Process for preparing halogenated pyridine derivatives

Patent metadata

Field	Value
Publication number	US-2019202829-A1
Application number	US-201716325666-A
Country	US
Kind code	A1
Filing date	Aug 9, 2017
Priority date	Aug 16, 2016
Publication date	Jul 4, 2019
Grant date	—

Abstract

The present invention relates to a process for preparing halogenated pyridine derivatives of the formula (II) proceeding from compounds of the structure Q-H via intermediates of the formula (IIIa) or (IIIb)

in which
Q is a structural element

where the symbol # indicates the bond to the rest of the molecule and A, Q 1 , Q 2 , Q 3 , Q 4 , Q 5 and Q 6 have the definitions given in the description,
W is halogen,
Y is halogen, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl, and
R 2 is halogen or —O-pivaloyl.

First claim

1 . Process for preparing compound of formula (II)

in which
Q is a structural element

where the symbol # indicates the bond to the rest of the molecule and
Q 1 is N or CR 6 ,
Q 2 is N or CR 6 ,
Q 3 is N or C,
Q 4 is O, S, N or NR 7 ,
Q 5 is N or C,
Q 6 is N or CH,
R 6 is hydrogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )cyanoalkyl, (C 1 -C 4 )hydroxyalkyl, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkoxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyl, (C 2 -C 4 )cyanoalkenyl, (C 2 -C 4 )alkynyl, (C 2 -C 4 )alkynyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkyl-(C 3 -C 6 )cycloalkyl, halo(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkylthio-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphinyl-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphonyl-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )alkyl,
R 7 is (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )cyanoalkyl, (C 1 -C 4 )hydroxyalkyl, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkoxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkenyl, (C 2 -C 4 )cyanoalkenyl, (C 2 -C 4 )alkynyl, (C 2 -C 4 )alkynyloxy-(C 1 -C 4 )alkyl, (C 2 -C 4 )haloalkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkyl-(C 3 -C 6 )cycloalkyl, halo(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkylthio-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphinyl-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphonyl-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )alkyl, and
A is hydrogen, cyano, halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )haloalkenyl, (C 2 -C 4 )alkynyl, (C 2 -C 4 )haloalkynyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkyl-(C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )alkoxyimino, (C 1 -C 4 )alkylthio, (C 1 -C 4 )haloalkylthio, (C 1 -C 4 )alkylsulphinyl, (C 1 -C 4 )haloalkylsulphinyl, (C 1 -C 4 )alkylsulphonyl, (C 1 -C 4 )haloalkylsulphonyl, (C 1 -C 4 )alkylsulphonyloxy, (C 1 -C 4 )alkylcarbonyl, (C 1 -C 4 )haloalkylcarbonyl, aminocarbonyl, (C 1 -C 4 )alkylaminocarbonyl, di-(C 1 -C 4 )alkylaminocarbonyl, (C 1 -C 4 )alkylsulphonylamino, (C 1 -C 4 )alkylamino, di-(C 1 -C 4 )alkylamino, aminosulphonyl, (C 1 -C 4 )alkylaminosulphonyl or di-(C 1 -C 4 )alkylaminosulphonyl,
or A is —O—CF 2 —O— and, together with Q 1 and the carbon atom to which it is bonded, forms a five-membered ring where Q 1 is carbon,
W is halogen, and
Y is halogen, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl,
wherein, first a), a compound Q-H in which Q is as defined above
is reacted with an organozinc base of the structure (NR 3 R 4 )—Zn—R 2 or (NR 3 R 4 ) 2 —Zn in which
R 2 is halogen or —O-pivaloyl and
R 3 and R 4 together form a —(CH 2 ) 4 —, —(CH 2 ) 5 — or —(CH 2 ) 2 O(CH 2 ) 2 — group, where each of these groups may optionally be substituted by 1, 2, 3 or 4 R 5 radicals and R 5 is selected from the group consisting of methyl, ethyl, n-propyl and i-propyl,
to give a compound of formula (IIIa) or formula (IIIb)

in which Q and R 2 each have the definitions given above,
and said compound of formula (IIIa) or (IIIb) is reacted in b) with a compound of formula (I)

in which X is halogen and W and Y each have the definitions given above, in the presence of a catalyst, to give the compound of formula (II).

2 . Process according to claim 1 , wherein
Q is a structural element from the group of Q1 to Q15

R 7 is (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylthio-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphinyl-(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylsulphonyl-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkylcarbonyl-(C 1 -C 4 )alkyl,
A is fluorine, chlorine, bromine, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl (CH 2 CFH 2 , CHFCH 3 ), difluoroethyl (CF 2 CH 3 , CH 2 CHF 2 , CHFCFH 2 ), trifluoroethyl, (CH 2 CF 3 , CHFCHF 2 , CF 2 CFH 2 ), tetrafluoroethyl (CHFCF 3 , CF 2 CHF 2 ), pentafluoroethyl, trifluoromethoxy, difluorochloromethoxy, dichlorofluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl,
W is fluorine, chlorine or bromine,
R 2 is halogen, especially chlorine, bromine or iodine,
X is halogen, especially bromine or iodine, and
Y is fluorine, chlorine, bromine, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 4 )-alkyl.

3 . Process according to claim 1 , wherein
Q is a structural element from the group of Q2, Q3, Q10, Q12, Q14 and Q15 R 7 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, A is trifluoromethyl, fluoroethyl (CH 2 CFH 2 , CHFCH 3 ), difluoroethyl (CF 2 CH 3 , CH 2 CHF 2 , CHFCFH 2 ), trifluoroethyl, (CH 2 CF 3 , CHFCHF 2 , CF 2 CFH 2 ), tetrafluoroethyl (CHFCF 3 , CF 2 CHF 2 ), pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl, W is fluorine or chlorine, especially fluorine, R 2 is chlorine, X is bromine or iodine, especially iodine, and Y is chlorine, bromine, CO 2 R 1 or NO 2 , where R 1 is (C 1 -C 4 )-alkyl.

4 . Process according to claim 1 , wherein
Q is the structural element Q3 or Q14 R 7 is methyl, ethyl, n-propyl or isopropyl, especially methyl, A is trifluoromethyl, W is fluorine, R 2 is chlorine, X is iodine, and Y is chlorine, bromine, CO 2 R 1 or NO 2 , where R 1 is methyl.

5 . Process according to claim 1 , wherein
R 3 and R 4 together form a —(CH 2 ) 5 — group substituted by 4 methyl groups.

6 . Process according to claim 1 , wherein the organozinc base is a compound of formula (V)
(TMP) x ZnCl 2−x   (V)
in which x is the number 1 or 2.

7 . Process according to claim 1 , wherein that the organozinc base is present in conjunction with an alkali metal halide or alkaline earth metal halide, optionally lithium chloride or magnesium chloride.

8 . Process according to claim 1 , wherein the organozinc base is used in a total amount of 0.5 to 5 equivalents, based on the compound Q-H.

9 . Process according to claim 1 , wherein the compound of formula (I) is used in a total amount of 0.5 to 10.0 equivalents, based on the compound Q-H.

10 . Process according to claim 1 , wherein the catalyst is a palladium compound.

11 . Process according to claim 1 , wherein the catalyst is tetrakis(triphenylphosphine)palladium(0).

12 . Process according to claim 1 , that is conducted in the presence of a solvent selected from the group consisting of tetrahydrofuran (THF), 1,4-dioxane, diethyl ether, diglyme, methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME)

Assignees

• Bayer Cropscience Ag

Inventors

• Mosrin Marc
• Fischer Ruediger
• Hager Dominik
• Hoffmeister Laura
• Kausch-Busies Nina
• Wilcke David
• Willot Matthieu

Classifications

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• B01J2531/824

  Palladium · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D491/056

  with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring · CPC title