Hepatitis C drug candidate

The development of the key intermediate, 5-(2-methoxy-4-nitrophenyl)oxazole (25), in the preparation of the hepatitis C drug candidate, VX-497, utilizes a van Leusen reaction of aldehyde 24 with TosMIC. ... 

Tosylmethylisocyanide (TosMIC) reacts with aldehydes via a [3+2] pathway, under basic conditions, to give 5-substituted oxazoles. In one example, the resulting oxazole product was used in the synthesis of a key intermediate for the hepatitis C drug candidate VX-497 (Scheme 56) <20020PD677>. K2CO3 is usually the base of choice for this reaction since stronger bases such as KO/-Bu lead to a cyanide product. 

Modification other atoms or groups. Besides fluorine atoms, other atoms (such as C, N and O) and groups are also used to produce novel sugar-modified nucleoside monophosphates. 2-C-Methyl nucleosides are potential candidates with activity against Hepatitis C virus. Leisvuori et al ° prepared 3,5-cyclic phosphates (25a) and 3,5-cyclic thiophosphates (25h) of 2-C-methyl ribonucleosides as potential antiviral drugs. 

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