Hoffmann-la Roche Inc.

F. Hoffmann-la Roche Ag

Stefan Abrecht

Jean-Michel Adam

Alec Fettes

Patrizio Mattei

Michelangelo Scalone

Beat Wirz

Rudolf Schmid

Urs Schwitter

Ulrich Zutter

Bruno Lohri

Olaf Grassmann

Shaoning Wang

Martin Karpf

Joseph Foricher

Franziska E Rohrer

Francois Montavon

Ren&eacute; Trussardi

Armin Ruf

Gerard Moine

Regina Moog

Andre Bubendorf

Stephan Goetzoe

The present invention relates to a novel process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R, Rand Rare each independently selected from the group consisting of hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy and lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by a group consisting of lower alkoxycarbonyl, aryl and heterocyclyl, and the pharmaceutically acceptable salts thereof. The pyrido[2,1-a]isoquinoline derivatives of the formula I are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

Process for the preparation of pyrido[2,1-a] isoquinoline derivatives

The invention is concerned with (S)-1-{[2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethylamino]-acetyl}-pyrrolidine-2-carbonitrile mesylate and crystalline polymorphs of this compound. This compound and its polymorphic forms exhibits superior properties compared to the previously known compounds and can be used as medicament for the treatment of disorders which are associated with DPP-IV.

Salt and polymorphs of a DPPIV inhibitor

This invention relates to a process of the preparation of the novel intermediate (S)-4-fluoromethyl-dihydro-furan-2-one of the formula and with its use for the manufacture of pyrido[2,1-a]isoquinoline derivatives of the formula which are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one useful in the preparation of the DPP-IV inhibitor (S)-1 ((2S,3S,11bS)-2-amino-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2H-pyrido[2,1-a] isoquinolin-3-yl)-4-fluoromethyl-pyrrolidin-2-one

Process for the preparation for 4,5-diamino shikimic acid derivatives

The invention is concerned with a new process for the preparation of compounds of formula ##STR1## wherein R is hydrogen, lower alkyl, lower alkoxy, cycloalkyl, cycloalkenyl, cycloalkyl-lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl-lower alkyl, heterocyclyl or heterocyclyl-lower alkyl; the lower alkyl, cycloalkyl, lower alkenyl, cycloalkenyl, lower alkynyl, aryl-lower alkyl, aryl and the heterocyclyl moieties being unsubstituted or substituted with at least one group selected from carboxy, amino, carbamoyl, nitro, cyano, lower alkyl, lower alkoxy, hydroxy, halogen, aminomethyl, mercapto, trifluoromethyl and trichloroethyl. The compounds prepared according to above mentioned process are useful in the preparation of cephem, isoxacephem and carbacephem derivatives.

Method for the preparation of .alpha.-Bromo-Lactam derivatives

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Duggingen, Switzerland

Stefan Abrecht