R. Lin, Rhys Salter, Yong-Xiang Gong
Apr 1, 2009
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Journal
Journal of Labelled Compounds and Radiopharmaceuticals
Abstract
5-(Hydroxymethyl)thiazole is a versatile building block for many biologically active compounds. A rapid and efficient four-step synthesis of its stable isotope labeled counterpart with four 13 C and four deuterium atoms in 32% total yield is reported. Condensation of [ 13 C 2 ]-chloro acetic acid with [ 13 C]-thiourea gave [ 13 C 3 ]-2,4-thiazolidinedione. Reaction of [ 13 C 3 ]-2,4-thiazolidinedione with phosphorus oxybromide and [ 13 C, D]-DMF (Me 2 N 13 CDO) produced [ 13 C 4 , D]-2,4-dibromothiazole-5-carboxaldehyde. The resultant aldehyde was then reduced by sodium borodeuteride to [ 13 C 4 , D 2 ]-(2,4-dibromothiazol-5-yl)-methanol. Catalytic deuteration of [ 13 C 4 , D 2 ]-(2,4-dibromo-thiazol-5-yl)-methanol by palladium black with deuterium gas at 1 atm pressure and room temperature produced completely de-brominated [ 13 C 4 , D 4 ]-5-(hydroxymethyl)thiazole. De-bromination of the 2,4-dibromothiazole by the catalysis of palladium black provides a simple and convenient synthetic method for the stable isotope labeled and potentially radioactive isotope labeled thiazole compounds.