US 2009/0023903 A1Published application

Process for the preparation of trifluoroalkyl-phenyl and heterocyclic sulfonamides

AssigneeWyeth

InventorsTerrence Joseph Connolly, Anita Wai-Yin Chan, Zhixian Ding, Mousumi Ghosh, Xinxu Shi, Jianxin Ren, Eric Hansen, Roger Farr, Michael MacEwan, Asaf Alimardanov, Antonia Nikitenko, John Potoski

Life of this patent

Estimating the term…

patentgrep

Loading patent…

Abstract

A novel trifluoroacetylating agent, i.e., N-trifluoroacetylmorpholine, is described. This reagent is useful in the preparation of phenyl and heterocyclic sulfonamide compounds. Methods are therefore described for preparing sulfonamide compounds of the following structure, wherein R1 and R2 are defined herein, using N-trifluoroacetylmorpholine. The sulfonamide compounds that may be prepared as described herein include 5-chloro-thiophene-2-sulfonic acid [(1S,2R)-2-(3,5-difluoro-phenyl)-3,3,3-trifluoro-1-hydroxymethyl-propyl]-amide using N-trifluoroacetylmorpholine.

Claims35

Dependent claims

A method for preparing a sulfonamide compound of the structure:

wherein:
R1 is selected from the group consisting of C1 to C10 alkyl, C1 to C10 substituted alkyl, C3 to C8 cycloalkyl, C3 to C8 substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
R2 is aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
said method comprising:
(a) reacting trifluoroacetic anhydride, morpholine, and a proton scavenger to form N-trifluoroacetylmorpholine;
(b) reacting N-trifluoroacetylmorpholine with R1MgX or R1Li to form R1C(O)CF3;
wherein, X is Br, Cl, or I;
(c) condensing R1C(O)CF3 with a phosphonoacetate reagent;
(d) hydrolyzing the product of step (c) to form R1C(CF3)═CHCO2H;
(e) converting R1C(CF3)═CHCO2H to a mixed anhydride;
(f) reacting said mixed anhydride with a chiral auxiliary compound;
(g) reducing the product of step (f);
(h) converting the product of step (g) to an azide;
(i) converting said azide to an amine salt;
(j) reducing said amine hydrochloride salt to an amino alcohol salt of the structure:
(k) reacting said amino alcohol salt with R2SO2LG;
wherein LG is a leaving group.

14 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/172,486Filed 14 Jul 2008
Priority: 16 Jul 2007
Published: 22 Jan 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 295/108
With the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by…: to an…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07D 263/26
Attached in position 2: with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
C07D 333/34
Hetero atoms other than halogen: sulfur atoms