ES422413A1 - Unsymmetrically substituted bis-chromones - Google Patents

Abstract

A procedure for preparing benzopyran derivatives of formula I **(See formula)** wherein R1, R2, R3, R4, R5 and R6, which may be the same or different, individually represent hydrogen, halogen, hydroxyl, C1 to C6 alcohol, C1 to C6 alkoxy, C1 to C6 alkenyl, the alcohol and alkoxy groups optionally substituted by hydroxyl, C1 to C6 alkoxy, halogen or phenyl, X is a hydrocarbon group containing from 2 to 10 carbon atoms, which is optionally interrupted by an oxygen atom, and/or substituted by a group -OH, Ra and Rb are different, and are selected from the groups -COOH, -CONHOH and **(See formula)** or a pharmaceutically acceptable derivative thereof, comprising: (a) reacting a compound of formula VI **(See formula)** or an ester thereof, with a compound of formula VII **(See formula)** formulas in which R1, R2, R3, R4, R5, R6, Ra and Rb are as defined above, and X represents hydrogen or a reactive metal when Z represents a group Xb, and when X represents hydrogen or a reactive metal, Y represents a group Xb, and Xb represents a hydrocarbon group containing from 2 to 10 carbon atoms, which is optionally interrupted by an oxygen atom, and which carries an epoxide group or an anion-forming group, which by reaction with hydrogen or a reactive metal produces a group X; (b) producing a compound of formula Ib **(See formula)** wherein R1, R2, R3, R4, R5, R6 Rb and X are as defined above, (i) reacting a compound of formula VIII **(See formula)** wherein R1, R2, R3, R4, R5, R6, X and Rb are as defined above, with an azide, in a solvent that is inert under the reaction conditions, or (ii) separating an R11 group from a compound of formula III or IV **(See formula)** Formulas III and IV in which R1, R2, R3, R4, R5, R6, Rb and X are as defined above, and R11 represents a group that can be replaced by hydrogen; (c) producing a compound of formula Ia **(See formula)** wherein R1, R2, R3, R4, R5, R6, Rb and X are as defined above, selectively hydrolyzing a compound of formula IX **(See formula)** wherein R1, R2, R3, R4, R5, R6, Rb and X are as defined above, and D represents a group hydrolyzable to a -COOH group, or (d) producing a compound of formula Ic **(See formula)** wherein R1, R2, R3, R4, R5, R6, Rb and X are as defined above, reacting a monoester, -anhydride or -acid halide of a compound of formula X **(See formula)** wherein R1, R2, R3, R4, R5, R6 and X are as defined above, and Rc is a -COOH or (see formula), with hydroxylamine, and, if necessary or desired, converting the compound of formula I into a pharmaceutically acceptable derivative thereof. (Machine-translation by Google Translate, not legally binding)