Method for producing substituted anthranilic acid derivatives

Patent metadata

Field	Value
Publication number	US-9670182-B2
Application number	US-201514924889-A
Country	US
Kind code	B2
Filing date	Oct 28, 2015
Priority date	Feb 7, 2012
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

The present invention relates to a process for preparing substituted anthranilic acid derivatives of the formula (I)

in which R 1 , R 2 , R 3 and R 4 are each as defined in the description, by conversion of compounds of the general formula (IV) in the presence of a palladium catalyst and carbon monoxide. The present invention likewise relates to compounds of the general formula (IV).

First claim

The invention claimed is:

1. Process for preparing a compound of formula (I)

in which
R 1 is a hetaryl radical of formula (II)

where
R 8 is C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, which may optionally be mono- or polysubstituted, identically or differently by fluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl,
Z is CH or N,
and
Y is hydrogen, fluorine, chlorine, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of formula (III)

where
R 9 is C 1 -C 5 -alkyl which may optionally be mono- or polysubstituted identically or differently by halogen,
R 2 is an OR 5 or NR 6 R 7 radical,
where
R 5 , R 6 and R 7 are each independently hydrogen, C 1 -C 6 -alkyl, or C 6 -C 10 -aryl,
R 3 is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl,
R 4 is hydrogen, fluorine, chlorine, cyano, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino, (C 1 -C 4 -alkoxy)imino, (C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy)imino, SF 5 or C 3 -C 6 -trialkylsilyl,
comprising reacting a substituted anthranilamide derivative of the formula (IV)

in which the R 1 , R 3 and R 4 radicals are each as defined above
and X is chlorine, bromine or iodine,

in the presence of a palladium catalyst and optionally of a phosphine ligand simultaneously with carbon monoxide and a compound of formula (V)
R 5 —OH  (V)

in which R 5 is as defined above
or a compound of formula (VI)
HNR 6 R 7   (VI)

in which R 6 and R 7 are each as defined above,
wherein the compound of formula (IV) is prepared by reacting a compound of formula (IX)

in which X, R 3 and R 4 are each as defined above
with an acid of formula (VIII)
R 1 COOH  (VIII)

in which R 1 is as defined above.

2. Process according to claim 1 , wherein the compound of formula (IV) is prepared in the presence of a condensing agent and of a base.

3. Process according to claim 1 , wherein the palladium catalyst used is a palladium(II) salt and/or Pd(0) species.

4. Process according to claim 3 , wherein the palladium catalyst used is bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium bromide and/or palladium acetate.

5. Process according to claim 1 , wherein the phosphine ligand is used and is a compound of formula (X)
PR 10 R 11 R 12   (X)

where the R 10 , R 11 and R 12 radicals are each independently hydrogen, linear or branched C 1 -C 8 -alkyl, vinyl, aryl or heteroaryl selected from pyridine, pyrimidine, pyrrole, thiophene and furan, which may in turn be substituted by further substituents from the group of linear or branched C 1 -C 8 -alkyl or C 6 -C 10 -aryl, linear or branched C 1 -C 8 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear or branched C 1 -C 8 -alkyl or halogenated C 6 -C 10 -aryl, C 6 -C 10 -aryloxycarbonyl, linear or branched C 1 -C 8 -alkylamino, linear or branched C 1 -C 8 -dialkylamino, C 1 -C 8 -arylamino, C 1 -C 8 -diarylamino, hydroxyl, carboxyl, cyano and halogen,
or a chelating biphosphine.

6. Process according to claim 5 , wherein the chelating biphosphine is used and is one or more selected from 1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)butane, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 1,1′-bis(diphenylphosphino)ferrocene.

7. Process according to claim 5 , wherein the phosphine ligand used is triphenylphosphine.

8. Process according to claim 5 , wherein 1-20 molar equivalents of phosphine are used, based on the amount of palladium catalyst used.

9. Process according to claim 1 , wherein R 2 is an OR 5 radical.

10. Process according to claim 1 , wherein R 2 is an NR 6 R 7 radical.

11. Process according to claim 1 , wherein R 3 is singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl.

12. Process according to claim 1 , wherein R 4 is fluorine, chlorine, cyano, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino, (C 1 -C 4 -alkoxy)imino, (C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy)imino, SF 5 or C 3 -C 6 -trialkylsilyl.

13. Process according to claim 1 , wherein a phosphine ligand is used.

14. Process according to claim 1 , wherein a compound of formula (V) is used.

15. Process according to claim 1 , wherein a compound of formula (VI) is used.

Assignees

• Bayer Ip Gmbh

Inventors

• Himmler Thomas
• Pazenok Sergii
• Volz Frank
• Lui Norbert

Classifications

• C07C253/30

  by reactions not involving the formation of cyano groups · CPC title

• C07C255/60

  at least one of the singly-bound nitrogen atoms being acylated · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title