# US 7,745,634 B2 · Process for preparing triazolones

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- Number: US 7,745,634 B2
- Document ID: US7745634B2
- Status: Granted
- Kind: B2
- Application number: 12/156,145
- Filed: 2008-05-30
- Published: 2009-01-08
- Granted: 2010-06-29
- Earliest claimed: 2007-05-30
- Assignees: Roche Palo Alto LLC
- Inventors: Humberto Bartolome Arzeno; Gary M. Lee; Michael Martin; Keshab Sarma; Jiang Zhu
- Web page: https://patentgrep.com/patent/US7745634B2

## CPC

- C07D 249/12: Oxygen or sulfur atoms
- C07C 17/18: of oxygen atoms of carbonyl groups
- C07C 45/004: {by reaction with organometalhalides}
- C07C 253/14: by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
- C07C 253/30: by reactions not involving the formation of cyano groups
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present process provides a improved method for the preparation of alkylsulfanyl substituted triazoles 2 which are useful intermediates in a new process for the preparation of triazolones 20.

## Claims

### Claim 1

A process for preparing a compound of formula 2 wherein Ar is phenyl substituted with 2 or 3 groups independently selected from halogen, cyano and C1-6 haloalkyl, Rf is hydrogen, and R1 and R3 are C1-10 alkyl,
which process comprises the steps of:
(a) contacting 4 with a strong base in an inert solvent to form the conjugate base of 4 and contacting said conjugate base with 6 to afford 8;
(b) exposing 8 to conditions which result in hydrolysis of the ester and decarboxylation of the resulting carboxylic acid to afford 2.

### Claim 2 (depends on 1)

A process according to claim 1 wherein Ar is 3-chloro-5-cyano-phenyl, 3,5-dicyano-phenyl or 3-cyano-5-difluoromethyl-phenyl, R1 is methyl and R3 is tert-Bu.

### Claim 3 (depends on 2)

A process according to claim 2 wherein said strong base is potassium tert-butoxide, said inert solvent is THF and said hydrolysis conditions comprise methanesulfonic acid in acetonitrile at reflux temperature.

### Claim 4 (depends on 3)

A process according to claim 3 wherein Ar is 3-cyano-5-difluoromethyl-phenyl.

### Claim 5 (depends on 1)

A process which comprises the steps of claim 1 which process further the steps of:
(a) contacting 2 with a reducing agent capable of selective reduction of the nitro group to afford 12; and,
(b) contacting 12 with a diazotizing reagent and either Cu(I)Br/LiBr or Cu(I)Cl/LiCl to afford 14 wherein R2 is bromo and chloro respectively.

### Claim 6 (depends on 5)

A process according to claim 5 wherein Ar is 3-cyano-5-difluoromethyl-phenyl, R1 is methyl, R2 is bromide, R3 is tert-butyl, said strong base is potassium tert-butoxide, said inert solvent is THF, said hydrolysis conditions comprise methanesulfonic acid in acetonitrile at reflux temperature said reducing agent is hydrogen, Pd/C and VO(acac)2, said diazotizing reagent is tert-butyl nitrite and said cuprous salt is Cu(I)Br.

### Claim 7 (depends on 6)

A process which comprises the steps of claim 6 which process further comprises the step of converting 14 wherein R2 is Br to the tosylate salt.

### Claim 8 (depends on 7)

A process according to claim 7 wherein Ar is 3-cyano-5-difluoromethyl-phenyl, R1 is methyl, R2 is bromide, R3 is tert-butyl, said strong base is potassium tert-butoxide, said inert solvent is THF, said hydrolysis conditions comprise methane sulfonic acid in acetonitrile at reflux temperature said reducing agent is hydrogen Pd/C and VO(acac)2, said diazotizing reagent is tert-butyl nitrite, said cuprous salt is Cu(I)Br and said oxidizing agent is MCBPA.