Verfahren zur Herstellung von neuen α-Alkyl-thyroninen

摘要

Novel compounds of the general formula (wherein R1 represents a C1- 6 alkyl radical, R2 represents an NH2 or acylated NH2 group, and R3, R4 and R5, which may be the same or different, represent H or I atoms) are prepared by (a) reacting a compound of the general formula (wherein R6 and R7 jointly represent -NH-CO-NH- or R6 represents OH or etherified OH and R7 represents NH2 or acylated NH2) with an acid of the general formula at substantially neutral pH under anaerobic or aerobic conditions at temperatures below 100 DEG C. and, if necessary, converting R6 and R7 to OH and NH2, or (b) reacting a compound II (but in which R7 is not NH2) with a compound of the general formula (wherein R9 represents in alkyl radical and An an anion) in a solvent in the presence of a basic substance, removing the solvent, removing R9 by acid hydrolysis, hydrolysing the hydantoin (when R6 + R7 = -NH-CO-NH-) by warming with dilute aqueous alkaline or mineral acid solutions, and mono- or di-iodinating the product, preferably in alkaline solution, or (c) reacting an activated ester of a compound of the general formula (wherein R6 and R8 jointly represent -NH-CO-NH- or R6 represents OH or etherified OH and R8 represents an acylamino group) with a compound of the general formula in the presence of a solvent and/or a base, replacing the NO2 groups by R3 and R4 via NH2 and diazo groups and completing the process as in (b), omitting the iodination step when using a compound XI. The products may be converted into salts with inorganic or organic acids or bases, and a free NH2 group in the products may be acylated. The preparation of the following starting materials and intermediates is described: 5 - (31 - iodo - p - hydroxybenzyl) - 5 - methylhydantoin, 5 - (31,51 - dinitro -, - diamino - and - diiodo - 41 - p - methoxyphenoxybenzyl) - 5 - methylhydantoin, 5 - (31,51 - diiodo - 41 - p-hydroxyphenoxybenzyl) - 5 - methylhydantoin, and 3,5 - diiodo - a - methylthyromine (and its sodium salt). Reference has been directed by the Comptroller to Specification 1,047,082.