Raltegravir (free base) Selective N- v’s O- alkylation of an amide can be challenging and somewhat unpredictable- the outcome being highly dependent on the structure of the substrate. A good example of this is the N-methylated pyrimidone intermediate (5) en route to Merck’s antiretroviral drug Raltegravir.1 Direct methylation of amide (4) (Figure 1) using MeI gives significant

The concept of borrowing hydrogen (also known as Hydrogen auto-transfer) is a useful concept which combines transfer hydrogenation with other reactions to produce more complex molecules, exemplified by the alkylation of amines with alcohols and the reaction of benzyl alcohol with acetophenone to give 1,3 diphenylpropanone.   For the process chemist these processes seem to be