Process for the stereoselective preparation of a pyrazole-carboxamide

Patent metadata

Field	Value
Publication number	US-9637457-B2
Application number	US-201414892386-A
Country	US
Kind code	B2
Filing date	Jun 19, 2014
Priority date	Jun 26, 2013
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

The present invention relates to a process for the enantioselective preparation of the compound of formula (Ib), which process comprises a) reducing the (E)- or (Z)-form of a compound of formula (II), with an enantioselective reagent to a compound of formula (IIIa), and b) acylating the compound of formula (IIIa) with the compound of formula (IV), or c) coupling the compound of formula (IV) with the compound of formula (II), to give a compound of formula (V) and d) reducing compound of formula (V) in the presence of hydrogen, a catalyst and a chiral ligand, to the compound of formula (Ib).

First claim

What is claimed is:

1. A process for the enantioselective preparation of the compound of formula (Ib)

which process comprises
a) reducing the (E)- or (Z)-form of a compound of formula (II)

with an enantioselective reagent to give a compound of formula (IIIa)

and
b) acylating the compound of formula (IIIa) with the compound of formula (IV)

or
c) coupling the compound of formula (IV) with the compound of formula (II), to give a compound of formula (V)

and
d) reducing the compound of formula (V) in the presence of hydrogen, a catalyst and a chiral ligand, to give the compound of formula (Ib).

2. The process for the enantioselective preparation of the compound of formula (Ib) according to claim 1 , which process comprises
a) reducing the (E)- or (Z)-form of a compound of formula (II)

with an enantioselective reagent to a compound of formula (IIIa)

and
b) acylating the compound of formula (IIIa) with the compound of formula (IV)

3. The process for the enantioselective preparation of the compound of formula (Ib) according to claim 1 , which process comprises
c) coupling the compound of formula (IV) with the compound of formula (II), to give a compound of formula (V)

and
d) reducing the compound of formula (V) in the presence of hydrogen, a catalyst and a chiral ligand, to the compound of formula (Ib).

4. The process for the enantioselective preparation of the compound of formula (Ib) according to claim 1 ,

which process comprises
a) reducing the (E)- or (Z)-form of a compound of formula (II)

with a borane complex as a reducing agent, in the presence of a single enantiomer of a chiral 1,2-amino-alcohol, in an inert solvent and at temperatures ranging from 0° C. and 60° C., to a compound of formula (IIIa)

and
b) acylating the compound of formula (IIIa) with the compound of formula (IV), in an inert solvent, in the presence of a weak base and at temperatures ranging between −20° C. and 120° C.

or
c) coupling the compound of formula (IV) with the compound of formula (II), by deprotonation of compound of formula (II) with 1 to 5 equivalents of a suitable base in an inert aprotic solvent, wherein the suitable base is selected from KN(iPr) 2 , LiN(iPr) 2 , KN(trimethylsilyl) 2 , BuLi, and KN(iPr) 2 /KOtBu, at temperature ranging from −78° C. to 25° C., followed by treatment with compound of formula (IV), to give a compound of formula (V),

and
d) reducing the compound of formula (V) in the presence of hydrogen at pressures ranging from 0.1 bar to 15 MPa, in the presence of 0.1 to 0.0001 equivalent of a metal catalyst and a single enantiomer of a suitable chiral ligand, in ratio of metal catalyst to chiral ligand ranging from 0.8 to 1.5, in a suitable solvent and at temperatures ranging from 20° C. to 100° C., to give the compound of formula (Ib).

5. The compound of formula (V)

6. The process of claim 2 , wherein the reduction of the compound of formula (II) is performed via the action of borane in the presence of a single enantiomer of a chiral amino-alcohol.

7. The process according to claim 6 , wherein the source of borane is borane diethylaniline.

Assignees

• Syngenta Participations Ag

Inventors

• Dumeunier Raphael
• Kessabi Jilali
• Wendeborn Sebastian Volker
• Nussbaumer Hannes

Classifications

• C07D231/14 Primary

  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

• C07C239/20

  having oxygen atoms of hydroxylamino groups etherified · CPC title