Inorganic Medicinal Chemistry

Industrial and Engineering Chemistry Indian Journal of Chemistry Indian Journal of Chemistry. Section B Organic Chemistry and Medicinal Chemistry Inorganic Chemistry... 

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

Marzilli, L. G., Dannals, R. F., Burns, H. D. "mTc radiopharmaceuticals uses, problems, potential applications in nuclear medicine, in Inorganic Chemistry in Biology and Medicine (ed. Martell, A. E.), p. 91, ACS Symp. Series 140, Washington, Amer. Chem. Soc. 1980... 

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