Patent EA-003061-B1 (EA)
Title: Method for preparing an n-[(aliphatic or aromatic)carbonyl]-2-aminoacetamide compound and a cyclyzed compound
Inventor: HULME CHRISTOPHER
IPC: C07C271/28
Filed: 1999-01-29
Abstract: 1. A method for preparing a cyclized compound, comprising the following stages: a) obtaining the compound which is N-[(aliphatic, alicyclic or aromatic group)-carbonyl)]-2-aminoacetamide compound of the formula   wherein Raa is optionally substituted aliphatic, optionally substituted alicyclic or optionally substituted aromatic group; Rb is optionally substituted aliphatic, optionally substituted alicyclic or optionally substituted aromatic group; Rca and Rcb are independently hydrogen, optionally substituted aliphatic, optionally substituted alicyclic or optionally substituted aromatic group; Rda is optionally substituted aliphatic, optionally substituted alicyclic or optionally substituted aromatic group; and Raa is substituted with a primary or secondary protected amine that upon deprotection can react with the *ab or *db carbon, or at least one of Rb, Rca or Rcb where each is at least substituted with an activated carboxylic acid group to form a 5-7 membered cyclic ring; or Rb is substituted with a primary or secondary protected amine that upon deprotection can react with the *ab or *db carbon, or at least one of Raa, Rca, or Rcb, where each is at least substituted with an activated carboxylic acid group to form a 5-7 membered cyclic ring; or Rca, and Rcb, are independently substituted with a primary or secondary protected amine that upon deprotection can react with the *ab or *db carbon, or at least one of Raa, Rb, Rca, Rcb, or Rda, where each is at least substituted with an activated carboxylic acid group to form a 5-7 membered cyclic ring; or Rda is substituted with a primary or secondary protected amine that upon deprotection can react with at least one of Rca, or Rcb, where each is at least substituted with an activated carboxylic acid to form a 5-7 membered cyclic ring, provided that when Raa is substituted with a primary or secondary protected amine that upon deprotection can react with Rb at least substituted with an activated carboxylic acid group, then Raa is other than substituted aliphatic group or substituted alicyclic group, wherein "aliphatic group" is alkyl, aralkyloxyalkyl, aralkyloxycarbonylalkyl, aralkyl, heteroaralkyl, heteroaralkyloxyalkyl, which are as determined below and which are optionally substituted, including, attached directly to solid carrier (resin) or attached to solid carrier through a linker; and residual, non-carboxyl part of natural or artificial aminoacids; "alicyclic group" is cycloalkyl, heterocyclyl, fused arylcycloalkyl, fused heteroarylcycloalkyl, fused arylheterocyclyl and fused heteroarylheterocyclyl, which are as determined below and which are optionally substituted, including, attached directly to solid carrier (resin) or attached to solid carrier through a linker; "aromatic group" represents aryl and heteroaryl cycles and comprises aryl, fused cycloalkylaryl, fused heterocyclylaryl, heteroaryl, fused cycloalkylheteroaryl, fused heterocyclylheteroaryl, which are as determined below and which are optionally substituted, including, attached directly to solid carrier (resin) or attached to solid carrier through a linker; comprising reacting the following four compounds: an carbonyl compound of formula   an amine compound of formula NH2Rb, an isonitrile compound of formula NCRda, and an acid compound of formula RaaCO2H, and b) detaching the protecting group and cyclization of said N-[(aliphatic, alicyclic or aromatic group)-carbonyl)]-2-aminoacetamide compound of formula (A) to produce the cyclized compound, selected from the group consisting of compounds represented by formulae:   wherein n = 1 or 2; m = 0 or 1; p = 2; R<1> and R<9> independently represent hydrogen, alkyl, aralkyl, aryl, fused arylcycloalkyl, fused arylheterocyclyl, cycloalkyl, heteroaralkyl, heteroaryl, fused heteroarylcycloalkyl, fused heteroarylheterocyclyl, and heterocyclyl; R<2> represents alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, fused heteroarylcycloalkyl, and fused heteroarylheterocyclyl; R<3> represents hydrogen, C1-4-alkyl, aralkyl, and heteroaralkyl; R<4> or R<5> independently represent hydrogen, alkyl, aralkyl, and heteroaralkyl; R<6>, R<7>, R<8> and R<8'> independently represent hydrogen, C1-4-alkyl; R<10> and R<11> are independently selected from hydrogen, alkyl, aralkyl and heteroaralkyl; R<14> and R<15> is independently selected from hydrogen; or, when n=1 and R<11> and R<14> are absent, R<10> and R<15>, taken together with adjacent carbon atoms, through which they are bounded, form 6-membered aryl; or, when n=1 and R<11> and R<14> are present, R<10> and R<15>, taken together with adjacent carbon atoms, through which they are bounded, form 5-7-membered cycloalkyl; or, when n=2 and adjacent R<11> and R<14> are absent, R<10> and adjacent R<15>, taken together with adjacent carbon atoms, through which they are bounded, form 6-membered aryl; R<12> is selected from alkyl, aralkyl, aryl, fused arylcycloalkyl, fused arylheterocyclyl, cycloalkyl, heteroaralkyl, heteroaryl, fused heteroarylcycloalkyl, fused heteroarylheterocyclyl and heterocyclyl; and R<16> is selected from alkyl, aralkyl, aryl, fused arylcycloalkyl, fused arylheterocyclyl, heteroaralkyl, heteroaryl, fused heteroarylcycloalkyl, and fused heteroarylheterocyclyl, wherein the above-mentioned terms have the following meaning: "alkyl" is aliphatic hydrocarbon group, which can be linear or branched and comprises from 1 to 20 carbon atoms in chain and, optionally, can be substituted with one or several "substituents for alkyl group", which can be similar or different, and comprise cycloalkyl, alkoxy, aryloxy, alkylthio, aralkylthio, arylsulphonyl, alkylsulphonyl, alkylphosphonate, heteroaralkyloxy, heterocyclyl, condensed heteroarylcycloalkyl, condensed heteroarylheterocyclyl, condensed arylcycloalkyl, condensed arylheterocyclyl, alkoxycarbonyl, aralkoxycarbonyl, heteroaralkyloxycarbonyl and Y<1>Y<2>N- and Y<1>Y<2>NCO-, wherein Y<1> and Y<2 >independently represent hydrogen or C1-4-alkyl; "aryl" is aromatic monocyclic or polycyclic nuclear system of 4-14 carbon atoms, preferably of 6-10 carbon atoms, and can be optionally substituted with one or several "substituents for cyclic system", which can be similar or different and have the meanings determined below; "aralkyl" is alkyl group, substituted with one or several aryl groups , wherein aryl and alkyl have the meanings determined above; "cycloalkyl" is non-aromatic mono- or polycyclic system of 3-10 carbon atoms and can be optionally substituted with one or several "substituents for cyclic system", which can be similar or different and have the meanings determined below; "heteroaryl" is aromatic monocyclic or polycyclic system of 5-14 carbon atoms, wherein one or several atoms in cycle(s) are heteroelements, differing from carbon, such as atoms of nitrogen, oxygen or sulphur; at that said heteroaryl can be optionally substituted with one or several "substituents for cyclic system", which can be similar or different and have the meanings determined below; "heteroaralkyl" is heteroarylalkyl group, wherein heteroaryl and alkyl have the meanings determined above; "heterocyclyl" is non-aromatic saturated monocyclic or polycyclic system of 3-10 carbon atoms, wherein one or several atoms in cycle(s) are heteroelements, differing from carbon, such as atoms of nitrogen, oxygen or sulphur; at that said heterocyclyl can be optionally substituted with one several "substituents for cyclic system", which can be similar or different and have the meanings determined below; "condensed arylcycloalkyl" is condensed aryl and cycloalkyl, having the meanings determined above, at that said condensed arylcycloalkyl can join through any capable of it atom of its cyclic system and can be optionally substituted with one or several "substituents for cyclic system", which have the meanings determined below; "condensed arylheterocyclyl" is condensed aryl and heterocyclyl, having the meanings determined above, at that said condensed arylheterocyclyl can join through any capable of it atom of its cyclic system and can be optionally substituted with one or several "substituents for cyclic system", which have the meanings determined below; "condensed heteroarylcycloalkyl" is condensed heteroaryl and cycloalkyl, having the meanings determined above, at that said condensed heteroarylcycloalkyl can join through any capable of it atom of its cyclic system and can be optionally substituted with one or several "substituents for cyclic system", which have the meanings determined below; "condensed heteroarylheterocyclyl" is condensed heteroaryl and heterocyclyl, having the meanings determined above, at that said condensed heteroarylheterocyclyl can join through any capable of it atom of its cyclic system and can be optionally substituted with one or several "substituents for cyclic system", which have the meanings determined below; "substituents for cyclic system" are substituents, attached to aromatic and non-aromatic cyclic systems, and said substituents comprise alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, halo, alkylthio, arylthio, and Y<1>Y<2>NSO2-, wherein Y<1> and Y<2 >independently represent hydrogen, or C1-4-alkyl; moreover, in case when cyclic system is saturated or partly saturated, then oxo (O=) and thioxo (S=) are also considered to be "substituents for cyclic system"; "alkoxy" represents the group alkyl-O-, wherein the alkyl group has the meanings determined above; "aralkoxy" represents the group aralkyl-O-, wherein the aralkyl group has the meanings determined above; "alkoxycarbonyl" represents the group alkyl-O-CO-, wherein the alkyl group has the meanings determined above; "aralkoxycarbonyl" represents the group aralkyl-O-CO-, wherein the aralkyl group has the meanings determined above; "alkylphosphonate" represents the group (alkyl-O)2P=O-, wherein the alkyl groups are independent from one another and have the meanings determined above; "alk