Synthon B.v.

Synthon IP Inc.

Jiri Bartl

Pavel Slanina

Theodorus H A Peters

Franciscus B G Benneker

Petr Benovsky

Jozef Krajcovic

Frantisek Picha

Marian Buchlovic

Petr Mitas

Lenka Chalupova

Libor Vyklicky

Oldrich Smekal

The presented invention relates to a process for preparation of compound of formula (1) or a salt thereof (i.e.) ozanimod: (1). The invention also relates to intermediates used in the process. 

Process for preparing ozanimod

Synthesis of biphosphonate compounds can be advantageously carried out in a solvent/diluent comprising a compound of formula (3) wherein R is hydrogen or a C1-C6 alkyl group; each of R1 is a C1-C6 alkyl group or both R1 groups are linked to form a C1-C3 alkylene group; and R2 is hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, or is linked together with R to form a C3-C7 carbon ring.

Process for making 1-hydroxyalkylidene-1,1-biphosphonic acids

A 9-hydroxy or 9-acyloxy group can be added to a pyridopyrimidinone ring structure by a process comprising acylating a compound of formula (5) under Vilsmeier-Haack or Friedel-Crafts conditions to form a compound (6); and transforming with a peroxo-compound to obtain the compound (1). R represents hydrogen or a C1-C20 acyl group. The process is useful in the synthesis of paliperidone and derivatives.

Synthesis of paliperidone

A compound of formula (7.2) or an acid addition salt thereof. The compound can be used as a reference standard for monitoring the presence thereof in a paliperidone sample, including monitoring the completion of a paliperidone reaction. Reduction in the amount of the compound in paliperidone can be achieved by crystallization in the presence of a hydride reductant.

Paliperidone ketone

An amantadine salt of montelukast is useful in purification of montelukast or its salts and as a pharmaceutical active ingredient.

Montelukast amantadine salt

The formation of risperidone is enhanced by the use of enriched Z-isomer oxime intermediate(s) of formula (3) or (7). The oxime(s) can be isomerically enriched by a variety of techniques including the use of the novel acetic acid salt thereof, which affords, inter alia, resolution of the isomers and/or by heat conversion.

Process for making risperidone and intermediates therefor

Amlodipine and related analogues thereof are prepared by the following general reaction scheme:Rand Reach independently represent a C-Calkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.

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Strelice, Czechia

Jiri Bartl