METHODS OF SYNTHESIS OF 4-CYANO-4-(SUBSTITUTED INDAZOLE)-CYCLOHEXANE CARBOXYLIC ACID ESTERS USED AS INHIBITORS OF PHOSPHODIESTERASE 4 (PDE 4) AND INTERMEDIATE COMPOUNDS FOR THEIR SYNTHESIS Russian patent published in 2002 - IPC

FIELD: organic chemistry, biochemistry. SUBSTANCE: invention proposes two methods of synthesis of compounds of the formula (I) where R_a means C₁-C₆-alkyl; R means a group -(CH₂)_n(C₃-C₇)-cycloalkyl where n = 0,1; R₁ means C₁-C₆-alkyl, hydrogen atom. The first method involves treatment of compound of the formula (Ia) with alcohol of the formula R_aOH where R_a has said values and with acid HX taken among a group including hydrobromic and hydrochloric acid that provides acidic conditions that results to formation of salt of the corresponding imidate of the formula (Ic) and hydrolysis of said compound of the formula (Ic) to yield a compound of the formula (I). The second method involves treatment of the compound (Id) with hydrazine of the formula R-NH-NH_2/ (Ie) to yield a compound of the formula (If) , heating a compound of the formula (If) to yield indazole of the formula (Ig) , treatment of indazole of the formula (Ig) with cyclohexane-1,4-carbodinitrile of the formula (Ih) to yield the compound of the formula (Ia) that is subjected for treatment in correspondence with the said first method. In compounds of formulas (Ic)-(Ig) corresponding substitutes have values determined above for the formula (I). Except for, invention proposes intermediate compounds of formulas and where substitutes have values that correspond to analogues substitutes in the formula (I). EFFECT: improved method of synthesis of compounds of formula (I) as inhibitors of phosphodiesterase 4 (PDE 4). 10 cl, 5 ex