Dsm Sinochem Pharmaceuticals Netherlands B.v.

Dsm IP Assets B.v.

Centrient Pharmaceuticals Netherlands B.v.

Dennis Heemskerk

Ben De Lange

Karin Henderika Maria Bessembinder

Daniel Mink

Harold Monro Moody

Michael Wolberg

Theodorus Johannes Godfried Maria Van Dooren

Wilhelmus Hubertus Joseph Boesten

Sven Panke

Peter Hans Riebel

Georgios Sarakinos

Anja Gerarda Margaretha Hogenboom

Carlos Enrique Lenhardt

Joannes Gerardus Kierkels

Franciscus Alphons Lommen

Van Theodorus Johannes Godfried Maria Dooren

De Ben Lange

The present invention relates to a process for preparing a statin precursor, which process comprises a first reaction step, wherein a hydroxy-pyrimidine-carbonitrile is reacted with an organic sulfonyl halide to form the sulfonate-pyrimidine-carbonitrile; a second reaction step, wherein the sulfonate-pyrimidine-carbonitrile is reacted with N-methylmethane sulfonamide to form a pyrimidinyl-sulfonamide; and optionally a third reaction step, wherein the pyrimidinyl-sulfonamide is reacted with a reducing agent. All steps are conducted in toluene as the main solvent.

Process for preparing statin precursor

The present invention relates to a process for the preparation of a precursor for the synthesis of hexanoic acid derived statins and to the use of said precursor in the manufacture of a medicament.

Process for the preparation of a thioprecursor for statins

The present invention relates to a process for the preparation of a diol sulfone derivative comprising reaction of a halomethyl substrate with a thio-aryl compound to obtain a thio-ether compound, and oxidizing the thio-ether compound to the corresponding sulfone. In case of a chiral halomethyl substrate, the resulting chiral diol sulfone derivative is suitable as a building block for statin type compounds.

Process for the preparation of diol sulfones

The present invention relates to a process for the preparation of statins by means of a Julia-Kocienski reaction between an aldehyde and a sulfone derivative in the presence of an alkaline metal alkoxy base. The resulting derivatives are suitable as building blocks for statin type compounds such as cerivastatin, fluvastatin, pitavastatin and rosuvastatin.

Process for the preparation of statins in the presence of base

Process for the preparation of a statin precursor

The present invention relates to 5-substituted hydantoins, a process for the preparation of 5-substituted hydantoins and the use of 5-substituted hydantoins in the preparation of enantiomerically enriched &#x3b1;-amino acids. Furthermore, the present invention relates to the preparation of pharmaceutically active products such as perindopril and ramipril using the novel 5-substituted hydantoins.

5 substituted hydantoins

The present invention relates to a process for the preparation of octahydrocyclopenta[b]pyrrole-2-carboxylic acid and esters thereof of general formula (1) in the presence of a cobalt and/or nickel comprising catalyst and to the use of compounds of general formula (1) in the synthesis of ramipril. 

Method for the synthesis of a ramipril intermediate

The present invention describes a process for preparing cephradine, said process comprising reacting 7-aminodesacetoxy cephalosporanic acid (7-ADCA) with D-dihydrophenylglycine in activated form (DHa) in the presence of an enzyme in a reaction mixture to form cephradine, resulting in a conversion of 7-ADCA into cephradine of at least 70%, wherein the concentration D-dihydrophenylglycine (DH) in the reaction mixture is below 2 wt.%, wherein the conversion of 7-ADCA into cephradine & equals; (n/n)*100%, wherein n=quantity of cephradine formed (in mole); and n=total quantity of 7-ADCA added to reaction mixture (in mole). The invention also describes a process for the preparation of cephradine hydrate characterised in that the process comprises: &#x2014;reacting 7-amino acid desacetoxy cephalosporanic acid (7-ADCA) with DHa in the presence of an enzyme in a reaction mixture to form cephradine; &#x2014;preparing an aqueous solution comprising at least part of the cephradine; and crystallising the cephradine from said aqueous solution. The invention further describes cephradine hydrate obtainable by a process according to invention. The invention also describes cephradine hydrate with an absorbance at 450 nm of below 0.050.

Process for the preparation of cephradine

The invention relates to a process for the preparation of a 2,4-dideoxyhexose or a 2,4,6-trideoxyhexose from a substituted or unsubstituted carbonyl compound with at least 2 carbon atoms and at least one &#x3b1;-hydrogen atom and a substituted or unsubstituted aldehyde in the presence of an aldolase and water, the reaction between the substituted or unsubstituted carbonyl compound with at least 2 carbon atoms and at least one &#x3b1;-hydrogen atom and the substituted or unsubstituted aldehyde being carried out at a carbonyl concentration of at most 6 moles/l of reaction mixture and the final concentration of the 2,4-dideoxyhexose or the 2,4,6-trideoxyhexose being at least 2 mass % of the reaction mixture. The invention also relates to the use of a 2,4-dideoxyhexose or a 2,4,6-trideoxyhexose obtained by means of a process according to the invention in the preparation of a medicine, particularly in the preparation of a statine.

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