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4th April 2013 @ 00:08
Mnr: MNR111-120

Attempted bromination of MNR89 at the 7 position rather than the 6 position. 

As for WO2011093684  (A2) ― 2011-08-04 - page 19 step 2

Starting material - Synthesis of thienopyrimidine MNR89-2

 

Hazard Assessment

 

 

 

Procedure

MNR89-2 (0.30 g, 1.97 mmol) was dissolved in acetic acid (2 ml) (*2 mL was used to make up volume in the reaction tube).  Bromine (0.3 mL, 5.91 mmol) was added and the reaction was stirred in a sealed tube at 120 °C for 14 hours.  The reaction mixture was cooled to room temperature and a precipitate had formed in the brown reaction mixture.  The reaction mixture was transfered to a round bottomed flask ans rinsed with EtOAc (10 mL).  The mixture was distilled to remove the EtOAc then under reduced pressure to remove the acetic acid. 

** During the distillation, the reaction mixture bumped across the apparatus.  It was decided at this stage to rinse and filter everything.  The glassware was washed with EtOAc and water to give a pale brown solid which was dried under vacuum (0.205 g, 1.35 mmol, 68%) 

NMR

 

mnr118-1_filter_1H.pdf
mnr118-1_filter.zip

 

1H NMR consistent with literature

 

Conclusion

Title product produced in reasonable yield, taken on to the next step to prove substituion at the correct position.

Strings

Starting material

InChI=1S/C6H4N2OS/c9-6-5-4(1-2-10-5)7-3-8-6/h1-3H,(H,7,8,9) 

Product

InChI=1S/C6H3BrN2OS/c7-3-1-11-5-4(3)8-2-9-6(5)10/h1-2H,(H,8,9,10) 

 


Linked Posts
Attached Files
MNR118-1_table.PNG
MNR118_scheme.png
mnr118-1_filter_1H.pdf
mnr118-1_filter.zip
Comments
Re: Bromination of MNR89 at the 7 position - MNR118-1 by James Cronshaw
10th April 2013 @ 16:30
it's pretty interesting that this worked. i did three experiments where i tried to get this to happen. i think they were jrc 21, 22 and 23, or something like that. i tried HBr, Br2 and NBS in fairly harsh circumstances and none of them worked. i guess the sealed tube pushed it along or something?

if i recall correctly (and i might not), the chemical shifts of this vs. the compound brominated at the 6-position are nearly identical. i had some trouble discriminating between the two, such that mat believed that an xray might be needed at the end of my thesis to prove that the bromination had happened at the desired 6-position.
Re: Bromination of MNR89 at the 7 position - MNR118-1 by Murray Robertson
11th April 2013 @ 05:41
interesting indeed, but if you look at MNR119-2 where it is the chloro, bromo compound the shifts are different to when the Br is at the 6 position. Granted, this reaction has only gone in less than 5% conversion but it is again consistent with the literature. I'll need to repeat this to get the conversion better but it is hopeful and nice to see that we should be able to make some compounds with substitution at the 7 position.