Method for the production of 3,5-bis(fluoroalkyl)pyrazole derivatives

Patent metadata

Field	Value
Publication number	US-9765033-B2
Application number	US-201414892280-A
Country	US
Kind code	B2
Filing date	May 19, 2014
Priority date	May 22, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

The present invention describes a novel method for preparing 3,5-bis(fluoroalkyl)pyrazole derivatives.

First claim

The invention claimed is:

1. Method for preparing a 3,5-bis(fluoroalkyl)pyrazole derivative of formula (Ia) and/or (Ib),

in which
R 1 and R 3 are each independently selected from C 1 -C 6 -haloalkyl;
R 2 is selected from H, F, Cl, Br, COOH, (C═O)OR 4 , CN and (C═O)NR 4 R 5 ;
R 4 and R 5 are each independently selected from C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl or
R 4 and R 5 may form a five- or six-membered ring together with the nitrogen atom to which they are attached;
comprising reacting in (A) one or more fluoroalkyl esters, thioesters or amides of formula (II),

in which
Z is selected from O, S, N—R 4 ;
R 4 is as defined above;
R 6 is selected from C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl or
R 4 and R 6 may form a five- or six-membered ring together with the nitrogen atom to which they are attached;
R 1 is as defined above;
with one or more compounds of formula (III),

in which the residues R 2 , R 3 , R 4 and R 5 are as defined above,
and R 7 and R 8 are each independently selected from H, C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl,
or R 7 and R 8 may form a four-, five- or six-membered ring;
in the presence of a base to give one or more compounds of formula (IV)

and which are then cyclized in (B) in the presence of an acid to give one or more compounds of formula (Ia) and (M).

2. Method according to claim 1 , wherein
R 1 and R 3 are each independently selected from difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 1,1,1-trifluoroprop-2-yl;
R 2 is selected from H, Cl, COOH, COOCH 3 , COOC 2 H 5 , COOC 3 H 7 , CN and CON(CH 3 ) 2 , CONC 3 H 7 ;
Z is selected from O, S, N—R 4 ;
R 4 is selected from methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, C 7-19 -alkylaryl, tolyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethylphenyl;
R 6 is selected from methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, C 7-19 -alkylaryl, tolyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethylphenyl or
R 4 and R 6 form a piperidine or morpholine ring together with the nitrogen atom to which they are attached;
R 7 and R 8 are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, C 7-19 -alkylaryl, tolyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethylphenyl or
R 7 and R 8 form a five- or six-membered ring.

3. Method according to claim 1 , wherein
R 1 and R 3 are each independently selected from trifluoromethyl, difluoromethyl, difluorochloromethyl, pentafluoroethyl;
R 2 is selected from H, F, Cl, Br, COOH, COOCH 3 , CN;
Z is selected from O, S, N—R 4 ;
R 4 is selected from methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, cyclopropyl, phenyl, benzyl, tolyl;
R 6 is selected from methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, cyclopropyl, phenyl, benzyl, tolyl or
R 4 and R 6 form a piperidine or morpholine ring together with the nitrogen atom to which they are attached;
R 7 and R 8 are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, cyclopropyl, phenyl, benzyl, tolyl or R 7 and R 8 form a five- or six-membered ring.

4. Method according to claim 1 , wherein
R 1 and R 3 are each independently selected from CF 2 H and CF 3 ,
R 2 is H,
Z is O,
R 6 is selected from methyl or ethyl,
R 7 and R 8 are each independently selected from H, methyl, phenyl.

5. Method according to claim 1 , wherein
R 1 and R 3 are each independently selected from CF 2 H and CF 3 ,
R 2 is H,
Z is O,
R 6 is selected from methyl or ethyl,
R 7 and R 8 are phenyl.

6. Compound of formula (IV),

in which
R 1 and R 3 are each independently selected from C 1 -C 6 -haloalkyl;
R 2 is selected from H, F, Cl, Br, COOH, (C═O)OR 4 , CN and (C═O)NR 4 R 5 ;
R 4 and R 5 are each independently selected from C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl or
R 4 and R 5 form a five- or six-membered ring together with the nitrogen atom to which they are attached;
R 7 and R 8 are each independently selected from H, C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl or
R 7 and R 8 form a five- or six-membered ring.

7. Compound of formula (IV) according to claim 6 , in which
R 1 and R 3 are each independently selected from difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 1,1,1-trifluoroprop-2-yl;
R 2 is selected from H, Cl, COOH, COOCH 3 , COOC 2 H 5 , COOC 3 H 7 , CN and CONCHS, CON(C 2 H 5 ) 2 ;
R 7 and R 8 are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-, sec- and t-butyl, isobutyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, C 7-19 -alkylaryl, tolyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethylphenyl or
R 7 and R 8 form a five- or six-membered ring.

8. Compound of formula (IV) according to claim 6 , in which
R 1 and R 3 are each independently selected from trifluoromethyl, difluoromethyl, difluorochloromethyl, pentafluoroethyl;
R 2 is selected from H, F, Cl, Br, COOH, COOCH 3 , CN;
R 7 and R 8 are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n, sec- and t-butyl, isobutyl, cyclopropyl, phenyl, benzyl, tolyl or wherein R 7 and R 8 may form a five- or six-membered ring.

9. Compound of formula (IV) according to claim 6 , in which
R 1 and R 3 are each independently selected from CF 2 H and CF 3 ,
R 2 is H,
R 7 and R 8 are each independently selected from H, methyl, phenyl.

10. Compound of formula (III),

in which
R 3 is selected from C 1 -C 6 -haloalkyl;
R 2 is selected from H, F, Cl, Br, COOH, (C═O)OR 4 , CN and (C═O)NR 4 R 5 ;
R 4 and R 5 are each independently selected from C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl or
R 4 and R 5 form a five- or six-membered ring together with the nitrogen atom to which they are attached;

Assignees

• Bayer Cropscience Ag

Inventors

• Pazenok Sergii
• Lui Norbert

Classifications

• C07D231/14

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07C251/80

  the carbon skeleton containing rings · CPC title

• C07D231/12 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07C251/88

  having also the other nitrogen atom doubly-bound to a carbon atom, e.g. azines · CPC title

• A61P31/10

  Antimycotics · CPC title