EP3625219A1 - Procédé pour produire des imidazolylcarboxyamides substitués - Google Patents

Procédé pour produire des imidazolylcarboxyamides substitués

Info

Publication number
EP3625219A1
EP3625219A1 EP18725437.0A EP18725437A EP3625219A1 EP 3625219 A1 EP3625219 A1 EP 3625219A1 EP 18725437 A EP18725437 A EP 18725437A EP 3625219 A1 EP3625219 A1 EP 3625219A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
methyl
cyano
ethyl
substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP18725437.0A
Other languages
German (de)
English (en)
Inventor
Marc Mosrin
Matthieu WILLOT
Johannes-Rudolf Jansen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer AG
Original Assignee
Bayer AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer AG filed Critical Bayer AG
Publication of EP3625219A1 publication Critical patent/EP3625219A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a process for the preparation of substituted imidazolylcarboxyamides of the formula (II)
  • Substituted imidazolylcarboxyamides of the formula (II) are of great industrial importance for the pharmaceutical and agrochemical industries and are, for example, important intermediates for compounds which, inter alia, are active as pesticides or are themselves active inter alia as pesticides.
  • the regioselective introduction of the substituent X on compounds of the formula (II) represents a great challenge. This is particularly difficult due to the amide group adjacent to the imidazolyl radical. This usually directs substituents preferentially in the undesired ortho position. In addition, the amide group generally activates the ortho position on the likewise adjacent pyridyl radical. Thus, targeted substitution at the desired position is difficult.
  • imidazolylcarboxamides of the formula (II) which are substituted in a process using a zinc metal organic base can be prepared advantageously, in particular also with high regio- and chemoselectivity and good yield.
  • the present invention accordingly provides a process for the preparation of compounds of the formula (II)
  • A represents a radical selected from hydrogen, optionally mono- or polysubstituted independently of one another by halogen, Ci-C i-alkoxy, Ci-C4-alkyl-S (0) m - or cyano-substituted Ci- C6 alkyl, C3-C6 alkenyl or C3-C6-alkynyl and optionally mono- or disubstituted independently of one another by halogen, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C 4 alkoxy or cyano substituted C3-C6-cycloalkyl, and is optionally mono- to disubstituted independently 4 haloalkyl, Ci-C 4 -alkoxy or cyano, straight or branched C3-C8-cycloalkyl-Ci-C4-alkyl substituted by halogen, Ci-C4-alkyl, Ci-C,
  • V is a radical from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and cyano,
  • T oxygen or a pair of electrons
  • W is a radical from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and cyano,
  • Y is a radical selected from hydrogen, cyano, optionally mono- or polysubstituted independently of one another by halogen, Ci-C 4 alkoxy, Ci-C 4 alkyl-S (0) m - or cyano-substituted Ci-C6-alkyl, C3 C6-alkenyl or C3-C6-alkynyl, optionally mono- or disubstituted independently of one another by halogen, Ci-C4-alkyl, Ci-C 4 haloalkyl, C 1 -C 4 - alkoxy or cyano-substituted C3-Cs-cycloalkyl, optionally mono- to disubstituted independently of one another by O, S (0) m , CO or NR 2 interrupted and optionally mono- to disubstituted independently of one another by halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C
  • C4-alkyl and which is optionally mono- to trisubstituted independently of one another by halogen, Ci- C4 alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, Ci-C 4 alkyl-S (0) m -, Ci- C 4 haloalkoxy, C 1 -C 4 -haloalkyl-S (0) m -, nitro or cyano substituted arylalkyl or hetarylalkyl, m is a number 0, 1 or 2, R 2 is a radical from the series hydrogen, optionally mono- to polysubstituted by C 1 -C 4 -alkoxy or C 1 -C 4 -alkyl-S (0) m -substituted C 1 -C 5 -alkyl, C 3 -C 8 -alkenyl or C 5 -C 8 -alkynyl, optionally mono- to polysubstituted by O or S
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , simply up to five times by fluorine, chlorine and bromine and simply up to three times by methoxy, ethoxy, Methyl-S (0) n -, ethyl-S (0) n - and cyano-substituted C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl, optionally monosubstituted to trisubstituted independently of one another by halogen, NL 2 L 3 , nitro,
  • L 1 is optionally mono- to polysubstituted independently of one another by halogen, cyano, C 1 -C 4 -alkoxy or C 1 -C 4 -alkyl-S (O) n -, substituted C 1 -C 6 -alkyl, C 2 -C -alkenyl or C 2 -C 8 Alkynyl, optionally monosubstituted by O or S (0) n , interrupted and optionally monosubstituted or disubstituted independently of one another by halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy or cyano-substituted Cs-Cs -Cycloalkyl, optionally substituted by O or S (0) n , interrupted and optionally mono- to disubstituted independently of one another by halogen, Ci-C 4 alkyl, Ci-C 4 -hal
  • L 2 and L 3 together form an optionally monosubstituted to trisubstituted by halogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy substituted four to seven membered aliphatic ring optionally containing an N, S or O atom,
  • R 4 is a radical selected from the group consisting of hydrogen, optionally mono- to trisubstituted independently of one another by halogen, C 1 -C 4 -alkoxy and C 1 -C 4 -alkyl-S (O) n -substituted C 1 -C 8 -alkyl, C 3 -C 8 -alkenyl and C3-Cs-alkynyl, optionally mono- to disubstituted independently of one another by halogen, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy and cyano-substituted C3-C8-cycloalkyl and C3-C8-cycloalkyl-Ci-C4 Alkyl, optionally monosubstituted to trisubstituted independently of one another by halogen, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, Ci
  • R a and R b together form a - (CH 2) 4 -, - (CLL s - or - (CH 2) 20 (CH 2) 2-Gru e, each of these groups optionally by 1, 2, 3 or 4 R d - Radicals may be substituted and R d is selected from the group consisting of methyl, ethyl, n-propyl and i-propyl, is converted to a compound of formula (IIIa) or (IIIb),
  • the compounds of the formulas (I), (II), (IIIa) and (IIIb) can also be present as salts in the process according to the invention.
  • the compounds of the formula (IIIa), (IIIb) and the zinc organometallic base may also be complexed with salts, the salts preferably being alkali metal or alkaline earth metal halides, preferably lithium chloride and / or magnesium chloride and more preferably lithium chloride ,
  • A represents a radical selected from hydrogen, optionally mono- to pentasubstituted independently of one another by fluorine, chlorine, bromine, methoxy, ethoxy, methyl-S (0) m -, ethyl-S (0) m - or cyano-substituted Ci-C6- Alkyl, C3-C6-alkenyl or C3-C6-alkynyl, optionally mono- to disubstituted independently of one another by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6-cycloalkyl and optionally mono- to disubstituted independently represents straight-chain or branched C 3 -C 6 -cycloalkyl-C 1 -C 2 -alkyl substituted by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, me
  • V is a radical selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy and cyano,
  • T oxygen or a pair of electrons
  • W is a radical from the series consisting of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy and cyano,
  • Y is a radical selected from the group consisting of hydrogen, cyano, optionally monosubstituted to pentane-independent Ci-C independently of one another by fluorine, chlorine, bromine, methoxy, ethoxy, methyl-S (0) m -, ethyl-S (0) m - or cyano i-alkyl, C3-C4-alkenyl or C3-C4-alkynyl optionally mono- or disubstituted independently by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6 cycloalkyl and optionally mono- to disubstituted independently of one another by O, S (0) m , CO or NR 2 interrupted and optionally mono- to disubstituted independently of one another by fluorine, chlorine, bromine, methyl, ethyl, trifluor
  • R 2 is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted by C 1 -C 6 -alkyl, independently of one another by fluorine, chlorine, bromine, methoxy, ethoxy, methylS (0) m - or ethylS (0) m - , C3-C6 alkenyl or C3-C6 alkynyl, optionally simply by O.
  • - or - S (0) m interrupted and, optionally mono- or disubstituted independently of one another optionally monosubstituted by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6-cycloalkyl, by O or S (0) m , straight-chain or branched C3-C6-cycloalkyl-Ci-C 2 -alkyl, optionally monosubstituted or disubstituted, independently of one another by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano, optionally once or twice independently of one another by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, methyl-S (0) m -, ethyl
  • L 1 is a radical from the series optionally mono- to quintuply independently of one another by fluorine, chlorine, bromine, methoxy, ethoxy or cyano-substituted C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl or C 3 -C 6 -alkynyl and optionally mono- to disubstituted independently C 3 -C 6 -cycloalkyl which is unsubstituted or substituted by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano, independently of one another by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, Ethoxy, methyl-S (0) n -, ethyl-S (0) n -, difluoromethoxy, trifluoromethoxy, trifluoromethyl-S
  • L 2 is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted independently of one another by fluorine or chlorine, substituted C 1 -C -alkyl, C 3 -C 4 -alkenyl or C 3 -C 4 -alkynyl, optionally mono- or disubstituted independently of one another by fluorine, Chloro, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6-cycloalkyl or optionally mono- to trisubstituted independently of one another by fluorine, chlorine, methoxy or ethoxy-substituted Ci-C4-alkylcarbonyl or Ci-C4-alkoxycarbonyl and optionally mono- to disubstituted independently of one another by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoro
  • L 3 is a radical from the series hydrogen, optionally monosubstituted to trisubstituted independently of one another by halogen methoxy, ethoxy, n- or iPropoxy or methyl-S (0) n -, substituted C 1 -C 4 -alkyl, C 3 -C 6 -alkenyl, C 3 C6-alkynyl or Ci-C4-alkoxy, optionally mono- to disubstituted independently of one another by fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6-cycloalkyl, or C3-C6-cycloalkyl-Ci-C4 alkyl, optionally mono- to disubstituted independently of one another, by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, eth
  • L 2 and L 3 together form an optionally mono- to disubstituted by fluorine chlorine, bromine, methyl, ethyl, methoxy or ethoxy substituted four to six membered aliphatic ring optionally containing an N, S or O atom and n is a number 0, 1 or 2 stands and
  • R c is -O-pivaloyl, chlorine, bromine or iodine.
  • Q is oxygen or sulfur
  • A is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted independently of one another by fluorine, methoxy, ethoxy or cyano, methyl, ethyl, propyl, allyl, propargyl, cyclopropyl or cyclopropylmethyl,
  • V is a radical selected from the group consisting of hydrogen, fluorine, chlorine, methyl and cyano
  • T is oxygen or an electron pair
  • W is a radical from the series hydrogen, fluorine, chlorine, bromine.
  • Y is a radical from the group consisting of hydrogen, benzyl and optionally mono- to trisubstituted independently of one another by fluorine, methoxy, ethoxy or cyano-substituted methyl, ethyl,
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine and bromine and / or simply by methoxy , Ethoxy, methylsulfanyl, ethylsulfanyl, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl or cyano-substituted vinyl, allyl, methallyl,
  • Triazol-4-yl substituted straight-chain or branched aryl-Ci-C i-alkyl or hetaryl-Ci-C i- alkyl, wherein
  • L 1 represents a radical from the series, where appropriate, monosubstituted to trisubstituted by C 1 -C 6 -alkyl which is unsubstituted or substituted by fluorine, chlorine, bromine, methoxy, ethoxy or cyano, optionally monosubstituted to disubstituted by fluorine, chlorine, bromine, methyl, ethyl, - -
  • L 2 is a radical from the series hydrogen, optionally monosubstituted to trisubstituted by fluorine, chlorine, methoxy or ethoxy substituted substituted Ci-C i-alkyl, Ci-C i-alkylsulfonyl, C3-C6-cycloalkylsulfonyl, Ci-C i -Alkylcarbonyl or Ci-C i -alkoxycarbonyl and optionally mono- to trisubstituted independently of each other by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy or ethoxy-substituted arylmethoxycarbonyl,
  • L 3 is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted independently of one another by halogen, hydroxyl, methoxy, ethoxy, methoxycarbonyl, ethoxycarbonyl or cyano-substituted C 1 -C -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl or Ci-C i-alkoxy, optionally mono- to disubstituted independently of one another by fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6-cycloalkyl or C3-C6-cycloalkyl-Ci-C i-alkyl, optionally monosubstituted or disubstituted phenyl independently of one another by fluorine, chlorine, bromine, methyl, ethy
  • L 2 and L 3 together form an optionally mono- to disubstituted by fluorine chlorine, bromine, methyl, ethyl, methoxy or ethoxy substituted four to six membered aliphatic ring optionally containing an N, S or O atom and n is a number 0, 1 or 2 stands and
  • R c is -O-pivaloyl, chlorine, bromine or iodine.
  • Q is oxygen or sulfur
  • - represents a radical from the group consisting of hydrogen, methyl, ethyl, propyl, difluoroethyl, trifluoroethyl, methoxymethyl, ethoxymethyl, cyanomethyl, allyl, propargyl, cyclopropyl or cyclopropylmethyl
  • L 1 is a radical from the series methyl, ethyl, n- or iso-propyl, 1-cyano-1-methylethyl or cyclopropyl,
  • L 2 is a radical selected from the group consisting of hydrogen, methyl, ethyl, methylsulfonyl, cyclopropylsulfonyl, methoxycarbonyl, ethoxycarbonyl, 2-methoxyethoxycarbonyl, n-, iso, sec- or t-butoxycarbonyl,
  • L 3 is a radical from the series of hydrogen, methyl, ethyl, n- or iso-propyl, n-, iso, sec- or tert.
  • L 2 and L 3 together represent (CH 2 ) 5 , (CH 2 ) 4 , (CH 2 ) 3 or (CH 2 ) 20 (CH 2 ) 2 and n is a number 0, 1 or 2 and represents chlorine , Bromine or iodine. - -
  • A is a radical from the series consisting of hydrogen, methyl, ethyl and cyclopropyl and is preferably methyl or ethyl,
  • V is hydrogen
  • T is oxygen or an electron pair, preferably an electron pair
  • W is a radical from the series consisting of hydrogen, methyl, fluorine, chlorine and bromine and is preferably hydrogen,
  • Y is methyl or ethyl
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine and bromine and / or simply by methoxy , Ethoxy, methylsulfanyl, ethylsulfanyl, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl or cyano-substituted vinyl, allyl, methallyl, 2-butenyl, propargyl, ethynyl and 2-butynyl, optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine, bromine, methyl, Ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, methyl-S (O
  • L 1 is a radical from the series methyl, ethyl, n- or iso-propyl, 1-cyano-1-methylethyl or cyclopropyl,
  • L 2 is a radical from the series consisting of hydrogen, methyl, ethyl, methylsulfonyl, or cyclopropylsulfonyl,
  • L 3 is a radical from the series hydrogen, methyl, ethyl, iso-propyl, iso-butyl, tert. Butyl, 2,2,2-trifluoroethyl, 2-hydroxyethyl, 2-methoxyethyl, cyanomethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, cyclopropyl, 1-cyano-cyclopropyl, cyclopentyl, cyclopropylmethyl, methoxy, ethoxy, phenyl, pyrid-3-yl, phenylmethyl, 1 - Phenyl-2-hydroxyethyl, or L 2 and L 3 together are (CH 2 ) 5 , (CH 2 ) 4 , (CH 2 ) 3 or (CH 2 ) 2 O (CH 2 ) 2 and n is a number 0, 1 or 2 and is chlorine or bromine, preferably chlorine.
  • R c is chlorine or bromine and A, Q, T, V, Y, X and W have the meaning according to embodiment 1 or embodiment 2 or Embodiment 3 or Embodiment 4 or Embodiment 5.
  • R c is chlorine and A, Q, T, V, Y, X and W have the meaning according to embodiment 1 or embodiment 2 or embodiment 3 or Embodiment 4.
  • A is a radical from the series methyl or ethyl, - -
  • Y is methyl or ethyl
  • R c for chlorine and X has the meaning according to embodiment 1 or embodiment 2 or embodiment 3 or embodiment 4 or embodiment 5. (embodiment 14)
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , simply up to five times by fluorine, chlorine and bromine and simply up to three times by methoxy, ethoxy, Methyl-S (0) n -, ethyl-S (0) n - and cyano-substituted C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl, optionally monosubstituted to trisubstituted independently of one another by halogen, NL 2 L 3 , nitro, cyano, Ci-C 4 alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, Ci-C 4 alkyl-S (0) n -, C1-C4 haloalkoxy, Ci-C 4 haloalkyl-S ( 0) n -, Ci-C 4 -
  • L 1 is optionally mono- to polysubstituted independently of one another by halogen, cyano, C 1 -C 4 -alkoxy or C 1 -C 4 -alkyl-S (O) n -, substituted C 1 -C 6 -alkyl, C 2 -C -alkenyl or C 2 -C 8 Alkynyl, optionally monosubstituted by O or S (0) n , interrupted and optionally monosubstituted or disubstituted independently of one another by halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy or cyano-substituted Cs-Cs Cycloalkyl optionally substituted by O or S (O) n , - - interrupted and optionally mono- to disubstituted independently by halogen, Ci-C i-alkyl, Ci-C i -
  • C3-C8-alkenyl and Cs-Cs-alkynyl optionally mono- to disubstituted independently of one another by halogen, Ci-C i-alkyl, Ci-C i -haloalkyl, Ci-C4-alkoxy and cyano-substituted C3-C8-cycloalkyl and C3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, optionally monosubstituted to trisubstituted independently of one another, by halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkyl-S (O) n - , Ci-C4-haloalkoxy, Ci-C4-haloalkyl-S (0) n -, nitro and cyano-substituted aryl and
  • Hetaryl which is optionally mono- to trisubstituted independently of one another by halogen, C1-C4 alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, Ci-C 4 alkyl-S (0) n -, C 4 - Haloalkoxy, C1-C4-haloalkyl-S (0) n -, nitro and cyano, straight-chain or branched aryl-C 1 -C 4 -alkyl and hetaryl-C 1 -C 4 -alkyl and n is a number 0, 1 or 2 and A, Q, V, W, Y, T and R ° have the meaning according to Embodiment 2 or Embodiment 3 or Embodiment 4 or Embodiment 5. (Embodiment 15)
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , optionally monosubstituted to pentavalent by halogen and monosubstituted to C 1 -C 4 alkoxy, C 1 C4-alkyl-S (0) n - and cyano-substituted C2-Cg-alkenyl or C2-Cg-alkynyl, optionally monosubstituted to trisubstituted independently of one another by halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, ci C 4 alkoxy, Ci-C 4 alkyl-S (0) n -, Ci-C4-haloalkoxy, C1-C4 haloalkyl-S (0) n -, Ci-C4-alkylcarboxy, NL 2 L 3, Nitro, cyano or optionally mono
  • Cyano substituted aryl or hetaryl substituted aryl or hetaryl or for an aryl or hetaryl ring which has attached to two adjacent ring positions a consisting of one or two heteroatoms from the series N, S or O and one or two carbon atoms and this case a heteroaromatic or given optionally partially unsaturated heterocyclic ring which and optionally one to three times independently by halogen, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, Ci-C 4 alkyl-S (0) n - , Ci-C4-haloalkoxy, C1-C4 haloalkyl-S (0) n -, Ci-C4-alkylcarboxy, NL 2 L 3, nitro, cyano or optionally mono- to trisubstituted independently of one another by halogen, Ci-C4-alkyl , Ci-C4-haloalkyl, C
  • L 1 is a radical from the series optionally mono- to quintuply independently of one another by fluorine, chlorine, bromine, methoxy, ethoxy or cyano-substituted C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl or C 3 -C 6 -alkynyl and optionally mono- to disubstituted independently C 3 -C 6 -cycloalkyl which is unsubstituted or substituted by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano, independently of one another by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, Ethoxy, methyl-S (0) n -, ethyl-S (0) n -, difluoromethoxy, trifluoromethoxy, trifluoromethyl-S
  • L 2 is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted independently of one another by fluorine or chlorine, substituted C 1 -C 18 -alkyl, C 3 -C 4 -alkenyl or C 3 -C 4 -alkynyl, optionally mono- or di-independently of one another fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano-substituted C3-C6-cycloalkyl or represents optionally mono- to trisubstituted independently of one another by fluorine, chlorine, methoxy or ethoxy-substituted Ci-C4-alkylcarbonyl or Ci-C 4 - Alkoxycarbonyl and optionally mono- to disubstituted independently of one another by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl,
  • L 3 is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted independently of one another by halogen methoxy, ethoxy, n- or ipropoxy or methyl-S (0) n -, substituted C 1 -C 4 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl or C 1 -C 4 -alkoxy, C 3 -C 6 -cycloalkyl optionally substituted once to twice independently of one another by fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano, or C 3 -C 6 -cycloalkyl-Ci C 4 alkyl, optionally mono- to disubstituted independently of one another by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, e
  • Difluoroethyl-S (0) n Difluoroethyl-S (0) n, trifluoroethyl-S (0) n -, nitro or cyano, straight-chain or branched phenyl-Ci-C2-alkyl or pyridyl-Ci-C2-alkyl, or
  • L 2 and L 3 together form an optionally mono- to disubstituted by fluorine chlorine, bromine, methyl, ethyl, methoxy or ethoxy substituted four to six membered aliphatic ring optionally containing an N, S or O atom and n is a number 0, 1 or 2 and A, Q, V, W, Y, T and R c have the meaning according to embodiment 1 or embodiment 3 or embodiment 4 or embodiment 5. (embodiment 16)
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine and bromine and / or simply by methoxy , Ethoxy, methylsulfanyl, ethylsulfanyl, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl or cyano-substituted vinyl, allyl, methallyl, 2-butenyl, propargyl, ethynyl and 2-butynyl, optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine, bromine, methyl, Ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, methyl-S (O
  • L 1 represents a radical from the series, where appropriate, monosubstituted to trisubstituted by C 1 -C 6 -alkyl which is unsubstituted or substituted by fluorine, chlorine, bromine, methoxy, ethoxy or cyano, optionally monosubstituted to disubstituted by fluorine, chlorine, bromine, methyl, ethyl, Difluoromethyl, trifluoromethyl, methoxy, ethoxy, Me-S (O) n -, Et-S (0) n -, difluoromethoxy, trifluoromethoxy, trifluoromethyl-S (0) n -, difluoroethyl-S (0) n -, trifluoroethyl- S (0) n -, nitro or cyano substituted phenylmethyl or C3-C6-cycloalkyl,
  • L 2 is a radical from the series hydrogen, optionally monosubstituted to trisubstituted by fluorine, chlorine, methoxy or ethoxy substituted substituted Ci-C4-alkyl, Ci-C4-alkylsulfonyl, C3-C6-cycloalkylsulfonyl, Ci-C4-alkylcarbonyl or C 1 -C 4 -alkoxycarbonyl and arylmethoxycarbonyl optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy or ethoxy,
  • L 3 is a radical selected from the group consisting of hydrogen, optionally monosubstituted to trisubstituted independently of one another by halogen, hydroxyl, methoxy, ethoxy, methoxycarbonyl, ethoxycarbonyl or cyano-substituted C 1 -C 4 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl or C 1 -C 4 C4-alkoxy, optionally mono- to disubstituted independently of one another by fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or cyano substituted C3-C6-cycloalkyl or C3-C6-cycloalkyl-Ci-C4-alkyl, optionally mono- to disubstituted independently of each other by fluorine, chlorine, bromine, methyl, ethyl, difluoromethyl, tri
  • L 2 and L 3 together form an optionally mono- to disubstituted by fluorine chlorine, bromine, methyl, ethyl, methoxy or ethoxy substituted four to six membered aliphatic ring optionally containing an N, S or O atom and n is a number 0, 1 or 2 and A, Q, V, W, Y, T and R c have the meaning according to embodiment 1 or embodiment 2 or embodiment 4 or embodiment 5. (embodiment 17)
  • X is a radical selected from halogen, C (O) L 1 , C (O) OL 1 , C (O) NL 2 L 3 , optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine and bromine and / or simply by methoxy , Ethoxy, methylsulfanyl, ethylsulfanyl, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl or cyano-substituted vinyl, allyl, methallyl, 2-butenyl, propargyl, ethynyl and 2-butynyl, optionally monosubstituted to trisubstituted independently of one another by fluorine, chlorine, bromine, methyl, Ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, methyl-S (O
  • L 1 is a radical from the series methyl, ethyl, n- or iso-propyl, 1-cyano-1-methylethyl or cyclopropyl,
  • L 2 is a radical selected from the group consisting of hydrogen, methyl, ethyl, methylsulfonyl, cyclopropylsulfonyl, methoxycarbonyl, ethoxycarbonyl, 2-methoxyethoxycarbonyl, n-, iso, sec- or t-butoxycarbonyl,
  • L 3 is a radical from the series of hydrogen, methyl, ethyl, n- or iso-propyl, n-, iso, sec- or tert.
  • L 2 and L 3 together represent (CH 2 ) 5 , (CH 2 ) 4 , (CH 2 ) 3 or (CH 2 ) 20 (CH 2 ) 2 and n is a number 0, 1 or 2 ? and A, Q, V, W, Y, T and R ° have the meaning according to Embodiment 1 or Embodiment 2 or Embodiment 3. (Embodiment 18)
  • the substituted imidazolylcarboxamides of the formula (II) can be prepared by the process according to the invention in good yields and in high purity. Due to the very good functional group tolerance of zinc reagents, zinc bases are very attractive. Regio- and chemoselective metallations of imidazolylcarboxyamides in the presence of stoichiometric amounts of selective bases are possible, even at elevated temperatures, without the decomposition of the imidazole skeleton taking place or attacking sensitive functional groups. The resulting as an intermediate zinc compound can then be trapped with various electrophiles as described for example in Organic Letters 2009 (11), p 1837ff. These newly substituted imidazopyridine derivatives can then be further reacted as valuable synthons.
  • Negishi couplings can yield good yields of target product in the context of a method according to the invention even in the presence of, for example, ort / zo substituents on the pyridine, although such couplings with 2-substituted pyridine are so far known to provide very low yields.
  • sensitive functional groups such as, for example, amides, esters or fluorine atoms
  • halogen includes those elements selected from the group consisting of fluorine, chlorine, bromine and iodine.
  • halides in the context of the present invention describes compounds between halogens and elements of other groups of the periodic table, wherein salt-like halides (ionic compounds (salts)) consisting of anions and cations due to the large difference in electronegativity between the elements involved and by electrostatic Interactions are held together) or covalent halides (covalent compounds in which the difference in electronegativity is not so great as in the abovementioned ionic compounds but the bonds have a charge polarity), depending on the nature of the chemical bond halides.
  • salt-like halides ionic compounds (salts)
  • covalent halides covalent compounds in which the difference in electronegativity is not so great as in the abovementioned ionic compounds but the bonds have a charge polarity
  • pivaloyl in connection with the present invention describes the deprotonated radical of pivalic acid (IX) with the empirical formula (CHs ⁇ CCC H.
  • O-pivaloyl means that the pivaloyl residue is attached via the deprotonated oxygen atom of the acid group.
  • Optionally substituted groups may be monosubstituted or polysubstituted, with multiple substituents the substituents may be the same or different.
  • alkyl either alone or in combination with other terms, such as, for example, haloalkyl, in the context of the present invention means a radical of a saturated, aliphatic hydrocarbon group having 1 to 12 carbon atoms
  • C 1 -C 12 -alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, iso -Pentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, 1, 2-dimethylpropyl, hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-dodecyl.
  • alkenyl either alone or in combination with other terms, according to the invention a linear or branched C2-Ci2-alkenyl radical having at least one double bond, for example vinyl, allyl, 1 Propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1,3-pentadienyl, 1-hexenyl, 2 Hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and 1, 4-hexadienyl.
  • alkynyl either alone or in combination with other terms, according to the invention a linear or branched C2-Ci2-alkynyl having at least one triple bond, for example, ethynyl, 1-propynyl and propargyl.
  • the alkynyl radical may also have at least one double bond.
  • cycloalkyl either alone or in combination with other terms, according to the invention a C3-C8-cycloalkyl understood, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, understood ,
  • alkoxy either alone or in combination with other terms, such as, for example, haloalkoxy, is understood herein to mean a radical O-alkyl, the term “alkyl” having the meaning given above.
  • Halogen-substituted radicals are halogenated once or several times up to the maximum possible number of substituents.
  • the halogen atoms may be the same or different.
  • aryl refers to an aromatic radical having 6 to 14 carbon atoms, preferably phenyl, naphthyl, anthryl or phenanthrenyl, more preferably phenyl the term “arylalkyl” a combination of inventively defined radicals "aryl” and “alkyl” understood, the radical is generally bound via the alkyl group, examples of which are benzyl, phenylethyl or a-methylbenzyl, benzyl is particularly preferred.
  • hetaryl means a mono-, bi- or tricyclic heterocyclic group of C atoms and at least one heteroatom, at least one cycle being aromatic, preferably the hetaryl group 3, 4, 5, 6, 7 or 8 C atoms and is selected from the series furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1, 2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1, 2,3-oxadiazolyl, 1, 2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5- - - -
  • optionally substituted radicals may be monosubstituted or polysubstituted, with multiple substituents the substituents being the same or different.
  • step a) The reaction of the compounds of the formula (I) to give compounds of the formula (III) in the first process step (step a)) takes place in the presence of a zinc-organometallic base of the structure (NR a R b ) -Zn-R c or (NR a R b ) 2 -Zn in which (embodiment Bl) R c is as defined above (embodiment 1) (therefore represents halogen or -O-pivaloyl),
  • R a and R b together form a - (CFh)!, - (CFh ⁇ or - (CH 2) 20 (CH 2) 2 group, each of these groups being optionally substituted by 1, 2, 3 or 4 R d radicals may be substituted and
  • R d is selected from the group consisting of methyl, ethyl, n-propyl and i-propyl.
  • R c is as defined above as preferred (embodiment 2) (therefore represents -O-pivaloyl, chlorine, bromine or iodine),
  • R a and R b together form a - (CFh ⁇ group, where each of these groups may optionally be substituted by 1, 2, 3 or 4 R d radicals, and
  • R d is selected from the group consisting of methyl and ethyl. It is particularly preferable that (Embodiment B-3)
  • R c is as defined above (embodiment 5) (hence bromine or chlorine, preferably chloro) and
  • R a and R b together form a - (CFh ⁇ group substituted by 4 methyl groups.
  • the remainder definitions listed above can be combined as desired with one another, ie also between the respective preferred ranges.
  • the structural element (NR a R b ) is tetramethylpiperidine (TMP) of the formula (V).
  • Zinc-organometallic bases which are very particularly preferred according to the invention are accordingly characterized in that zinc is bonded to TMP, in particular as zinc halide and very particularly preferably as zinc chloride.
  • the organometallic base is present in conjunction with alkali metal or alkaline earth halides.
  • bases of the formulas (VI) and (VII) Particularly preferred such alkali or Erdalkalihalogenide are lithium chloride and magnesium chloride, very particularly preferred is lithium chloride.
  • very particularly preferred organometallic bases are therefore TMP-ZnCl or LiCl (TMP) 2 Zn or 2LiCl (TMP) 2 Zn-2LiCl 2 MgCl 2 (embodiment B-6).
  • TMP is ZnCl-LiCl (VIII, design B-7).
  • Embodiment 5 Embodiment B-1
  • Embodiment 5 Embodiment B-2
  • Embodiment 5 Embodiment B-3
  • Embodiment 5 Embodiment B-4
  • Embodiment 5 Embodiment B-5
  • Embodiment 5 Embodiment B-6
  • Embodiment 5 Embodiment B-7
  • Embodiment 6 Embodiment B-1
  • Embodiment 6 Embodiment B-2
  • Embodiment 6 Embodiment B-3
  • Embodiment 6 Embodiment B-4
  • Embodiment 6 Embodiment B-5
  • Embodiment 6 Embodiment B-6
  • Embodiment 6 Embodiment B-7
  • Embodiment 7 Embodiment B-1
  • Embodiment 7 Embodiment B-2
  • Embodiment 7 Embodiment B-3
  • Embodiment 7 Embodiment B-4
  • Embodiment 7 Embodiment B-5
  • Embodiment 7 Embodiment B-6
  • Embodiment 7 Embodiment B-7
  • Embodiment 8 Embodiment B-1
  • Embodiment 8 Embodiment B-2
  • Embodiment 8 Embodiment B-3
  • Embodiment 8 Embodiment B-4
  • Embodiment 8 Embodiment B-5
  • Embodiment 8 Embodiment B-6
  • Embodiment 8 Embodiment B-7
  • Embodiment 9 Embodiment B-1
  • Embodiment 9 Embodiment B-2
  • Embodiment 9 Embodiment B-3
  • Embodiment 9 Embodiment B-4
  • Embodiment 9 Embodiment B-5
  • Embodiment 9 Embodiment B-6
  • Embodiment 9 Embodiment B-7
  • Embodiment 10 Embodiment Bl - -
  • Embodiment 10 Embodiment B-2
  • Embodiment 10 Embodiment B-3
  • Embodiment 10 Embodiment B-4
  • Embodiment 10 Embodiment B-5
  • Embodiment 10 Embodiment B-6
  • Embodiment 10 Embodiment B-7
  • Embodiment 11 Embodiment B-1
  • Embodiment 11 Embodiment B-2
  • Embodiment 11 Embodiment B-3
  • Embodiment 11 Embodiment B-5
  • Embodiment 11 Embodiment B-6
  • Embodiment 11 Embodiment B-7
  • Embodiment 12 Embodiment B-1
  • Embodiment 12 Embodiment B-2
  • Embodiment 12 Embodiment B-3
  • Embodiment 12 Embodiment B-4
  • Embodiment 12 Embodiment B-5
  • Embodiment 12 Embodiment B-6
  • Embodiment 12 Embodiment B-7
  • Embodiment 13 Embodiment B-1
  • Embodiment 13 Embodiment B-2
  • Embodiment 13 Embodiment B-3
  • Embodiment 13 Embodiment B-5
  • Embodiment 13 Embodiment B-6
  • Embodiment 14 Embodiment B-1
  • Embodiment 14 Embodiment B-2
  • Embodiment 14 Embodiment B-3
  • Embodiment 14 Embodiment B-4
  • Embodiment 14 Embodiment B-5
  • Embodiment 14 Embodiment B-6
  • Embodiment 15 Embodiment B-1
  • Embodiment 15 Embodiment B-2
  • Embodiment 15 Embodiment B-3 - 5-
  • the zinc organometallic base in the process according to the invention in a total amount of 0.5 to 5 equivalents, preferably from 0.8 to 2 equivalents, more preferably from 1 to 1.5 equivalents, and particularly preferably from 1.0 to 1, 2 equivalents, based on the compound of formula (I) used.
  • An advantage of the method according to the invention is in this respect that the organometallic base can be used in almost stoichiometric amounts.
  • reaction of the compounds of the formula (III) to give compounds of the formula (II) in the second process step (step b)) takes place in the presence of a compound XZ in which X has the meaning according to one of the embodiments 1 to 5 and Z is preferably chlorine, Bromine, iodine or fluorine (Embodiment (C-1), more preferably bromine or iodine (C-2), and most preferably iodine (C-3).
  • X has the meaning according to one of the embodiments 1 to 5 and Z is preferably chlorine, Bromine, iodine or fluorine (Embodiment (C-1), more preferably bromine or iodine (C-2), and most preferably iodine (C-3).
  • Table 2 lists compounds X-Z which may be used in a process according to the invention.
  • the compound XZ in the process according to the invention in a total amount of 0.5 to 10.0 equivalents, preferably from 0.8 to 5 equivalents, more preferably from 1 to 2.5 equivalents, and particularly preferably from 1.0 to 2, 0 equivalents, based on the compound of formula (I) used.
  • the reaction according to the invention of the compounds of the formula (I) to give compounds of the formula (III) and furthermore to compounds of the formula (II) is preferably carried out in each case in the presence of an organic solvent.
  • Suitable solvents are in principle all organic solvents which are inert under the reaction conditions used and in which the compounds to be reacted have sufficient solubility.
  • Particularly suitable solvents include: tetrahydrofuran (THF), 1,4-dioxane, diethyl ether, diglyme, methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), 2-methyl-THF, toluene, xylenes, mesitylene, ethylene carbonate . - 7-
  • Propylene carbonate N, N-dimethylacetamide, ⁇ , ⁇ -dimethylformamide (DMF), N-methylpyrrolidone (NMP), N-ethyl-2-pyrrolidone (NEP), N-butyl-2-pyrrolidone (NBP); N, N'-dimethylpropyleneurea (DMPU), halogenated hydrocarbons and aromatic hydrocarbons, in particular chlorohydrocarbons such as tetrachlorethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichlorethylene, pentachloroethane, difluorobenzene, 1, 2-dichloroethane, chlorobenzene, bromobenzene, Dichlorobenzene, especially 1,2-dichlorobenzene, chlorotoluene, trichloro
  • solvent mixtures preferably mixtures of the abovementioned solvents such as tetrahydrofuran (THF), 1,4-dioxane, diethyl ether, diglyme, methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), 2-methyl-THF, toluene, xylenes, mesitylene, dimethylformamide (DMF) can be used.
  • solvents preferably mixtures of the abovementioned solvents such as tetrahydrofuran (THF), 1,4-dioxane, diethyl ether, diglyme, methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), 2-methyl-THF, toluene, xylenes, mesitylene, dimethylformamide (DMF)
  • Preferred solvents are THF, ⁇ , ⁇ -dimethylformamide (DMF), 1,4-dioxane, diglyme, methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), 2-methyl-THF, toluene and 4-methoxybenzene.
  • Particularly preferred solvents are THF and ⁇ , ⁇ -dimethylformamide (DMF), most preferably THF.
  • the solvent may further be degassed (oxygen-free).
  • the same solvent is used for both process steps a) and b).
  • the solvents then likewise preferably being selected from the abovementioned solvents and the particulars indicated as being preferred, particularly preferred and very particularly preferred Solvent to the respective process step a) or b) are to be obtained.
  • the reaction in process step a) is generally carried out at a temperature between 0 ° C and 80 ° C and more preferably between 10 ° C and 70 ° C, between 15 ° C and 60 ° C, between 20 ° C and 50 ° C, between 20 ° C and 40 ° C and most preferably between 20 ° C and 35 ° C, for example at room temperature or 25 ° C, performed.
  • the reaction in process step a) generally takes place in a period of from 10 to 90 minutes, preferably from 15 to 60 minutes and more preferably from 20 to 45 minutes, for example 30 minutes.
  • the compounds of the formula (III) are versatile intermediates to which in process step b) a plurality of substituents X can be introduced directly by reaction with compounds of the formula XZ via various reactions.
  • the reaction of the compounds of the formula (III) to give compounds of the formula (II) (step b), ie the introduction of the radical X, is preferably carried out by coupling, particularly preferably by cross-coupling, or by nucleophilic substitution.
  • the reaction in process step b) is generally carried out at a temperature between -40 ° C and 120 ° C and more preferably between -35 ° C and 100 ° C and most preferably between -30 ° C and 90 ° C.
  • the reaction in process step b) generally takes place in a period of from 5 minutes to 12 hours, preferably from 10 minutes to 10 hours and particularly preferably from 20 minutes to 2 hours.
  • the reaction is usually carried out at normal pressure, but can also be carried out at elevated or reduced pressure.
  • the isolation of the desired compounds of the formula (II) can be carried out, for example, by aqueous workup in the presence of saturated ammonium chloride or sodium thiosulfate solutions and / or subsequent chromatography. Such methods are known to those skilled in the art and also include crystallization from an organic solvent or solvent mixture.
  • the compounds of the formula (II) can be prepared by cross-coupling, in particular by Negishi cross-coupling of the compounds of the formula (III) with the compounds XZ in the presence of a catalyst, as described for example in Angewandte Chemie International Edition 2013 (53), p 143 ff ,
  • X-Z compounds are preferably used in which X has the meaning according to one of embodiments 1 to 5, but does not stand for halogen and Z has the abovementioned meanings, in particular according to one of the embodiments C-1 to C-3.
  • the compound XZ is preferably used in a total amount of from 0.5 to 10.0 equivalents, preferably from 0.8 to 5 equivalents, more preferably from 1 to 2.5 equivalents, and particularly preferably from 1.0 to 2.0 equivalents, based on the compound of formula (I) used.
  • the cross-coupling also takes place in the presence of a catalyst.
  • the catalyst is a palladium compound or a nickel compound.
  • the catalyst is a Palladium compound.
  • very particular preference is given to tetrakis (triphenylphosphine) palladium (0), abbreviated Pd (PPli3) 4.
  • catalyst in particular tetrakis (triphenylphosphine) palladium (0), are used.
  • the cross-coupling is generally carried out at a temperature between 0 ° C and 120 ° C, and more preferably between 10 ° C and 100 ° C, and most preferably between 25 ° C and 90 ° C.
  • the cross-coupling is generally carried out in a period of from 5 minutes to 12 hours, preferably from 15 minutes to 10 hours and more preferably from 30 minutes to 2 hours.
  • the compounds of formula (II) can be prepared Copper-catalyzed reactions of the compounds of formula (III) with the compounds X-Z, as described for example in Organic Letters 2008 (10), p 2497ff.
  • compound X-Z is an interhalogen compound, preferably elemental halogen.
  • X and Z do not necessarily stand for the same halogen.
  • X can be iodine or bromine and Z is chlorine, bromine or iodine.
  • the compound X-Z is an elemental halogen, in particular F 2, Cb, Br 2 or I 2. Particular preference is given to I 2 or Br 2, very particular preference being given to I 2.
  • the compound XZ is preferably used in a total amount of from 0.5 to 10.0 equivalents, preferably from 0.8 to 5 equivalents, more preferably from 1 to 2.5 equivalents, and particularly preferably from 1.0 to 2.0 equivalents, based on the compound of formula (I) used.
  • the reaction is generally carried out at a temperature between -10 ° C and 70 ° C, and more preferably between -5 ° C and 50 ° C, and most preferably between 10 ° C and 25 ° C.
  • the reaction generally takes place in a period of from 5 to 60 minutes, preferably from 15 to 45 minutes and more preferably from 20 to 40 minutes.
  • the preparation of the compounds of the formula (I) is described, for example, in WO2016 / 128298 (page 24, method D).
  • a further subject of the present invention are compounds of the formula (IIIa) or (IIIb)
  • the compounds of the formula (IIIa) or (IIIb) can also be complexed with salts, the salts preferably being alkali metal or alkaline earth halides, preferably lithium chloride and / or magnesium chloride and more preferably lithium chloride.
  • the compounds of the formula (IIIa) and (IIIb) are versatile and thus very valuable synthons for, for example, the preparation of the compounds of the formula (II).
  • the determination with the LC-MS in the acidic range is carried out at pH 2.7 with 0.1% aqueous formic acid and acetonitrile (contains 0.1% formic acid) as eluent; linear gradient from 10%> acetonitrile to 95%> acetonitrile.
  • the determination with the LC-MS in the neutral range is carried out at pH 7.8 with 0.001 molar aqueous ammonium bicarbonate solution and acetonitrile as eluent; linear gradient from 10%> acetonitrile to 95%> acetonitrile.
  • the calibration is carried out with unbranched alkan-2-ones (with 3 to 16 carbon atoms) whose logP values are known (determination of the logP values by means of the retention times by linear interpolation between two consecutive alkanones).
  • the NMR data of selected examples are given in classical form ( ⁇ values, multiplet splitting, number of H atoms) a.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne un procédé pour produire des imidazolylcarboxyamides substitués de formule (II) à partir de composés de formule (I) via une étape intermédiaire de formule (IIIa) ou (IIIb) dans lesquels les éléments structuraux indiqués dans les formules (I), (II), (IIIa) et (IIIb) ont les significations mentionnées. L'invention concerne en outre les composés de formules (IIIa) et (IIIb).
EP18725437.0A 2017-05-15 2018-05-08 Procédé pour produire des imidazolylcarboxyamides substitués Withdrawn EP3625219A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP17171039 2017-05-15
PCT/EP2018/061827 WO2018210625A1 (fr) 2017-05-15 2018-05-08 Procédé pour produire des imidazolylcarboxyamides substitués

Publications (1)

Publication Number Publication Date
EP3625219A1 true EP3625219A1 (fr) 2020-03-25

Family

ID=58709355

Family Applications (1)

Application Number Title Priority Date Filing Date
EP18725437.0A Withdrawn EP3625219A1 (fr) 2017-05-15 2018-05-08 Procédé pour produire des imidazolylcarboxyamides substitués

Country Status (9)

Country Link
US (1) US10961220B2 (fr)
EP (1) EP3625219A1 (fr)
JP (1) JP2020519657A (fr)
KR (1) KR20200005647A (fr)
CN (1) CN110637014A (fr)
BR (1) BR112019023991A2 (fr)
MX (1) MX2019013759A (fr)
TW (1) TW201906833A (fr)
WO (1) WO2018210625A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3135706A1 (fr) 2019-05-03 2020-11-12 Wen Xu Stabilisation de concentres en suspension au moyen de lignosulfonate hautement sulfone
EP3962269A1 (fr) 2019-05-03 2022-03-09 Basf Se Stabilisation de concentrés de suspension par ricinoléine éthoxylée
WO2020224943A1 (fr) 2019-05-03 2020-11-12 Basf Se Stabilisation de concentrés en suspension au moyen de la silice sublimée hydrophobe

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2456308A2 (fr) 2009-07-24 2012-05-30 Basf Se Composés dérivés de pyridine pour le côntrole des animaux nuisibles invertébrés
TWI702212B (zh) 2015-02-09 2020-08-21 德商拜耳作物科學股份有限公司 作為除害劑之經取代的２－硫基咪唑基羧醯胺類

Also Published As

Publication number Publication date
US20200172511A1 (en) 2020-06-04
WO2018210625A1 (fr) 2018-11-22
KR20200005647A (ko) 2020-01-15
CN110637014A (zh) 2019-12-31
TW201906833A (zh) 2019-02-16
BR112019023991A2 (pt) 2020-06-16
US10961220B2 (en) 2021-03-30
JP2020519657A (ja) 2020-07-02
MX2019013759A (es) 2020-01-30

Similar Documents

Publication Publication Date Title
EP3625219A1 (fr) Procédé pour produire des imidazolylcarboxyamides substitués
JP7283861B2 (ja) 安定結晶形のカルボキサミド誘導体およびそのジアステレオマー
WO2011157664A1 (fr) Procédé de production de dérivés de diamide d'acide anthranilique substitués par tétrazole et nouvelle modification cristalline de ces dérivés
EP3500568B1 (fr) Procédé pour la préparation de dérivés de la 2-(3,6-dihalopyridin-2-yl)-3h-imidazol[4,5-c]pyridine et composés similaires par reaction d'un dérivé de la 3h-imidazol[4,5-c]pyridine avec une base metal-organic d'une amine de zinc
KR101855334B1 (ko) 옥사졸리디논 유도체의 중간체 제조방법
EP3512847B1 (fr) Procédé pour la preparation des bicycles halogénés
EP3577114B1 (fr) Procédé de fabrication de dérivés d'imidazopyridine halogénée
EP3864016B1 (fr) Procédé de préparation de dérivés d'imidazole substitués
WO2012084854A1 (fr) Procédé de préparation d'oxindoles n-sulfonyle substitués
EP3864015B1 (fr) Procédé de préparation de dérivés d'imidazoles
CN110452174A (zh) 制备1-芳基-5-烷基吡唑化合物的改善的方法
CN113121438A (zh) 一种异喹啉酮类化合物的制备方法
EP3481805B1 (fr) Procede de fabrication de derives de pyridine halogenee
EP3636645A1 (fr) Procédé de production de préparation de dérivés de pyridine substitués par du soufre
EP0168607B1 (fr) Acides pyrrolidinecarboxyliques, procédé pour leur fabrication
Kakehi et al. Facile synthesis of 1-alkyl-2-and 4-allylidenkdihydropyridine derivatives
DE10336497A1 (de) Substituierte Pyridine
DD147774A3 (de) Verfahren zur herstellung von 2'-halogen-2'-desoxy-5-fluoruridinen und ihren 3',5'-di-o-benzoylderivaten
CH651036A5 (de) 1-benzyl-4-(4-(2-pyrimidinylamino)-benzyl)-2,3-dioxopiperazin-derivate, salze derselben, verfahren zur herstellung derselben und carcinostatische mittel mit einem gehalt derselben.
WO2002094817A1 (fr) Procédé de purification de triazolylméthyle-oxirannes

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20191216

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20201207

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20210820

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20220104