PROCESSES FOR PREPARING MACROLIDES AND KETOLIDES AND INTERMEDIATES THEREFOR Russian patent published in 2017 - IPC C07H1/00 C07H17/08 A61K31/70 

FIELD: chemistry.

SUBSTANCE: invention described herein relates to methods of obtaining macrolide antibacterial agents. In particular, invention relates to methods for preparing macrolides and ketolides from erythromycin A. Method of producing a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is hydrogen or acyl; X is H; Y is OR⁷; where R⁷ is cladinose, alkyl or arylalkyl, or acyl or C(O)NR⁸R⁹, where each R⁸ and R⁹ is independently selected from a group, consisting of hydrogen, hydroxy, alkyl, alkoxy, aryl, aryalkyl, dimethylaminoalkyl, acyl, sulphonyl, ureido and carbamoyl; or R⁸ and R⁹ together with nitrogen atom attached thereto form a heterocycle; or X and Y together with a carbon atom attached thereto form a carbonyl; V is C(O), C(=NR¹¹), CH(NR¹², R¹³) or N(R¹⁴)CH₂; where N(R¹⁴) is bonded to C-10 carbon atom; where R¹¹ is a hydroxy or alkoxy; each R¹² and R¹³ is independently selected from a group consisting of hydrogen, hydroxy, alkyl, alkoxy, aryl, aryalkyl, dimethylaminoalkyl, acyl, sulphonyl, ureido and carbamoyl; R¹⁴ is hydrogen, hydroxy, alkyl, alkoxy, aryl, arylalkyl, dimethylaminoalkyl, acyl, sulphonyl, ureido or carbamoyl; W denotes H, F, Cl, Br, I or OH; A is CH₂, C(O), C(O)O, C(O)NH, S(O)₂, S(O)₂NH or C(O)NHS(O)₂; B is (CH₂)_n, where n is an integer from 0 to 10; or unsaturated carbon chain, containing from 2 to 10 carbon atoms; and C is hydrogen, hydroxy, alkyl, alkoxy, aryl, arylalkyl, acyl, acyloxy, sulphonyl, ureido or carbamoyl; where alkyl independently in each case represents a C₁-C₃₀ alkyl; aryl in each case is independently selected from a group consisting of phenyl, optionally substituted amino group, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, quinolinyl, quinazolinyl, quinoxalinyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, benzisoxazolyl, benzisothiazolyl; acyl in each case is independently selected from a group consisting of C(O)alkyl and C(O)aryl, C(O)arylalkyl; involves (b) bringing a compound of formula (IV) or acid addition salt thereof, where R is a spatially hindered acyl group; and Q is 2-methoxy-2-propyl, 1-methoxycyclohexyl or tropyl; into contact with a methylating agent to obtain a compound of formula (V) or acid addition salt thereof; and (c) bringing compound of formula (V) or acid addition salt thereof into contact with deoximating agent to obtain a compound of formula (II) or acid addition salt thereof; and conversion of compound of formula (II) or acid addition salt thereof into a compound of formula (I) or a pharmaceutically acceptable salt thereof.

EFFECT: production of antibacterial agents.

32 cl, 9 ex