Acerta Pharma B.v.

Lucinda Victoria Jackson

Katie Grace Cooper

Angang Wang

Paul Allen Bethel

David Allen Short

Qiu Junying

Rustam Ferdinand Garrey

Michael Joseph Lawler

Kirsty Jane Millard

Alexander James Telford

Andrew John Phillips

Robert John Cox

Shaun Alan Hughes

Michael David Golden

Lai Chun Chan

Jerry B Evarts

Frank L M Vos

Eric Jurriën Zijp

Remy E J N Litjens

Peter Johannes Servaas Savio Van Eijk

Mathilda Maria Henrica Verstappen

Mark Andrew Graham

David Pranay Dave

Phillip Anthony Inglesby

Gary Michael Noonan

The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.

Processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)-pyrrolidin-2-yljimidazo[1,5-a]-pyrazin-1-yl}n-(pyridin-2-yl)-benzamide

The present disclosure concerns the large-scale manufacture of pharmaceutical compounds, and novel intermediates for use in the manufacture. International Patent Application WO2011154737 discloses morpholine pyrimidines useful for treating cancer, processes for their preparation and pharmaceutical compositions thereof. In particular, WO2011154737 discloses, as experimental Example 2.02 on page 60, the compound 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)—S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (hereafter referred to as the compound of Formula (I)). The structure of the compound of Formula (I) is shown below. A synthetic route to the compound of Formula (I) is described at pages 51 to 57, 66 and 67 of WO2011154737, and is summarised below in Scheme 1.

Pharmaceutical process for the preparation of 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)-S-methylsulfonimidoyl) cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b] pyridine and intermediates

Processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)-pyrrolidin-2-yl]imidazo[1,5-a]-pyrazin-1-yl}N-(pyridin-2-yl)-benzamide

Growing community of inventors

Cambridge, United Kingdom

Lucinda Victoria Jackson