer-reviewed, open access journal comprised of a unique collection of one-compound-per-paper short notes on synthetic compounds and natural products’. Thus, our aim was to describe for the first time the synthesis of a new and complex tetraheterocycle containing a couple of thiophene rings bound to a pyrrolo[3,4-b]pyridin-5-one core, which only can be performed by using an Ugi-Zhu three-component reaction coupled to a one pot cascade process aza Diels-Alder / N-acylation / decarboxylation / dehydration. However, We absolutely agree with the last point from our Reviewer #2, which was attended. As it can be seen in the revised version of the manuscript, it now includes a new table 1 to show the screening behind optimal reaction conditions. The new table 1 contains a scheme about the general methodology, which has been separated from the reaction mechanism to make the paper more understandable.

Round 2

Reviewer 2 Report

I understand the author’s statement and agree with that.  Furthermore, the revised manuscript includes the result of the optimization.

Chemistries described in this paper would be a nice piece of work and of interest for a number of researchers in this field.

I recommend this manuscript for publication in Molbank.

 

Author Response

Replies to Referee 2

Referee 2: I understand the author’s statement and agree with that.  Furthermore, the revised manuscript includes the result of the optimization.

Chemistries described in this paper would be a nice piece of work and of interest for a number of researchers in this field.

I recommend this manuscript for publication in Molbank.

Authors: We thank our Referee 2 for the time spent in the reviewing process and for his/her helpful comments.