Pfizer Corporation

Paul Bowles

Dennis Michael Godek

Peter Robert Rose

Frank R Busch

Sabeto A DiRoma

Meldrum Allen

Douglas John

This invention relates to a crystalline form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclo-tetradecine-3-carbonitrile (lorlatinib) free base hydrate (Form). This invention also relates to pharmaceutical compositions comprising Form, and to methods of using Formand such compositions in the treatment of abnormal cell growth, such as cancer, in a mammal.

Crystalline form of lorlatinib free base hydrate

A process for preparing a compounds of the formula ##STR1## or a pharmaceutically acceptable acid addition salt thereof, which comprises reacting a piperazine salt of the formula ##STR2## with an alkyl halide containing compound of the formula ##STR3## in water with a reagent to neutralize the hydrohalic acid and heating the mixture under conditions which are suitable to effect the coupling of said piperazine salt with said alkyl halide containing compound.

Process for preparing aryl piperazinyl-heterocyclic compounds with a

A process for preparing a compounds of the formula ##STR1## or a pharmaceutically acceptable acid addition salt thereof, which comprises reacting a monosubstituted piperazine of the formula ##STR2## with an alkyl halide containing compound of the formula ##STR3## in water with a reagent to neutralize the hydrohalic acid and refluxing the mixture under conditions which are suitable to effect the coupling of said monosubstituted piperazines with said alkyl halide containing compound.

Growing community of inventors

Groton, CT, United States of America

Paul Bowles