Synthesis of the derivatives of 6‐amino‐uracil labelled with 14 14 C

摘要

The radioactively labelled 6‐amino‐5‐nitroso‐uracil (1) and 5‐acetyl‐6‐amino‐1,3‐dimethyl‐uracil (2) were required for metabolic studies to assess their suitability as drug candidates. A common precursor for both compounds was [cyano‐ 14 C]cyanoacetic acid (6), readily prepared from potassium [ 14 C]cyanide. ACS reagents, namely, diethyl ether, acetic acid and acetic anhydride, had to be rigorously repurified to achieve a successful synthesis of 14 C‐labelled compounds on a tenth‐of‐a‐milligramme scale. 6‐Amino‐5‐nitroso‐[6‐ 14 C]uracil (1‐ 14 C) (0.55?mCi) was prepared with radiochemical purity??98% and specific activity (SA)?=?55.6?mCi/mmol. 5‐Acetyl‐6‐amino‐1,3‐dimethyl‐[6‐ 14 C]uracil (2‐ 14 C) (8?mCi) was prepared with radiochemical purity??97% and SA?=?55.6?mCi/mmol. It has been shown that a SA assay can be made from standard 13 C NMR spectra, thus avoiding the need to perform lengthier inverse‐gated 13 C NMR experiments.