Novartis Ag

Novartis Pharma Gmbh

Olivier Lohse

Mahavir Prashad

Daniel Kaufmann

Bin Hu

Gerhard Penn

Werner Zaugg

Ulrich Beutler

Hanspeter Schilling

Caspar Vogel

Jean-Louis Reber

Peter Funfschilling

Peter Fünfschilling

Compounds of formula I in salt or solvate form, wherein W, R, R, R, R, R, R, R, Rand Rand A have the meanings as indicated in the specification, are useful for treating diseases mediated by the &#x3b2;-adrenoreceptor. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

Quinolinone derivatives and their pharmaceutical compositions

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

A process for preparing 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8- hydroxy-(1H)-quinolin-2-one salt. The process involves forming an acid salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-substituted oxy-(1H)-quinolin-2-one; and converting the acid salt to a salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one without isolating the free base of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one.

Process for preparing 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one salt, useful as an andrenoceptor agonist

The invention relates to new processes for the preparation of the pharmaceutical oxcarbazepine, as well as novel intermediates prepared by or used for said processes, and the preparation of said intermediates.

Dibenzo [b,f]azepine intermediates

A process for preparing 5,6-diethyl-2,3-dihydro-1H-inden-2-amine and acid addition salts thereof from 2-aminoindan. The process comprises protecting the amino group of 2-aminoindan, acetylating the ring in the protected compound, reducing the acetyl group to ethyl to form a monoethyl derivative, acetylating the monoethyl derivative, reducing the acetyl group to form a diethyl derivative, deprotecting the latter by hydrolysis and recovering the product in free or salt form. The process does not use deleterious Grignard reagents or nitrites such as isoamyl nitrite, and provides high regioselectivity and high yield of 5,6-diethyl-2,3-dihydro-1H-inden-2-amine. In addition, the process uses acetyl halide as both a reactant and a solvent.

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Rixheim, France

Olivier Lohse