Preparation of substituted 3-aryl-5-trifluoromethyl-1,2,4-oxadiazoles

Patent metadata

Field	Value
Publication number	US-11021452-B2
Application number	US-201816634202-A
Country	US
Kind code	B2
Filing date	Jul 21, 2018
Priority date	Jul 28, 2017
Publication date	Jun 1, 2021
Grant date	Jun 1, 2021

Abstract

The present invention relates to a process for the preparation of substituted 3-aryl-5-trifluoromethyl-1,2,4-oxadiazoles (compounds I), which can be obtained through reaction of hydroxyamidine compounds of formula II with trifluoroacetyl halides IIa.

First claim

The invention claimed is:

1. A process for preparing compounds of formula I,

wherein
A 1 is N or CH;
A 2 is N or CH;
R A is hydrogen or halogen;
R is methyl, trichloromethyl, ethyl, iso-propyl, OH, SH, cyano, halogen, CH 2 F, CHF 2 , 2,2,2-trifluoroethyl, cyclopropyl, —COOH, —COOR 1 , —C(═W)NR 1 R 2 , —CR 3 R 4 NR 1 R 2 , —CR 3 R 4 OR 1 , —CR 3 (═NR 1 ), —CR 3 (═O), —CR 3 R 4 COOH, —CR 3 R 4 COR 1 —CR 3 R 4 C(═W)NR 1 R 2 , —OCR 3 R 4 COOH, —OCR 3 R 4 COR 1 , —OCR 3 R 4 C(═W)NR 1 R 2 , —CR 3 R 4 NR 2 C(═W)R 1 , —CR 3 R 4 S(═O) 2 R 1 , or —CR 3 R 4 NR 2 S(═O) 2 R 1 ;
W is O or S;
R 2 is selected from the group consisting of hydrogen, formyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, C 3 -C 11 -cycloalkyl, C 3 -C 6 -cycloalkenyl, C 3 -C 11 -cycloalkyl-C 1 -C 4 -alkyl, phenyl-C 1 -C 4 -alkyl, phenyl, pyridinyl, —C(═O)—(C 1 -C 6 -alkyl), —C(═O)—(C 3 -C 11 -cycloalkyl), —C(═O)—(C 1 -C 6 -alkoxy) and —N(R 2a ) 2 ;
R 2a is independently selected from the group consisting of hydrogen, OH, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 11 -cycloalkyl, C 3 -C 8 -cycloalkenyl, C 1 -C 6 -alkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl and C 1 -C 6 -alkylthio;
and wherein any of the aliphatic or cyclic groups in R 2 are unsubstituted or substituted with 1, 2, 3 or up to the maximum possible number of identical or different radicals selected from the group consisting of halogen, hydroxy, oxo, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy and C 3 -C 11 -cycloalkyl;
R 1 is C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 3 -C 11 -cycloalkyl, C 3 -C 8 -cycloalkenyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxyimino-C 1 -C 4 -alkyl, C 2 -C 6 -alkenyloxyimino-C 1 -C 4 -alkyl, C 2 -C 6 -alkynyloxyimino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylamino, diC 1 -C 6 -alkylamino, —C(═O)—(C 1 -C 6 -alkyl), —C(═O)—(C 1 -C 6 -alkoxy), phenyl-C 1 -C 4 -alkyl, phenyl-C 1 -C 4 -alkenyl, phenyl-C 1 -C 4 -alkynyl, heteroaryl-C 1 -C 4 -alkyl, phenyl, naphthyl or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocycle, wherein the ring member atoms of said mono- or bicyclic heterocycle include besides carbon atoms further 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S; and wherein the heteroaryl group in the group heteroaryl-C 1 -C 4 -alkyl is a 5- or 6-membered aromatic heterocycle, wherein the ring member atoms of the heterocyclic ring include besides carbon atoms 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from the group consisting of 0 and S; and wherein any of the above-mentioned aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3 or up to the maximum possible number of identical or different groups R 1a ; or
R 1 and R 2 , together with the nitrogen atom to which R 2 is attached, and together with interjacent group —C(═W)—, if present, which is located between said nitrogen atom and the group R 1 , form a saturated or partially unsaturated mono- or bicyclic 3- to 10-membered heterocycle, wherein the heterocycle includes beside one nitrogen atom and one or more carbon atoms no further heteroatoms or 1, 2 or 3 further heteroatoms independently selected from the group consisting of N, O and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from the group consisting of 0 and S; and wherein the heterocycle is unsubstituted or substituted with 1, 2, 3, 4 or up to the maximum possible number of identical or different groups R 1a ; or
if R 2 is —N(R 2a ) 2 , R 1 and one of the two groups R 2a , together with the nitrogen atom to which R 2a is attached, and together with interjacent groups, which are located between said nitrogen atom and the group R 1 , form a saturated or partially unsaturated mono- or bicyclic 3- to 10-membered heterocycle, wherein the heterocycle includes beside two nitrogen atoms and one or more carbon atoms no further heteroatoms or 1, 2 or 3 further heteroatoms independently selected from the group consisting of N, O and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from the group consisting of O and S; and wherein the heterocycle is unsubstituted or substituted with 1, 2, 3, 4 or up to the maximum possible number of identical or different groups R 1a ;
R 1 a is halogen, oxo, cyano, NO 2 , OH, SH, NH 2 , C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 8 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 3 -C 8 -cycloalkyl, —NHSO 2 -C 1 -C 4 -alkyl, (C═O)—C 1 -C 4 -alkyl, C(═O)—C 1 -C 4 -alkoxy, C 1 -C 6 -alkylsulfonyl, hydroxyC 1 l-C 4 -alkyl, C(═O)—NH 2 , C(═O)—NH(C 1 -C 4 -alkyl), C 1 -C 4 -alkylthio-C 1 -C 4 -alkyl, C 1 -C 4 -alkylamino-C 1 -C 4 -alkyl, diC 1 -C 4 -alkylamino-C 1 -C 4 -alkyl, aminocarbonyl-C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;
R 3 , R 4 independently of each other are selected from the group consisting of hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkenyl, C 1 -C 4 -alkynyl, C 1 -C 4 -haloalkyl and C 1 -C 4 -alkoxy; or
R 3 and R 4 together with the carbon atom to which they are bound form a cyclopropyl group;
the process comprising reacting a compound of formula II,

wherein the variables A 1 , A 2 , R and R A are as defined above for compounds of formula I, with a trifloroacetyl halide of formula IIa,

wherein Hal is chlorine or fluorine; and whereas the process is characterized in that the compounds of formula II and IIa are used in substance.

2. The process of claim 1 , wherein Hal in compound IIa is chlorine.

3. The process of claim 1 , wherein R in compounds I and II is methyl, trichloromethyl, COOH, OH, SH, cyano or halogen.

4. The process of claim 1 , wherein A 1 and A 2 are CH and R A is hydrogen or fluorine in compounds I and II.

5. The process of claim 1 , wherein the process is conducted at a temperature between −40° C. and 100° C.

6. The process of claim 1 , wherein the process is conducted at a temperature between 0° C. and 100° C.

7. The process of claim 1 , wherein the process is conducted at a pressure between 100 and 1000 kPa.

8. The process of claim 1 , wherein R in compounds I and II is methyl, and further comprising the step of reacting the compound of formula I to obtain a compound of formula Ib

9. The process of claim 8 , further comprising the step of reacting the compound of formula Ib to obtain a compound of formula III

10. The process of claim 9 , wherein the step of reacting the compound of formula Ib to obtain a compound of formula III is carried out in the presence of iron(III) chloride and water.

11. The process of claim 9 , further comprising the step of reacting the compound of formula III with a compound of formula IV
R 1 —NH—R 2   IV,

wherein R 1 and R 2 in the comp

Assignees

• Basf Se

Inventors

• Koradin Christopher
• Grammenos Wassilios
• Rack Michael
• Borate Kailaskumar
• Goetz Roland

Classifications

• C07D271/06 Primary

  1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles · CPC title

• A01N43/82

  five-membered rings with three ring hetero atoms · CPC title