METHOD FOR PREPARING NO-DONOR COMPOUNDS, SUCH AS NO-DONOR DICLOFENAC Russian patent published in 2008 - IPC C07C201/00 C07C211/55 C07C309/63 A61K31/216 A61P29/00 

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to a novel method for synthesis of NO-donor compounds of the formula (IV): ML_T1A_T2-COO-X-ONO_n (IV). Method involves carrying out the following steps: (1) reaction of compound of the formula (I): ML_T1A_T2-COOH (I) with compound of the formula: HO-X-OH using acid or dehydrogenating agent and the first solvent followed by optional purification by extraction or crystallization in order to obtain compound of the formula: ML_T1A_T2-COO-X-OH (II); (2) reaction of compound of the formula (II) with compound of the formula: RSO₂Cl using the second solvent, base and, optionally, catalyst followed by purification by extraction and crystallization in order to obtain compound of the formula (III): ML_T1A_T2-COO-X-OSO₂R (III); (3) reaction of compound of the formula (III) with compound of the formula: Y-NO₃ using the third solvent and, optionally, catalyst followed by optional crystallization for preparing compound of the formula (IV): ML_T1A_T2-COO-X-ONO_n (IV) wherein group ML_T1A_T2 is chosen from group consisting of the following substances:

and wherein X is chosen from group consisting of linear -(CH₂)_w1- wherein w1 = 2-10; -(CH₂-CH₂O)₂-CH₂-CH₂- and -CH₂-C₆H₄-CH₂-; R is chosen from group consisting of (C₁-C₈)-alkyl, phenyl, phenylmethyl, (C₁-C₄)-alkylphenyl, halogenphenyl, nitrophenyl, acetylaminophenyl, halogen atom, -CF₃ and n-C₄F₉; Y-NO₃ represents lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate, iron nitrate, zinc nitrate and tetraalkyl ammonium nitrate wherein alkyl represents (C₁-C₁₈)-alkyl that can be linear or branched, and their mixture; m = 2, and under condition that when ML_T1A_T2-COOH represents naproxen then X doesn't mean -(CH₂)₄. Also, invention relates to using a method for synthesis of compounds of formulas (IVa), (IVb), (IVc) and (IVd) given in the invention description, their novel intermediate compounds of formulas (IIIa), (IIIb), (IIIc) and (IIId) given in the invention description, crystalline form of 2-[2-(nitrooxy)ethoxy]ethyl{2-[(2,6-dichlorophenyl)amino]phenyl}acetate and to a method for its synthesis, and its using for preparing a drug used in pain and/or inflammation treatment, using compounds of the formula (III) as intermediate compounds. Also, invention relates to using intermediate compounds of formulas (IIIa), (IIIb), (IIIc) and (IIId) used for synthesis of compounds of formulas (IVa), (IVb), (IVc) and (IVd). Invention provides a novel method for synthesis of compounds of the formula (IV).

EFFECT: improved method of synthesis.

32 cl, 2 tbl, 5 ex