Novartis Ag

Novartis Pharma Gmbh

Gerhard Penn

Benjamin Martin

Florian Karl Kleinbeck-Riniker

Francesco Venturoni

Gottfried Sedelmeier

Thomas Ruch

Bernhard Wietfeld

Thomas Allmendinger

Thierry Schlama

Paolo Filipponi

Philipp Lustenberger

Murat Acemoglu

Beat Schmitz

Maximilian Grassberger

Dierk Wieckhusen

Olivier Lohse

Sabine Pfeffer

Ernst Kuesters

Ulrich Beutler

Ernst K&uuml;sters

Amarylla Horvath

Caspar Vogel

Jean-Paul Mutz

Hanspeter Schilling

Joerg Sedelmeier

Helmut H&auml;cker

Gerhard Fleissner

Otto Hartmann

Cornelia Dosenbach

Ives Mafli

Beat Schmidt

The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.

Process and intermediates

The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril, inter alia via nitro 5 compounds. It further relates to new intermediate compounds and their use for said new chemical synthesis route, as well as a new catalyst ligand.

Processes and intermediates for NEP inhibitor synthesis

The present invention relates to a process for the production of carbamic acid (2-chloroethyl)(3-oxocyclohexyl)-alkyl ester enantiomers and of 1-carbalkoxy-4-ketoperhydroindole enantiomers.

Processes for the preparation of 4-oxo-octahydro-indole-1-carbocyclic acid methyl ester and derivatives thereof

Purification process for the preparation of the allylamine pharmaceutical terbinafine of formula I in free base form or acid addition salt form, by distilling crude terbinafine base, preferably by short path distillation, e.g. at a temperature above 100&#xb0; C. and reduced pressure, e.g. 0.2 mbar, and recovering the purified product in free base or acid addition salt form.

Purification process

The invention relates to a process for preparing 5-(&#x3b1;-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-ones. The process involves (i) reacting (a) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent and a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (b) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent to form 8-acetoxy-(1H)-quinolin-2-one, and treating, in-situ, the 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (c) 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; (ii) reacting the 5-acetyl-8-hydroxy-(1H)-quinolin-2-one prepared in Step (i) with a compound having the Formula RL in the presence of a base and a solvent to form 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one, wherein R is a protecting group and L is a leaving group; and (iii) reacting the 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one with a halogenating agent in the presence of a solvent to form a 5-(&#x3b1;-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one.

Process for the preparation of 5-(halocetyl)-8-(substituted oxy)-(1h)-quinolin-2-ones

Macrolides

Crystalline macrolides and process for their preparation

Growing community of inventors

Oberwil, Switzerland

Gerhard Penn