Ethyl 6-Methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Round 1

Reviewer 1 Report

The authors present a convenient method for the synthesis of Ethyl 6-methy-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate via a multicomponent Biginelli reaction.

It should be interesting that the authors explain in the introduction why they prepared this compound. Is it for a biological evaluation purpose?

I would recommend publication of this work in Molbank after minor revisions.

I have the following recommendations:

            -  a ref describing a one pot-procedure to similar compounds should be added: Peyman, S. et al. Mol Divers (2011) 15:833-837.

-          Page 2, line 61: term “benzylic hydrogen” is not appropriate. The CH is part of the pyrimidinone moiety and the phenyl ring is a substituent of the pyrimidinone. It can be “pyrimidyl CH” or “H-4”.

-          Page 2, line 64: idem, term “allylic CH3” is not appropriate. The CH3 is a substituent of the pyrimidinone. It should be “6-methyl”.

-          Page 2, line 65: proton NMR description: “multiplet” should be replaced with “quartet”.

-          Materials and methods:

o   NMR data should be given with two decimal places for protons and one decimal place for carbon;

o   Line 82, please give the corresponding mass to 1.1 mmol of sodium azide;

o   Description of compound 5: signal at 4.08 ppm should be a quartet?

o   Description of compound 6: please check the first sentence, there is no verb. (one proposal: “were charged”); line  “terc-butanol” should be “tert-butanol).

-          Bibliographical data:

Ref 4: page numbers “971-974” instead of “971-4”. Idem for references 7, 9 and 11.

Author Response

Please find attached manuscript entitled “Ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate” authored by I. L. Gonçalves et. al to be considered for publication in Molbank. We would like to thank for their comments. Our paper has been completely revised, and we have made alterations in the paper, as suggested. The modifications performed were send with our comments.

Kindest regards

The authors

The authors present a convenient method for the synthesis of Ethyl 6-methy-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate via a multicomponent Biginelli reaction.

It should be interesting that the authors explain in the introduction why they prepared this compound. Is it for a biological evaluation purpose?

We agree with the referee. Information about aim of the compound title preparation was added.

I would recommend publication of this work in Molbank after minor revisions. I have the following recommendations:

-  a ref describing a one pot-procedure to similar compounds should be added: Peyman, S. et al. Mol Divers (2011) 15:833-837.

This reference was previously cited. Please see the reference number 11.

Page 2, line 61: term “benzylic hydrogen” is not appropriate. The CH is part of the pyrimidinone moiety and the phenyl ring is a substituent of the pyrimidinone. It can be “pyrimidyl CH” or “H-4”.

We agree with the referee. The correction was performed.

Page 2, line 64: idem, term “allylic CH3” is not appropriate. The CH3 is a substituent of the pyrimidinone. It should be “6-methyl”.

We agree with the referee. The corrections were performed.

Page 2, line 65: proton NMR description: “multiplet” should be replaced with “quartet”.

We agree with the referee. The correction was performed.

Materials and methods:

- NMR data should be given with two decimal places for protons and one decimal place for carbon;

We agree with the referee. The modification was performed.

-  Line 82, please give the corresponding mass to 1.1 mmol of sodium azide;

We agree with the referee. The modification was performed.

- Description of compound 5: signal at 4.08 ppm should be a quartet?

This signal is better characterized as multiplet, due to the detection of vicinal coupling between methylene hydrogens. The expansion of this signal may be found in Figure S1 of supporting information.

- Description of compound 6: please check the first sentence, there is no verb. (one proposal: “were charged”); line “terc-butanol” should be “tert-butanol).

We agree with the referee. The modification was performed.

- Bibliographical data:

Ref 4: page numbers “971-974” instead of “971-4”. Idem for references 7, 9 and 11.

We agree with the referee. The modifications were performed.

Reviewer 2 Report

Editor should check English and  editorial format before send MS out for peer review.

The MS is full of English and editorial issues. Some examples are list below:

P1, L23, reaction having as key step; four step route

P1, L28, Italian chemist

P1, L34, is widely investigated, should be “has been…”

P2, L50, acetone, reflux and potassium carbonate…?

P2, L51, The Biginelli reaction catalyzed by

P2, 54, used as a starting material

P2, L55, 84 %

P2, L55, Very similar compounds to the reported here…?

Author Response

Please find attached manuscript entitled “Ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate” authored by I. L. Gonçalves et. al to be considered for publication in Molbank. We would like to thank for their comments. Our paper has been completely revised, and we have made alterations in the paper, as suggested. 

Kindest regards

Reviewer 3 Report

The compound has not been previously reported and as such fits into the Molbank journal. However, the authors also describe several compounds which are literature. I see no reason why the experimental section should contain this information unless there has been a significant change in experimental protocol. As such, the authors should only report in the Expt Sect the synthesis of the final step from (i.e. 5+7 = 8). They can of course show Scheme 1 describing how compds 2, 5 and 7 are prepared, but there is no reason to include their preparation in the Expt Sect. A citation for the preparation of each lit compd should suffice.

Compd 8 however, should be fully characterised. The following needs to be included:

1) FTIR

2) UV-vis

3) Microwave irradiation was used, but the authors do not mention the type of instrument nor indicate the pressure within the sealed reaction tube. How did they measure the internal rxn temperature. This missing information must be included.

4) Can the authors at least assign whether the 13C peaks are C (s), CH (d), CH2 (t), CH3 (q)?

some minor points:

1H in the compd nomenclature should have the H in italics

In the Abstract the authors should give the yield of the product either for the last step (5 to 8) or the overall yield and number of steps etc

carboxylateidentified ? needs a space

13C NMR data to 1 dp
J italic
yield should be accompanied by mass isolated
there is no need to repeat 'recrystallized from ethanol' simply give the following data: m.p. 184-186 ^oC (EtOH)
m/z should be italic

remove issue numbers from references, simply report the year, vol, page range

Author Response

Please find attached manuscript entitled “Ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate” authored by I. L. Gonçalves et. al to be considered for publication in Molbank. We would like to thank for their comments. Our paper has been completely revised, and we have made alterations in the paper, as suggested. The modifications performed were send with our comments.

Kindest regards

The authors

 The compound has not been previously reported and as such fits into the Molbank journal. However, the authors also describe several compounds which are literature. I see no reason why the experimental section should contain this information unless there has been a significant change in experimental protocol. As such, the authors should only report in the Expt Sect the synthesis of the final step from (i.e. 5+7 = 8). They can of course show Scheme 1 describing how compds 2, 5 and 7 are prepared, but there is no reason to include their preparation in the Expt Sect. A citation for the preparation of each lit compd should suffice.

Some steps contain small modifications, which makes necessary its full description in methodology.

Compound 8 however, should be fully characterized. The following needs to be included:

1) FTIR

The FT-IR spectrum of compound 8 was added to the supporting information and in the description of spectral data compound.

2) UV-vis

The UV-vis spectrum of compound 8 was added to the supporting information and in the description of spectral data compound.

3) Microwave irradiation was used, but the authors do not mention the type of instrument nor indicate the pressure within the sealed reaction tube. How did they measure the internal rxn temperature. This missing information must be included.

We agree with the referee. This information was added to the methodology.

4) Can the authors at least assign whether the 13C peaks are C (s), CH (d), CH2 (t), CH3 (q)?

We agree with the referee. This information was added.

some minor points: 1H in the compd nomenclature should have the H in italics

We agree with the referee. The modifications were performed.

In the Abstract the authors should give the yield of the product either for the last step (5 to 8) or the overall yield and number of steps etc

We agree with the referee. This information was added to the abstract.

carboxylateidentified ? needs a space

We agree with the referee. The correction was performed.

 13C NMR data to 1 dp

We agree with the referee. The modification was performed.

 J italic

We agree with the referee. The modification was performed.

 yield should be accompanied by mass isolated

We agree with the referee. This information was added.

 there is no need to repeat 'recrystallized from ethanol' simply give the following data: m.p. 184-186oC (EtOH)

We agree with the referee. The modification was performed.

 m/z should be italic

We agree with the referee. The modification was performed.

 remove issue numbers from references, simply report the year, vol, page range

We agree with the referee. The modification was performed.