[alphahydroxy]

Hey folks,

I'm having a bit of brain freeze regarding the mechanism of an ealry step in the synthesis of benzodiazepines - can someone help me out please?!

The step is illustrated below - the conversion of 5-chloro-N-methylisatoic anhydride to 7-Chloro-1-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione using glycine and triethylamine:

Help is much appreciated!

[AWK]

you use a wrong scheme from http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/diazepam.html. The error is in 5-chloro-N-methylisatoic anhydride. See original reference:
New synthesis of diazepam by Marshall Gates
JOC 45, 1675-1681 (1980)

[alphahydroxy]

you use a wrong scheme from http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/diazepam.html. The error is in 5-chloro-N-methylisatoic anhydride. See original reference:
New synthesis of diazepam by Marshall Gates
JOC 45, 1675-1681 (1980)

Oops! You are right, of course!

For anyone who is not clear, the scheme i put up show a 1,3-dicarbonyl compound, and this should be the corresponding anhydride (i.e. the carbon in between the two carbonyls should be an oxygen).

Forgive me though - I'm still running into brainfreeze regarding the mechanism... I skimmed the paper, and it appears to give a proposed mechanism for an alternative route, but not for the step under consideration here. I'm sure this is something I should be able to work out very quickly, but I am struggling...!

Any help would be much appreciated!

[AWK]

Think about reaction of anhydride with amine, decarboxylation and then cyclization.