Access to Saturated Fused Pyrimidine Derivatives via a Flexible N-Vinyl Tertiary Enamide Synthesis

 

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Abstract

An array of tetrasubstituted saturated fused pyrimidines has been synthesized through two-sequential, simple, and efficient one-pot operations. The strategic utilization of the N-PMB group proved critical in the ability to construct a broad range of N-vinyl tertiary enamide starting materials. This stands as a flexible approach to functionalized pyrimidines with the capability of manipulating either ketone, acid chloride, or nitrile reaction partners.

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Spectroscopic studies and experiments with carbocation scavengers (thioanisole, triethylsilane, etc.) were unsuccessful in identifying the PMB-containing side product.

Temperature-controlled experiments were performed with a Bruker 500 MHz, Avance III spectrometer with a 5 mm Bruker PABBO cryoprobe with data collection at -70 ˚C, -40 ˚C, -20 ˚C, 0 ˚C, and 30 ˚C.

Successful formation of saturated fused pyrimidine products can also be achieved in the absence of 2-chloropyridine, although longer reaction times are required (4-72 h) and lower yields (10-15% loss) are typically obtained.

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