Synthon B.v.

Petr Benovsky

Jie Zhu

Lambertus Thijs

Arjanne Overeem

Radomir Skoumal

Jakub Castulik

Petr Bartos

Jiri Bartl

Jozef Krajcovic

Jiri Barti

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

A compound of the following formula wherein R' is a straight or branched C1-C4 alkyl group is useful in processes associated with the synthesis of montelukast and its salts.

Process for making montelukast and intermediates therefor

The reaction of methylmagnesium halide is improved by the presence of a cerium (III) salt such as cerium trichloride. The reactions are typically associated with the production of montelukast, a pharmaceutically useful compound of the following formula and salts thereof. Further enhancements can be derived from certain intermediates, salts thereof and/or purification thereof before and/or after the reaction involving methylmagnesium halide.

A process for making montelukast, a pharmaceutically useful compound of the following formula and salts thereof: using a compound of formula (11) is provided.

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Brno, Czechia

Petr Benovsky