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10th September 2016 @ 15:17

Historically, the synthesis of pyrimethamine/Daraprim has been done in three steps, with minor variations in the conditions used for each of these transformations.

Overview of Mechanism: _.png

The literature conditions to accomplish these transformations usually include rough conditions not suited for student-run experiments. Harsh basic conditions(NaOEt in refluxing ethanol, LDA at -78 °C:) are usually used for step 1. Diazomethane has been used for the alkylation in step 2, and step 3 requires access to free guanidine prepared from guanidine hydrochloride and sodium ethoxide. The conditions historically used for step 1 and step 2 will be avoided in this experiment as they include harsh base, and highly toxic and explosive reagents. 

 

As of 2016-09-05, suitable conditions have been developped for reaction but not 2 or 3. See DP-1-1

 

Strings:

ClC1=CC=C(CC#N)C=C1

ClC1=CC=C(/C(C#N)=C(O)\CC)C=C1

ClC1=CC=C(/C(C#N)=C(OC)\CC)C=C1

ClC1=CC=C(C(C(N)=NC(N)=N2)=C2CC)C=C1

Attached Files
Overview of Mechanism: _.png